Difference between revisions of "Non-small cell lung cancer, EGFR-mutated"
Warner-admin (talk | contribs) |
m (Text replacement - "style="background-color:#1a9851" |Phase III" to "style="background-color:#1a9851" |Phase 3") |
||
Line 29: | Line 29: | ||
|[https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(17)30729-5/fulltext Zhong et al. 2017 (ADJUVANT/CTONG1104)] | |[https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(17)30729-5/fulltext Zhong et al. 2017 (ADJUVANT/CTONG1104)] | ||
|2011-2014 | |2011-2014 | ||
− | | style="background-color:#1a9851" |Phase | + | | style="background-color:#1a9851" |Phase 3 (C) |
|[[#Gefitinib_monotherapy|Gefinitib]] | |[[#Gefitinib_monotherapy|Gefinitib]] | ||
| style="background-color:#d73027" |Inferior DFS | | style="background-color:#d73027" |Inferior DFS | ||
Line 69: | Line 69: | ||
|[https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(17)30729-5/fulltext Zhong et al. 2017 (ADJUVANT/CTONG1104)] | |[https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(17)30729-5/fulltext Zhong et al. 2017 (ADJUVANT/CTONG1104)] | ||
|2011-2014 | |2011-2014 | ||
− | | style="background-color:#1a9851" |Phase | + | | style="background-color:#1a9851" |Phase 3 (E-switch-ooc) |
|[[#Cisplatin_.26_Vinorelbine|Cisplatin & Vinorelbine]] | |[[#Cisplatin_.26_Vinorelbine|Cisplatin & Vinorelbine]] | ||
| style="background-color:#1a9850" |Superior DFS<br>Median DFS: 28.7 vs 18 mo<br>(HR 0.60, 95% CI 0.42-0.87) | | style="background-color:#1a9850" |Superior DFS<br>Median DFS: 28.7 vs 18 mo<br>(HR 0.60, 95% CI 0.42-0.87) | ||
Line 108: | Line 108: | ||
|[https://doi.org/10.1016/s2213-2600(21)00134-x He et al. 2021 (EVIDENCE)] | |[https://doi.org/10.1016/s2213-2600(21)00134-x He et al. 2021 (EVIDENCE)] | ||
|2015-2019 | |2015-2019 | ||
− | | style="background-color:#1a9851" |Phase | + | | style="background-color:#1a9851" |Phase 3 (E-switch-ooc) |
|1. [[#Cisplatin_.26_Pemetrexed|Cisplatin & Pemetrexed]]<br>2. [[#Cisplatin_.26_Vinorelbine|Cisplatinb & Vinorelbine]] | |1. [[#Cisplatin_.26_Pemetrexed|Cisplatin & Pemetrexed]]<br>2. [[#Cisplatin_.26_Vinorelbine|Cisplatinb & Vinorelbine]] | ||
| style="background-color:#1a9850" |Superior DFS<br>Median DFS: 47 vs 22.1 mo<br>(HR 0.36, 95% CI 0.24-0.55) | | style="background-color:#1a9850" |Superior DFS<br>Median DFS: 47 vs 22.1 mo<br>(HR 0.36, 95% CI 0.24-0.55) | ||
Line 147: | Line 147: | ||
|[https://doi.org/10.1056/nejmoa2027071 Wu et al. 2020 (ADAURA)] | |[https://doi.org/10.1056/nejmoa2027071 Wu et al. 2020 (ADAURA)] | ||
|2015-2019 | |2015-2019 | ||
− | | style="background-color:#1a9851" |Phase | + | | style="background-color:#1a9851" |Phase 3 (E-RT-esc) |
|Placebo | |Placebo | ||
| style="background-color:#1a9850" |Superior DFS<br>DFS24: 90% vs 44%<br>(HR 0.17, 99.06% CI 0.11-0.26) | | style="background-color:#1a9850" |Superior DFS<br>DFS24: 90% vs 44%<br>(HR 0.17, 99.06% CI 0.11-0.26) | ||
Line 293: | Line 293: | ||
|[https://doi.org/10.1200/jco.2012.44.2806 Sequist et al. 2013 (LUX-Lung 3)] | |[https://doi.org/10.1200/jco.2012.44.2806 Sequist et al. 2013 (LUX-Lung 3)] | ||
|2009-2011 | |2009-2011 | ||
− | | style="background-color:#1a9851" |Phase | + | | style="background-color:#1a9851" |Phase 3 (E-RT-switch-ooc) |
|[[#Cisplatin_.26_Pemetrexed|Cisplatin & Pemetrexed]] | |[[#Cisplatin_.26_Pemetrexed|Cisplatin & Pemetrexed]] | ||
| style="background-color:#1a9850" |Superior PFS | | style="background-color:#1a9850" |Superior PFS | ||
Line 299: | Line 299: | ||
|[https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(13)70604-1/fulltext Wu et al. 2014 (LUX-Lung 6)] | |[https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(13)70604-1/fulltext Wu et al. 2014 (LUX-Lung 6)] | ||
|2010-2011 | |2010-2011 | ||
− | | style="background-color:#1a9851" |Phase | + | | style="background-color:#1a9851" |Phase 3 (E-RT-switch-ooc) |
|[[#Cisplatin_.26_Gemcitabine_.28GC.29|Cisplatin & Gemcitabine]] | |[[#Cisplatin_.26_Gemcitabine_.28GC.29|Cisplatin & Gemcitabine]] | ||
| style="background-color:#1a9850" |Superior PFS | | style="background-color:#1a9850" |Superior PFS | ||
Line 355: | Line 355: | ||
|[https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(11)70393-X/fulltext Rossell et al. 2012 (EURTAC)] | |[https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(11)70393-X/fulltext Rossell et al. 2012 (EURTAC)] | ||
|2007-2011 | |2007-2011 | ||
− | | style="background-color:#1a9851" |Phase | + | | style="background-color:#1a9851" |Phase 3 (C) |
|[[#Erlotinib_monotherapy|Erlotinib]] | |[[#Erlotinib_monotherapy|Erlotinib]] | ||
| style="background-color:#d73027" |Inferior PFS | | style="background-color:#d73027" |Inferior PFS | ||
Line 393: | Line 393: | ||
|[https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(11)70393-X/fulltext Rossell et al. 2012 (EURTAC)] | |[https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(11)70393-X/fulltext Rossell et al. 2012 (EURTAC)] | ||
|2007-2011 | |2007-2011 | ||
− | | style="background-color:#1a9851" |Phase | + | | style="background-color:#1a9851" |Phase 3 (C) |
|[[#Erlotinib_monotherapy|Erlotinib]] | |[[#Erlotinib_monotherapy|Erlotinib]] | ||
| style="background-color:#d73027" |Inferior PFS | | style="background-color:#d73027" |Inferior PFS | ||
Line 399: | Line 399: | ||
|[https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(11)70184-X/fulltext Zhou et al. 2011 (CTONG-0802)] | |[https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(11)70184-X/fulltext Zhou et al. 2011 (CTONG-0802)] | ||
|2008-2009 | |2008-2009 | ||
− | | style="background-color:#1a9851" |Phase | + | | style="background-color:#1a9851" |Phase 3 (C) |
|[[#Erlotinib_monotherapy|Erlotinib]] | |[[#Erlotinib_monotherapy|Erlotinib]] | ||
| style="background-color:#d73027" |Inferior PFS | | style="background-color:#d73027" |Inferior PFS | ||
Line 436: | Line 436: | ||
|[https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(13)70254-7/fulltext Wu et al. 2013 (FASTACT-2)] | |[https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(13)70254-7/fulltext Wu et al. 2013 (FASTACT-2)] | ||
|2009-2010 | |2009-2010 | ||
− | | style="background-color:#1a9851" |Phase | + | | style="background-color:#1a9851" |Phase 3 (E-esc) |
|[[#Carboplatin_.26_Gemcitabine_.28GCb.29|Carboplatin & Gemcitabine]] | |[[#Carboplatin_.26_Gemcitabine_.28GCb.29|Carboplatin & Gemcitabine]] | ||
| style="background-color:#91cf60" |Seems to have superior OS | | style="background-color:#91cf60" |Seems to have superior OS | ||
Line 474: | Line 474: | ||
|[https://www.nejm.org/doi/full/10.1056/NEJMoa0909530 Maemondo et al. 2010 (NEJ002)] | |[https://www.nejm.org/doi/full/10.1056/NEJMoa0909530 Maemondo et al. 2010 (NEJ002)] | ||
|2006-2009 | |2006-2009 | ||
− | | style="background-color:#1a9851" |Phase | + | | style="background-color:#1a9851" |Phase 3 (C) |
|[[#Gefitinib_monotherapy_2|Gefitinib]] | |[[#Gefitinib_monotherapy_2|Gefitinib]] | ||
| style="background-color:#d73027" |Inferior PFS | | style="background-color:#d73027" |Inferior PFS | ||
Line 509: | Line 509: | ||
|[https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(11)70393-X/fulltext Rossell et al. 2012 (EURTAC)] | |[https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(11)70393-X/fulltext Rossell et al. 2012 (EURTAC)] | ||
|2007-2011 | |2007-2011 | ||
− | | style="background-color:#1a9851" |Phase | + | | style="background-color:#1a9851" |Phase 3 (C) |
|[[#Erlotinib_monotherapy|Erlotinib]] | |[[#Erlotinib_monotherapy|Erlotinib]] | ||
| style="background-color:#d73027" |Inferior PFS | | style="background-color:#d73027" |Inferior PFS | ||
Line 532: | Line 532: | ||
|[https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(09)70364-X/fulltext Mitsudomi et al. 2009 (WJTOG3405)] | |[https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(09)70364-X/fulltext Mitsudomi et al. 2009 (WJTOG3405)] | ||
|2006-2009 | |2006-2009 | ||
− | | style="background-color:#1a9851" |Phase | + | | style="background-color:#1a9851" |Phase 3 (C) |
|[[#Gefitinib_monotherapy_2|Gefitinib]] | |[[#Gefitinib_monotherapy_2|Gefitinib]] | ||
| style="background-color:#d73027" |Inferior PFS | | style="background-color:#d73027" |Inferior PFS | ||
Line 567: | Line 567: | ||
|[https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(13)70604-1/fulltext Wu et al. 2014 (LUX-Lung 6)] | |[https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(13)70604-1/fulltext Wu et al. 2014 (LUX-Lung 6)] | ||
|2010-2011 | |2010-2011 | ||
− | | style="background-color:#1a9851" |Phase | + | | style="background-color:#1a9851" |Phase 3 (C) |
|[[#Afatinib_monotherapy|Afatinib]] | |[[#Afatinib_monotherapy|Afatinib]] | ||
| style="background-color:#d73027" |Inferior PFS | | style="background-color:#d73027" |Inferior PFS | ||
Line 590: | Line 590: | ||
|[https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(11)70393-X/fulltext Rossell et al. 2012 (EURTAC)] | |[https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(11)70393-X/fulltext Rossell et al. 2012 (EURTAC)] | ||
|2007-2011 | |2007-2011 | ||
− | | style="background-color:#1a9851" |Phase | + | | style="background-color:#1a9851" |Phase 3 (C) |
|[[#Erlotinib_monotherapy|Erlotinib]] | |[[#Erlotinib_monotherapy|Erlotinib]] | ||
| style="background-color:#d73027" |Inferior PFS | | style="background-color:#d73027" |Inferior PFS | ||
Line 596: | Line 596: | ||
|[https://doi.org/10.1093/annonc/mdv270 Wu et al. 2015 (ENSURE)] | |[https://doi.org/10.1093/annonc/mdv270 Wu et al. 2015 (ENSURE)] | ||
|2011-2012 | |2011-2012 | ||
− | | style="background-color:#1a9851" |Phase | + | | style="background-color:#1a9851" |Phase 3 (C) |
|[[#Erlotinib_monotherapy|Erlotinib]] | |[[#Erlotinib_monotherapy|Erlotinib]] | ||
| style="background-color:#d73027" |Inferior PFS | | style="background-color:#d73027" |Inferior PFS | ||
Line 633: | Line 633: | ||
|[https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(13)70254-7/fulltext Wu et al. 2013 (FASTACT-2)] | |[https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(13)70254-7/fulltext Wu et al. 2013 (FASTACT-2)] | ||
|2009-2010 | |2009-2010 | ||
− | | style="background-color:#1a9851" |Phase | + | | style="background-color:#1a9851" |Phase 3 (E-esc) |
|[[Non-small_cell_lung_cancer#Cisplatin_.26_Gemcitabine_.28GC.29_2|Cisplatin & Gemcitabine]] | |[[Non-small_cell_lung_cancer#Cisplatin_.26_Gemcitabine_.28GC.29_2|Cisplatin & Gemcitabine]] | ||
| style="background-color:#91cf60" |Seems to have superior OS | | style="background-color:#91cf60" |Seems to have superior OS | ||
Line 674: | Line 674: | ||
|[https://doi.org/10.1200/jco.2012.44.2806 Sequist et al. 2013 (LUX-Lung 3)] | |[https://doi.org/10.1200/jco.2012.44.2806 Sequist et al. 2013 (LUX-Lung 3)] | ||
|2009-2011 | |2009-2011 | ||
− | | style="background-color:#1a9851" |Phase | + | | style="background-color:#1a9851" |Phase 3 (C) |
|[[#Afatinib_monotherapy|Afatinib]] | |[[#Afatinib_monotherapy|Afatinib]] | ||
| style="background-color:#d73027" |Inferior PFS | | style="background-color:#d73027" |Inferior PFS | ||
Line 680: | Line 680: | ||
|[https://doi.org/10.1093/annonc/mdx359 Shi et al. 2017 (CONVINCE)] | |[https://doi.org/10.1093/annonc/mdx359 Shi et al. 2017 (CONVINCE)] | ||
|2013-2014 | |2013-2014 | ||
− | | style="background-color:#1a9851" |Phase | + | | style="background-color:#1a9851" |Phase 3 (C) |
|[[Complex_multipart_regimens#CONVINCE|See link]] | |[[Complex_multipart_regimens#CONVINCE|See link]] | ||
| style="background-color:#d73027" |[[Complex_multipart_regimens#CONVINCE|See link]] | | style="background-color:#d73027" |[[Complex_multipart_regimens#CONVINCE|See link]] | ||
Line 737: | Line 737: | ||
|[https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(14)70452-8/abstract Ramalingam et al. 2014 (ARCHER 1009)] | |[https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(14)70452-8/abstract Ramalingam et al. 2014 (ARCHER 1009)] | ||
|2011-2013 | |2011-2013 | ||
− | | style="background-color:#1a9851" |Phase | + | | style="background-color:#1a9851" |Phase 3 (E-switch-ic) |
|[[#Erlotinib_monotherapy|Erlotinib]] | |[[#Erlotinib_monotherapy|Erlotinib]] | ||
| style="background-color:#ffffbf" |Did not meet primary endpoint of PFS<br>Median PFS: 2.6 vs 2.6 mo<br>(HR 0.94, 95% CI 0.80-1.10) | | style="background-color:#ffffbf" |Did not meet primary endpoint of PFS<br>Median PFS: 2.6 vs 2.6 mo<br>(HR 0.94, 95% CI 0.80-1.10) | ||
Line 743: | Line 743: | ||
|[https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(17)30608-3/fulltext Wu et al. 2017 (ARCHER 1050)] | |[https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(17)30608-3/fulltext Wu et al. 2017 (ARCHER 1050)] | ||
|2013-2015 | |2013-2015 | ||
− | | style="background-color:#1a9851" |Phase | + | | style="background-color:#1a9851" |Phase 3 (E-RT-switch-ic) |
|[[#Gefitinib_monotherapy_2|Gefitinib]] | |[[#Gefitinib_monotherapy_2|Gefitinib]] | ||
| style="background-color:#91cf60" |Seems to have superior OS<sup>1</sup><br>Median OS: 34.1 vs 27 mo<br>(HR 0.75, 95% CI 0.59-0.95) | | style="background-color:#91cf60" |Seems to have superior OS<sup>1</sup><br>Median OS: 34.1 vs 27 mo<br>(HR 0.75, 95% CI 0.59-0.95) | ||
Line 786: | Line 786: | ||
|[https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(11)70393-X/fulltext Rossell et al. 2012 (EURTAC)] | |[https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(11)70393-X/fulltext Rossell et al. 2012 (EURTAC)] | ||
|2007-2011 | |2007-2011 | ||
− | | style="background-color:#1a9851" |Phase | + | | style="background-color:#1a9851" |Phase 3 (E-RT-switch-ooc) |
|1. [[#Carboplatin_.26_Docetaxel|Carboplatin & Docetaxel]]<br> 2. [[#Carboplatin_.26_Gemcitabine_.28GCb.29|Carboplatin & Gemcitabine]]<br> 3. [[#Cisplatin_.26_Docetaxel_.28DC.29|Cisplatin & Docetaxel]]<br> 4. [[#Cisplatin_.26_Gemcitabine_.28GC.29|Cisplatin & Gemcitabine]] | |1. [[#Carboplatin_.26_Docetaxel|Carboplatin & Docetaxel]]<br> 2. [[#Carboplatin_.26_Gemcitabine_.28GCb.29|Carboplatin & Gemcitabine]]<br> 3. [[#Cisplatin_.26_Docetaxel_.28DC.29|Cisplatin & Docetaxel]]<br> 4. [[#Cisplatin_.26_Gemcitabine_.28GC.29|Cisplatin & Gemcitabine]] | ||
| style="background-color:#1a9850" |Superior PFS<br>Median PFS: 9.7 vs 5.2 mo<br>(HR 0.37, 95% CI 0.25-0.54) | | style="background-color:#1a9850" |Superior PFS<br>Median PFS: 9.7 vs 5.2 mo<br>(HR 0.37, 95% CI 0.25-0.54) | ||
Line 792: | Line 792: | ||
|[https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(11)70184-X/fulltext Zhou et al. 2011 (CTONG-0802)] | |[https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(11)70184-X/fulltext Zhou et al. 2011 (CTONG-0802)] | ||
|2008-2009 | |2008-2009 | ||
− | | style="background-color:#1a9851" |Phase | + | | style="background-color:#1a9851" |Phase 3 (E-switch-ooc) |
|[[#Carboplatin_.26_Gemcitabine_.28GCb.29|Carboplatin & Gemcitabine]] | |[[#Carboplatin_.26_Gemcitabine_.28GCb.29|Carboplatin & Gemcitabine]] | ||
| style="background-color:#1a9850" |Superior PFS<br>Median PFS: 13.1 vs 4.6 mo<br>(HR 0.16, 95% CI 0.10-0.26) | | style="background-color:#1a9850" |Superior PFS<br>Median PFS: 13.1 vs 4.6 mo<br>(HR 0.16, 95% CI 0.10-0.26) | ||
Line 804: | Line 804: | ||
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5344291/ Yang et al. 2017 (CTONG 0901)] | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5344291/ Yang et al. 2017 (CTONG 0901)] | ||
|2009-2014 | |2009-2014 | ||
− | | style="background-color:#1a9851" |Phase | + | | style="background-color:#1a9851" |Phase 3 (C) |
|[[#Gefitinib_monotherapy_2|Gefitinib]] | |[[#Gefitinib_monotherapy_2|Gefitinib]] | ||
| style="background-color:#ffffbf" |Did not meet primary endpoint of PFS | | style="background-color:#ffffbf" |Did not meet primary endpoint of PFS | ||
Line 816: | Line 816: | ||
|[https://doi.org/10.1093/annonc/mdv270 Wu et al. 2015 (ENSURE)] | |[https://doi.org/10.1093/annonc/mdv270 Wu et al. 2015 (ENSURE)] | ||
|2011-2012 | |2011-2012 | ||
− | | style="background-color:#1a9851" |Phase | + | | style="background-color:#1a9851" |Phase 3 (E-switch-ooc) |
|[[#Cisplatin_.26_Gemcitabine_.28GC.29|Cisplatin & Gemcitabine]] | |[[#Cisplatin_.26_Gemcitabine_.28GC.29|Cisplatin & Gemcitabine]] | ||
| style="background-color:#1a9850" |Superior PFS<br>Median PFS: 11.0 vs 5.5 mo<br>(HR 0.34, 95% CI 0.22-0.51) | | style="background-color:#1a9850" |Superior PFS<br>Median PFS: 11.0 vs 5.5 mo<br>(HR 0.34, 95% CI 0.22-0.51) | ||
Line 822: | Line 822: | ||
|[https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(14)70452-8/abstract Ramalingam et al. 2014 (ARCHER 1009)] | |[https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(14)70452-8/abstract Ramalingam et al. 2014 (ARCHER 1009)] | ||
|2011-2013 | |2011-2013 | ||
− | | style="background-color:#1a9851" |Phase | + | | style="background-color:#1a9851" |Phase 3 (C) |
|[[#Dacomitinib_monotherapy|Dacomitinib]] | |[[#Dacomitinib_monotherapy|Dacomitinib]] | ||
| style="background-color:#ffffbf" |Did not meet primary endpoint of PFS | | style="background-color:#ffffbf" |Did not meet primary endpoint of PFS | ||
Line 828: | Line 828: | ||
|[https://www.nejm.org/doi/full/10.1056/NEJMoa1713137 Soria et al. 2017 (FLAURA)] | |[https://www.nejm.org/doi/full/10.1056/NEJMoa1713137 Soria et al. 2017 (FLAURA)] | ||
|2014-2016 | |2014-2016 | ||
− | | style="background-color:#1a9851" |Phase | + | | style="background-color:#1a9851" |Phase 3 (C) |
|[[#Osimertinib_monotherapy_2|Osimertinib]] | |[[#Osimertinib_monotherapy_2|Osimertinib]] | ||
| style="background-color:#fc8d59" |Seems to have inferior OS<sup>1</sup> | | style="background-color:#fc8d59" |Seems to have inferior OS<sup>1</sup> | ||
Line 834: | Line 834: | ||
|[https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(19)30035-X/fulltext Saito et al. 2019 (NEJ026)] | |[https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(19)30035-X/fulltext Saito et al. 2019 (NEJ026)] | ||
|2015-2016 | |2015-2016 | ||
− | | style="background-color:#1a9851" |Phase | + | | style="background-color:#1a9851" |Phase 3 (C) |
|[[#Erlotinib_.26_Bevacizumab|Erlotinib & Bevacizumab]] | |[[#Erlotinib_.26_Bevacizumab|Erlotinib & Bevacizumab]] | ||
| style="background-color:#fc8d59" |Seems to have inferior PFS | | style="background-color:#fc8d59" |Seems to have inferior PFS | ||
Line 840: | Line 840: | ||
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6736319/ Kelly et al. 2019 (SOLAR<sub>NSCLC</sub>)] | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6736319/ Kelly et al. 2019 (SOLAR<sub>NSCLC</sub>)] | ||
|2016-2017 | |2016-2017 | ||
− | | style="background-color:#1a9851" |Phase | + | | style="background-color:#1a9851" |Phase 3 (C) |
|Naquotinib | |Naquotinib | ||
| style="background-color:#ffffbf" |Did not meet primary endpoint of PFS | | style="background-color:#ffffbf" |Did not meet primary endpoint of PFS | ||
Line 846: | Line 846: | ||
|[https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(19)30634-5/fulltext Nakagawa et al. 2019 (RELAY)] | |[https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(19)30634-5/fulltext Nakagawa et al. 2019 (RELAY)] | ||
|2016-2018 | |2016-2018 | ||
− | | style="background-color:#1a9851" |Phase | + | | style="background-color:#1a9851" |Phase 3 (C) |
|[[#Erlotinib_.26_Ramucirumab|Erlotinib & Ramucirumab]] | |[[#Erlotinib_.26_Ramucirumab|Erlotinib & Ramucirumab]] | ||
| style="background-color:#d73027" |Inferior PFS | | style="background-color:#d73027" |Inferior PFS | ||
Line 914: | Line 914: | ||
|[https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(19)30035-X/fulltext Saito et al. 2019 (NEJ026)] | |[https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(19)30035-X/fulltext Saito et al. 2019 (NEJ026)] | ||
|2015-2016 | |2015-2016 | ||
− | | style="background-color:#1a9851" |Phase | + | | style="background-color:#1a9851" |Phase 3 (E-esc) |
|[[#Erlotinib_monotherapy|Erlotinib]] | |[[#Erlotinib_monotherapy|Erlotinib]] | ||
| style="background-color:#91cf60" |Seems to have superior PFS<br>Median PFS: 16.9 vs 13.3 mo<br>(HR 0.61, 95% CI 0.42-0.88) | | style="background-color:#91cf60" |Seems to have superior PFS<br>Median PFS: 16.9 vs 13.3 mo<br>(HR 0.61, 95% CI 0.42-0.88) | ||
Line 950: | Line 950: | ||
|[https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(19)30634-5/fulltext Nakagawa et al. 2019 (RELAY)] | |[https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(19)30634-5/fulltext Nakagawa et al. 2019 (RELAY)] | ||
|2016-2018 | |2016-2018 | ||
− | | style="background-color:#1a9851" |Phase | + | | style="background-color:#1a9851" |Phase 3 (E-RT-esc) |
|[[#Erlotinib_monotherapy|Erlotinib]] | |[[#Erlotinib_monotherapy|Erlotinib]] | ||
| style="background-color:#1a9850" |Superior PFS <br>Median PFS: 19.4 mo vs 12.4 mo <br>(HR 0.59, 95% CI 0.46-0.76) | | style="background-color:#1a9850" |Superior PFS <br>Median PFS: 19.4 mo vs 12.4 mo <br>(HR 0.59, 95% CI 0.46-0.76) | ||
Line 983: | Line 983: | ||
|[https://doi.org/10.1200/JCO.19.01154 Noronha et al. 2019] | |[https://doi.org/10.1200/JCO.19.01154 Noronha et al. 2019] | ||
|2016-2018 | |2016-2018 | ||
− | | style="background-color:#1a9851" |Phase | + | | style="background-color:#1a9851" |Phase 3 (E-esc) |
|[[#Gefitinib_monotherapy_2|Gefitinib]] | |[[#Gefitinib_monotherapy_2|Gefitinib]] | ||
| style="background-color:#1a9850" |Superior OS | | style="background-color:#1a9850" |Superior OS | ||
Line 1,012: | Line 1,012: | ||
|[https://doi.org/10.1200/JCO.19.01488 Hosomi et al. 2019 (NEJ009)] | |[https://doi.org/10.1200/JCO.19.01488 Hosomi et al. 2019 (NEJ009)] | ||
|2011-2015 | |2011-2015 | ||
− | | style="background-color:#1a9851" |Phase | + | | style="background-color:#1a9851" |Phase 3 (E-esc) |
|[[#Gefitinib_monotherapy_2|Gefitinib]] | |[[#Gefitinib_monotherapy_2|Gefitinib]] | ||
| style="background-color:#91cf60" |Seems to have superior OS | | style="background-color:#91cf60" |Seems to have superior OS | ||
Line 1,055: | Line 1,055: | ||
|[https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(09)70364-X/fulltext Mitsudomi et al. 2009 (WJTOG3405)] | |[https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(09)70364-X/fulltext Mitsudomi et al. 2009 (WJTOG3405)] | ||
|2006-2009 | |2006-2009 | ||
− | | style="background-color:#1a9851" |Phase | + | | style="background-color:#1a9851" |Phase 3 (E-switch-ooc) |
|[[#Cisplatin_.26_Docetaxel_.28DC.29|Cisplatin & Docetaxel]] | |[[#Cisplatin_.26_Docetaxel_.28DC.29|Cisplatin & Docetaxel]] | ||
| style="background-color:#1a9850" |Superior PFS | | style="background-color:#1a9850" |Superior PFS | ||
Line 1,061: | Line 1,061: | ||
|[https://www.nejm.org/doi/full/10.1056/NEJMoa0909530 Maemondo et al. 2010 (NEJ002)] | |[https://www.nejm.org/doi/full/10.1056/NEJMoa0909530 Maemondo et al. 2010 (NEJ002)] | ||
|2006-2009 | |2006-2009 | ||
− | | style="background-color:#1a9851" |Phase | + | | style="background-color:#1a9851" |Phase 3 (E-switch-ooc) |
|[[#Carboplatin_.26_Paclitaxel_.28CP.29|Carboplatin & Paclitaxel]] | |[[#Carboplatin_.26_Paclitaxel_.28CP.29|Carboplatin & Paclitaxel]] | ||
| style="background-color:#1a9850" |Superior PFS<br>Median PFS 10.8 vs 5.4 mo<br>(HR 0.30, 95% CI 0.22-0.41) | | style="background-color:#1a9850" |Superior PFS<br>Median PFS 10.8 vs 5.4 mo<br>(HR 0.30, 95% CI 0.22-0.41) | ||
Line 1,067: | Line 1,067: | ||
|[https://doi.org/10.1200/jco.2015.63.4154 Urata et al. 2016 (WJOG 5108L)] | |[https://doi.org/10.1200/jco.2015.63.4154 Urata et al. 2016 (WJOG 5108L)] | ||
|2009-2012 | |2009-2012 | ||
− | | style="background-color:#1a9851" |Phase | + | | style="background-color:#1a9851" |Phase 3 (C) |
|[[#Erlotinib_monotherapy|Erlotinib]] | |[[#Erlotinib_monotherapy|Erlotinib]] | ||
| style="background-color:#ffffbf" |Inconclusive whether non-inferior PFS | | style="background-color:#ffffbf" |Inconclusive whether non-inferior PFS | ||
Line 1,073: | Line 1,073: | ||
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5344291/ Yang et al. 2017 (CTONG 0901)] | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5344291/ Yang et al. 2017 (CTONG 0901)] | ||
|2009-2014 | |2009-2014 | ||
− | | style="background-color:#1a9851" |Phase | + | | style="background-color:#1a9851" |Phase 3 (C) |
|[[#Erlotinib_monotherapy|Erlotinib]] | |[[#Erlotinib_monotherapy|Erlotinib]] | ||
| style="background-color:#ffffbf" |Did not meet primary endpoint of PFS | | style="background-color:#ffffbf" |Did not meet primary endpoint of PFS | ||
Line 1,091: | Line 1,091: | ||
|[https://doi.org/10.1200/JCO.19.01488 Hosomi et al. 2019 (NEJ009)] | |[https://doi.org/10.1200/JCO.19.01488 Hosomi et al. 2019 (NEJ009)] | ||
|2011-2015 | |2011-2015 | ||
− | | style="background-color:#1a9851" |Phase | + | | style="background-color:#1a9851" |Phase 3 (C) |
|[[#GCP|GCP]] | |[[#GCP|GCP]] | ||
| style="background-color:#fc8d59" |Seems to have inferior OS | | style="background-color:#fc8d59" |Seems to have inferior OS | ||
Line 1,103: | Line 1,103: | ||
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5519810/ Patil et al. 2017] | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5519810/ Patil et al. 2017] | ||
|2012-2016 | |2012-2016 | ||
− | | style="background-color:#1a9851" |Phase | + | | style="background-color:#1a9851" |Phase 3 (E-switch-ooc) |
|[[#Carboplatin_.26_Pemetrexed|Carboplatin & Pemetrexed]], then [[#Pemetrexed_monotherapy_2|Pem maint.]] | |[[#Carboplatin_.26_Pemetrexed|Carboplatin & Pemetrexed]], then [[#Pemetrexed_monotherapy_2|Pem maint.]] | ||
| style="background-color:#1a9850" |Superior PFS | | style="background-color:#1a9850" |Superior PFS | ||
Line 1,109: | Line 1,109: | ||
|[https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(17)30608-3/fulltext Wu et al. 2017 (ARCHER 1050)] | |[https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(17)30608-3/fulltext Wu et al. 2017 (ARCHER 1050)] | ||
|2013-2015 | |2013-2015 | ||
− | | style="background-color:#1a9851" |Phase | + | | style="background-color:#1a9851" |Phase 3 (C) |
|[[#Dacomitinib_monotherapy|Dacomitinib]] | |[[#Dacomitinib_monotherapy|Dacomitinib]] | ||
| style="background-color:#fc8d59" |Seems to have inferior OS<sup>1</sup> | | style="background-color:#fc8d59" |Seems to have inferior OS<sup>1</sup> | ||
Line 1,115: | Line 1,115: | ||
|[https://www.nejm.org/doi/full/10.1056/NEJMoa1713137 Soria et al. 2017 (FLAURA)] | |[https://www.nejm.org/doi/full/10.1056/NEJMoa1713137 Soria et al. 2017 (FLAURA)] | ||
|2014-2016 | |2014-2016 | ||
− | | style="background-color:#1a9851" |Phase | + | | style="background-color:#1a9851" |Phase 3 (C) |
|[[#Osimertinib_monotherapy_2|Osimertinib]] | |[[#Osimertinib_monotherapy_2|Osimertinib]] | ||
| style="background-color:#fc8d59" |Seems to have inferior OS<sup>2</sup> | | style="background-color:#fc8d59" |Seems to have inferior OS<sup>2</sup> | ||
Line 1,121: | Line 1,121: | ||
|[https://doi.org/10.1200/JCO.19.01154 Noronha et al. 2019] | |[https://doi.org/10.1200/JCO.19.01154 Noronha et al. 2019] | ||
|2016-2018 | |2016-2018 | ||
− | | style="background-color:#1a9851" |Phase | + | | style="background-color:#1a9851" |Phase 3 (C) |
|[[#GCP|GCP]] | |[[#GCP|GCP]] | ||
| style="background-color:#d73027" |Inferior OS | | style="background-color:#d73027" |Inferior OS | ||
Line 1,207: | Line 1,207: | ||
|[https://doi.org/10.1093/annonc/mdx359 Shi et al. 2017 (CONVINCE)] | |[https://doi.org/10.1093/annonc/mdx359 Shi et al. 2017 (CONVINCE)] | ||
|2013-2014 | |2013-2014 | ||
− | | style="background-color:#1a9851" |Phase | + | | style="background-color:#1a9851" |Phase 3 (E-switch-ooc) |
|[[#Cisplatin_.26_Pemetrexed|Cisplatin & Pemetrexed]] x 4, then [[#Pemetrexed_monotherapy_2|Pemetrexed maintenance]] | |[[#Cisplatin_.26_Pemetrexed|Cisplatin & Pemetrexed]] x 4, then [[#Pemetrexed_monotherapy_2|Pemetrexed maintenance]] | ||
| style="background-color:#1a9850" |Superior PFS | | style="background-color:#1a9850" |Superior PFS | ||
Line 1,244: | Line 1,244: | ||
|[https://www.nejm.org/doi/full/10.1056/NEJMoa1713137 Soria et al. 2017 (FLAURA)] | |[https://www.nejm.org/doi/full/10.1056/NEJMoa1713137 Soria et al. 2017 (FLAURA)] | ||
|2014-2016 | |2014-2016 | ||
− | | style="background-color:#1a9851" |Phase | + | | style="background-color:#1a9851" |Phase 3 (E-RT-switch-ic) |
|1. [[#Erlotinib_monotherapy|Erlotinib]]<br> 2. [[#Gefitinib_monotherapy|Gefitinib]] | |1. [[#Erlotinib_monotherapy|Erlotinib]]<br> 2. [[#Gefitinib_monotherapy|Gefitinib]] | ||
| style="background-color:#91cf60" |Seems to have superior OS<sup>1</sup><br>Median OS: 38.6 vs 31.8 mo<br>(HR 0.80, 95% CI 0.64-1.00) | | style="background-color:#91cf60" |Seems to have superior OS<sup>1</sup><br>Median OS: 38.6 vs 31.8 mo<br>(HR 0.80, 95% CI 0.64-1.00) | ||
Line 1,363: | Line 1,363: | ||
|[https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(15)00121-7/fulltext Soria et al. 2015 (IMPRESS)] | |[https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(15)00121-7/fulltext Soria et al. 2015 (IMPRESS)] | ||
|2012-2013 | |2012-2013 | ||
− | | style="background-color:#1a9851" |Phase | + | | style="background-color:#1a9851" |Phase 3 (C) |
|Cisplatin, Pemetrexed, Gefitinib | |Cisplatin, Pemetrexed, Gefitinib | ||
| style="background-color:#ffffbf" |Did not meet primary endpoint of PFS | | style="background-color:#ffffbf" |Did not meet primary endpoint of PFS | ||
Line 1,404: | Line 1,404: | ||
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6762027/ Mok et al. 2016 (AURA3)] | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6762027/ Mok et al. 2016 (AURA3)] | ||
|2014-2015 | |2014-2015 | ||
− | | style="background-color:#1a9851" |Phase | + | | style="background-color:#1a9851" |Phase 3 (C) |
|[[#Osimertinib_monotherapy_2|Osimertinib]] | |[[#Osimertinib_monotherapy_2|Osimertinib]] | ||
| style="background-color:#d73027" |Inferior PFS | | style="background-color:#d73027" |Inferior PFS | ||
Line 1,448: | Line 1,448: | ||
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6762027/ Mok et al. 2016 (AURA3)] | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6762027/ Mok et al. 2016 (AURA3)] | ||
|2014-2015 | |2014-2015 | ||
− | | style="background-color:#1a9851" |Phase | + | | style="background-color:#1a9851" |Phase 3 (C) |
|[[#Osimertinib_monotherapy_2|Osimertinib]] | |[[#Osimertinib_monotherapy_2|Osimertinib]] | ||
| style="background-color:#d73027" |Inferior PFS | | style="background-color:#d73027" |Inferior PFS | ||
Line 1,492: | Line 1,492: | ||
|[https://www.lungcancerjournal.info/article/S0169-5002(18)30340-4/fulltext Nie et al. 2018 (QingdaoCH20161101)] | |[https://www.lungcancerjournal.info/article/S0169-5002(18)30340-4/fulltext Nie et al. 2018 (QingdaoCH20161101)] | ||
|2015-2016 | |2015-2016 | ||
− | | style="background-color:#1a9851" |Phase | + | | style="background-color:#1a9851" |Phase 3 (C) |
|[[#Osimertinib_monotherapy_3|Osimertinib]] | |[[#Osimertinib_monotherapy_3|Osimertinib]] | ||
| style="background-color:#d73027" |Inferior PFS | | style="background-color:#d73027" |Inferior PFS | ||
Line 1,542: | Line 1,542: | ||
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6762027/ Mok et al. 2016 (AURA3)] | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6762027/ Mok et al. 2016 (AURA3)] | ||
|2014-2015 | |2014-2015 | ||
− | | style="background-color:#1a9851" |Phase | + | | style="background-color:#1a9851" |Phase 3 (E-RT-switch-ooc) |
|1. [[#Carboplatin_.26_Pemetrexed|Carboplatin & Pemetrexed]]<br> 2. [[#Cisplatin_.26_Pemetrexed|Cisplatin & Pemetrexed]] | |1. [[#Carboplatin_.26_Pemetrexed|Carboplatin & Pemetrexed]]<br> 2. [[#Cisplatin_.26_Pemetrexed|Cisplatin & Pemetrexed]] | ||
| style="background-color:#1a9850" |Superior PFS<br>Median PFS: 10.1 vs 4.4 mo<br>(HR 0.30, 95% CI 0.23-0.41) | | style="background-color:#1a9850" |Superior PFS<br>Median PFS: 10.1 vs 4.4 mo<br>(HR 0.30, 95% CI 0.23-0.41) | ||
Line 1,548: | Line 1,548: | ||
|[https://www.lungcancerjournal.info/article/S0169-5002(18)30340-4/fulltext Nie et al. 2018 (QingdaoCH20161101)] | |[https://www.lungcancerjournal.info/article/S0169-5002(18)30340-4/fulltext Nie et al. 2018 (QingdaoCH20161101)] | ||
|2015-2016 | |2015-2016 | ||
− | | style="background-color:#1a9851" |Phase | + | | style="background-color:#1a9851" |Phase 3 (E-switch-ooc) |
|[[#Docetaxel_.26_Bevacizumab|Docetaxel & Bevacizumab]] | |[[#Docetaxel_.26_Bevacizumab|Docetaxel & Bevacizumab]] | ||
| style="background-color:#1a9850" |Superior PFS | | style="background-color:#1a9850" |Superior PFS | ||
Line 1,587: | Line 1,587: | ||
|[https://doi.org/10.1200/jco.2012.44.2806 Sequist et al. 2013 (LUX-Lung 3)] | |[https://doi.org/10.1200/jco.2012.44.2806 Sequist et al. 2013 (LUX-Lung 3)] | ||
|2009-2011 | |2009-2011 | ||
− | | style="background-color:#1a9851" |Phase | + | | style="background-color:#1a9851" |Phase 3 (E-switch-ooc) |
|[[Non-small_cell_lung_cancer#Cisplatin_.26_Pemetrexed_2|Cisplatin & Pemetrexed]] | |[[Non-small_cell_lung_cancer#Cisplatin_.26_Pemetrexed_2|Cisplatin & Pemetrexed]] | ||
| style="background-color:#91cf60" |Seems to have superior PFS<sup>1</sup> | | style="background-color:#91cf60" |Seems to have superior PFS<sup>1</sup> | ||
Line 1,593: | Line 1,593: | ||
|[https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(13)70604-1/fulltext Wu et al. 2014 (LUX-Lung 6)] | |[https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(13)70604-1/fulltext Wu et al. 2014 (LUX-Lung 6)] | ||
|2010-2011 | |2010-2011 | ||
− | | style="background-color:#1a9851" |Phase | + | | style="background-color:#1a9851" |Phase 3 (E-switch-ooc) |
|[[Non-small cell lung cancer#Cisplatin_.26_Gemcitabine_.28GC.29_2|Cisplatin & Gemcitabine]] | |[[Non-small cell lung cancer#Cisplatin_.26_Gemcitabine_.28GC.29_2|Cisplatin & Gemcitabine]] | ||
| style="background-color:#91cf60" |Seems to have superior PFS<sup>1</sup> | | style="background-color:#91cf60" |Seems to have superior PFS<sup>1</sup> | ||
Line 1,638: | Line 1,638: | ||
|[https://www.thelancet.com/journals/lanres/article/PIIS2213-2600(17)30262-X/fulltext Yang et al. 2017 (BRAIN)] | |[https://www.thelancet.com/journals/lanres/article/PIIS2213-2600(17)30262-X/fulltext Yang et al. 2017 (BRAIN)] | ||
|2012-2015 | |2012-2015 | ||
− | | style="background-color:#1a9851" |Phase | + | | style="background-color:#1a9851" |Phase 3 (E-switch-ooc) |
|WB-XRT | |WB-XRT | ||
| style="background-color:#91cf60" |Seems to have superior intracranial PFS | | style="background-color:#91cf60" |Seems to have superior intracranial PFS | ||
Line 1,685: | Line 1,685: | ||
|[https://www.nejm.org/doi/full/10.1056/NEJMoa1612674 Mok et al. 2016 (AURA3)] | |[https://www.nejm.org/doi/full/10.1056/NEJMoa1612674 Mok et al. 2016 (AURA3)] | ||
|2014-2015 | |2014-2015 | ||
− | | style="background-color:#1a9851" |Phase | + | | style="background-color:#1a9851" |Phase 3 (E-switch-ooc) |
|1. [[Non-small cell lung cancer#Carboplatin_.26_Pemetrexed_2|Carboplatin & Pemetrexed]]<br> 2. [[Non-small cell lung cancer#Cisplatin_.26_Pemetrexed_3|Cisplatin & Pemetrexed]] | |1. [[Non-small cell lung cancer#Carboplatin_.26_Pemetrexed_2|Carboplatin & Pemetrexed]]<br> 2. [[Non-small cell lung cancer#Cisplatin_.26_Pemetrexed_3|Cisplatin & Pemetrexed]] | ||
| style="background-color:#91cf60" |Seems to have superior ORR<sup>1</sup> | | style="background-color:#91cf60" |Seems to have superior ORR<sup>1</sup> | ||
Line 1,691: | Line 1,691: | ||
|[https://www.nejm.org/doi/full/10.1056/NEJMoa1713137 Soria et al. 2017 (FLAURA)] | |[https://www.nejm.org/doi/full/10.1056/NEJMoa1713137 Soria et al. 2017 (FLAURA)] | ||
|2014-2016 | |2014-2016 | ||
− | | style="background-color:#1a9851" |Phase | + | | style="background-color:#1a9851" |Phase 3 (E-switch-ic) |
|1. [[Non-small cell lung cancer#Erlotinib_monotherapy|Erlotinib]]<br> 2. [[Non-small cell lung cancer#Gefitinib_monotherapy|Gefitinib]] | |1. [[Non-small cell lung cancer#Erlotinib_monotherapy|Erlotinib]]<br> 2. [[Non-small cell lung cancer#Gefitinib_monotherapy|Gefitinib]] | ||
| style="background-color:#91cf60" |Seems to have superior PFS<sup>2</sup> | | style="background-color:#91cf60" |Seems to have superior PFS<sup>2</sup> |
Revision as of 02:29, 16 December 2021
Section editor transclusions Note: these are regimens tested in biomarker-specific populations, please see the main NSCLC page for other regimens.
46 regimens on this page
63 variants on this page
|
Guidelines
IASLC
- 2016: The International Association for the Study of Lung Cancer consensus statement on optimizing management of EGFR mutation–positive non–small cell lung cancer: Status in 2016 PubMed
Adjuvant therapy
Cisplatin & Vinorelbine
back to top |
CVb: Cisplatin & Vinorelbine
Regimen
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Zhong et al. 2017 (ADJUVANT/CTONG1104) | 2011-2014 | Phase 3 (C) | Gefinitib | Inferior DFS |
Biomarker Eligibility Criteria
- Biomarker: EGFR exon 19 deletion and exon 21 L858R activating mutations
Preceding treatment
- Complete surgical resection, within 6 to 12 weeks
Chemotherapy
- Cisplatin (Platinol) 75 mg/m2 IV once on day 1
- Vinorelbine (Navelbine) 30 mg/m2 IV once per day on days 1 & 8
21-day cycle for 4 cycles
References
- ADJUVANT/CTONG1104: Zhong WZ, Wang Q, Mao WM, Xu ST, Wu L, Shen Y, Liu YY, Chen C, Cheng Y, Xu L, Wang J, Fei K, Li XF, Li J, Huang C, Liu ZD, Xu S, Chen KN, Xu SD, Liu LX, Yu P, Wang BH, Ma HT, Yan HH, Yang XN, Zhou Q, Wu YL; ADJUVANT investigators. Gefitinib versus vinorelbine plus cisplatin as adjuvant treatment for stage II-IIIA (N1-N2) EGFR-mutant NSCLC (ADJUVANT/CTONG1104): a randomised, open-label, phase 3 study. Lancet Oncol. 2018 Jan;19(1):139-148. Epub 2017 Nov 21. link to original article contains protocol PubMed NCT01405079
- Update: Zhong WZ, Wang Q, Mao WM, Xu ST, Wu L, Wei YC, Liu YY, Chen C, Cheng Y, Yin R, Yang F, Ren SX, Li XF, Li J, Huang C, Liu ZD, Xu S, Chen KN, Xu SD, Liu LX, Yu P, Wang BH, Ma HT, Yang JJ, Yan HH, Yang XN, Liu SY, Zhou Q, Wu YL. Gefitinib Versus Vinorelbine Plus Cisplatin as Adjuvant Treatment for Stage II-IIIA (N1-N2) EGFR-Mutant NSCLC: Final Overall Survival Analysis of CTONG1104 Phase III Trial. J Clin Oncol. 2021 Mar 1;39(7):713-722. Epub 2020 Dec 17. link to original article PubMed
Gefitinib monotherapy
back to top |
Regimen
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Zhong et al. 2017 (ADJUVANT/CTONG1104) | 2011-2014 | Phase 3 (E-switch-ooc) | Cisplatin & Vinorelbine | Superior DFS Median DFS: 28.7 vs 18 mo (HR 0.60, 95% CI 0.42-0.87) |
Biomarker Eligibility Criteria
- Biomarker: EGFR exon 19 deletion and exon 21 L858R activating mutations
Preceding treatment
Targeted therapy
- Gefitinib (Iressa) 250 mg PO once per day
24-month course
References
- ADJUVANT/CTONG1104: Zhong WZ, Wang Q, Mao WM, Xu ST, Wu L, Shen Y, Liu YY, Chen C, Cheng Y, Xu L, Wang J, Fei K, Li XF, Li J, Huang C, Liu ZD, Xu S, Chen KN, Xu SD, Liu LX, Yu P, Wang BH, Ma HT, Yan HH, Yang XN, Zhou Q, Wu YL; ADJUVANT investigators. Gefitinib versus vinorelbine plus cisplatin as adjuvant treatment for stage II-IIIA (N1-N2) EGFR-mutant NSCLC (ADJUVANT/CTONG1104): a randomised, open-label, phase 3 study. Lancet Oncol. 2018 Jan;19(1):139-148. Epub 2017 Nov 21. link to original article contains protocol PubMed NCT01405079
- Update: Zhong WZ, Wang Q, Mao WM, Xu ST, Wu L, Wei YC, Liu YY, Chen C, Cheng Y, Yin R, Yang F, Ren SX, Li XF, Li J, Huang C, Liu ZD, Xu S, Chen KN, Xu SD, Liu LX, Yu P, Wang BH, Ma HT, Yang JJ, Yan HH, Yang XN, Liu SY, Zhou Q, Wu YL. Gefitinib Versus Vinorelbine Plus Cisplatin as Adjuvant Treatment for Stage II-IIIA (N1-N2) EGFR-Mutant NSCLC: Final Overall Survival Analysis of CTONG1104 Phase III Trial. J Clin Oncol. 2021 Mar 1;39(7):713-722. Epub 2020 Dec 17. link to original article PubMed
Icotinib monotherapy
back to top |
Regimen
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
He et al. 2021 (EVIDENCE) | 2015-2019 | Phase 3 (E-switch-ooc) | 1. Cisplatin & Pemetrexed 2. Cisplatinb & Vinorelbine |
Superior DFS Median DFS: 47 vs 22.1 mo (HR 0.36, 95% CI 0.24-0.55) |
Note: this drug is only approved in China; eligible patients had stage IIIB/IV lung adenocarcinoma.
Biomarker eligibility criteria
- EGFR exon 19 or 21 mutations
Preceding treatment
- Complete resection, within 8 weeks
Targeted therapy
- Icotinib (Conmana) 125 mg PO three times per day
2-year course
References
- EVIDENCE: He J, Su C, Liang W, Xu S, Wu L, Fu X, Zhang X, Ge D, Chen Q, Mao W, Xu L, Chen C, Hu B, Shao G, Hu J, Zhao J, Liu X, Liu Z, Wang Z, Xiao Z, Gong T, Lin W, Li X, Ye F, Liu Y, Ma H, Huang Y, Zhou J, Wang Z, Fu J, Ding L, Mao L, Zhou C. Icotinib versus chemotherapy as adjuvant treatment for stage II-IIIA EGFR-mutant non-small-cell lung cancer (EVIDENCE): a randomised, open-label, phase 3 trial. Lancet Respir Med. 2021 Sep;9(9):1021-1029. Epub 2021 Jul 21. link to original article contains protocol PubMed NCT02448797
Osimertinib monotherapy
back to top |
Regimen
FDA-recommended dose |
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Wu et al. 2020 (ADAURA) | 2015-2019 | Phase 3 (E-RT-esc) | Placebo | Superior DFS DFS24: 90% vs 44% (HR 0.17, 99.06% CI 0.11-0.26) |
Biomarker eligibility criteria
- EGFR exon 19 deletion or p.L858R mutation, alone or in combination with other EGFR mutations
Preceding treatment
Targeted therapy
- Osimertinib (Tagrisso) 80 mg PO once per day
3-year course
References
- ADAURA: Wu YL, Tsuboi M, He J, John T, Grohe C, Majem M, Goldman JW, Laktionov K, Kim SW, Kato T, Vu HV, Lu S, Lee KY, Akewanlop C, Yu CJ, de Marinis F, Bonanno L, Domine M, Shepherd FA, Zeng L, Hodge R, Atasoy A, Rukazenkov Y, Herbst RS; ADAURA Investigators. Osimertinib in Resected EGFR-Mutated Non-Small-Cell Lung Cancer. N Engl J Med. 2020 Oct 29;383(18):1711-1723. Epub 2020 Sep 19. link to original article contains verified protocol PubMed NCT02511106
Advanced or metastatic disease, platinum-exposed
Amivantamab monotherapy
back to top |
Regimen variant #1
FDA-recommended dose |
Study | Years of enrollment | Evidence |
---|---|---|
Awaiting publication (CHRYSALIS) | 2016-NR | Phase 1 (RT) |
Note: this study is unpublished; dosing details are from the FDA announcement. This is the recommended dose for patients weighing less than 80 kg.
Biomarker eligibility criteria
- EGFR exon 20 insertion
Targeted therapy
- Amivantamab (Rybrevant) 1050 mg IV once on day 1
7-day cycle for 4 cycles, then 14-day cycles
Regimen variant #2
FDA-recommended dose |
Study | Years of enrollment | Evidence |
---|---|---|
Awaiting publication (CHRYSALIS) | 2016-NR | Phase 1 (RT) |
Note: this study is unpublished; dosing details are from the FDA announcement. This is the recommended dose for patients weighing 80 kg or more.
Biomarker eligibility criteria
- EGFR exon 20 insertion
Targeted therapy
- Amivantamab (Rybrevant) 1400 mg IV once on day 1
7-day cycle for 4 cycles, then 14-day cycles
References
- CHRYSALIS: NCT02609776
Mobocertinib monotherapy
back to top |
Regimen
FDA-recommended dose |
Study | Years of enrollment | Evidence |
---|---|---|
Riely et al. 2021 (AP32788-15-101) | 2016-ongoing | Phase I/II (RT) |
Note: this was the dose used in the phase II portion.
Biomarker eligibility criteria
- EGFR exon 20 insertion mutations
Targeted therapy
- Mobocertinib (Exkivity) 160 mg PO once per day
28-day cycles
References
- AP32788-15-101: Riely GJ, Neal JW, Camidge DR, Spira AI, Piotrowska Z, Costa DB, Tsao AS, Patel JD, Gadgeel SM, Bazhenova L, Zhu VW, West HL, Mekhail T, Gentzler RD, Nguyen D, Vincent S, Zhang S, Lin J, Bunn V, Jin S, Li S, Jänne PA. Activity and Safety of Mobocertinib (TAK-788) in Previously Treated Non-Small Cell Lung Cancer with EGFR Exon 20 Insertion Mutations from a Phase I/II Trial. Cancer Discov. 2021 Jul;11(7):1688-1699. Epub 2021 Feb 25. link to original article link to PMC article contains verified protocol PubMed NCT02716116
Advanced or metastatic disease, EGFR inhibitor-naive
Afatinib monotherapy
back to top |
Regimen variant #1, 30 mg/day
FDA-recommended dose |
This is the FDA-recommended dose for patients with "severe renal impairment".
Targeted therapy
- Afatinib (Gilotrif) 30 mg PO once per day
Continued indefinitely
Regimen variant #2, 40 mg/day
FDA-recommended dose |
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Yang et al. 2012 (LUX-Lung 2) | 2007-2009 | Phase II (RT) | ORR: 61% | |
Sequist et al. 2013 (LUX-Lung 3) | 2009-2011 | Phase 3 (E-RT-switch-ooc) | Cisplatin & Pemetrexed | Superior PFS |
Wu et al. 2014 (LUX-Lung 6) | 2010-2011 | Phase 3 (E-RT-switch-ooc) | Cisplatin & Gemcitabine | Superior PFS |
Park et al. 2016 (LUX-Lung 7) | 2011-2013 | Randomized Phase II (E-switch-ic) | Gefitinib | Seems to have superior PFS |
Biomarker Eligibility Criteria
- Biomarker:
- activating EGFR mutations within exons 18–21 (LUX LUNG-2)
- activating EGFR mutation with 19 deletions in exon 19, L858R, 3 insertions in exon 20, L861Q, G719S, G719A, G719C, T790M and S768I (LUX-LUNG 3, LUX-LUNG 6)
- activating EGFR mutation with exon 19 deletion and/or L858R (LUX-LUNG 7)
Targeted therapy
- Afatinib (Gilotrif) 40 mg PO once per day, given 1 hour before eating food (LUX-Lung 2: "no food intake immediately before or after afatinib")
- In LUX-Lung 3, patients could be increased to 50 mg PO once per day if they did not experience any grade 2 or higher rash, diarrhea, mucositis, or other drug-related adverse event.
Continued indefinitely
References
- LUX-Lung 2: Yang JC, Shih JY, Su WC, Hsia TC, Tsai CM, Ou SH, Yu CJ, Chang GC, Ho CL, Sequist LV, Dudek AZ, Shahidi M, Cong XJ, Lorence RM, Yang PC, Miller VA. Afatinib for patients with lung adenocarcinoma and epidermal growth factor receptor mutations (LUX-Lung 2): a phase 2 trial. Lancet Oncol. 2012 May;13(5):539-48. Epub 2012 Mar 26. link to original article contains verified protocol PubMed NCT00525148
- Pooled analysis: Yang JC, Sequist LV, Geater SL, Tsai CM, Mok TS, Schuler M, Yamamoto N, Yu CJ, Ou SH, Zhou C, Massey D, Zazulina V, Wu YL. Clinical activity of afatinib in patients with advanced non-small-cell lung cancer harbouring uncommon EGFR mutations: a combined post-hoc analysis of LUX-Lung 2, LUX-Lung 3, and LUX-Lung 6. Lancet Oncol. 2015 Jul;16(7):830-8. Epub 2015 Jun 4. link to original article PubMed
- LUX-Lung 3: Sequist LV, Yang JC, Yamamoto N, O'Byrne K, Hirsh V, Mok T, Geater SL, Orlov S, Tsai CM, Boyer M, Su WC, Bennouna J, Kato T, Gorbunova V, Lee KH, Shah R, Massey D, Zazulina V, Shahidi M, Schuler M. Phase III study of afatinib or cisplatin plus pemetrexed in patients with metastatic lung adenocarcinoma with EGFR mutations. J Clin Oncol. 2013 Sep 20;31(27):3327-34. Epub 2013 Jul 1. link to original article contains verified protocol PubMed NCT00949650
- HRQoL analysis: Yang JC, Hirsh V, Schuler M, Yamamoto N, O'Byrne KJ, Mok TS, Zazulina V, Shahidi M, Lungershausen J, Massey D, Palmer M, Sequist LV. Symptom control and quality of life in LUX-Lung 3: a phase III study of afatinib or cisplatin/pemetrexed in patients with advanced lung adenocarcinoma with EGFR mutations. J Clin Oncol. 2013 Sep 20;31(27):3342-50. Epub 2013 Jul 1. link to original article contains verified protocol PubMed
- Pooled update: Yang JC, Wu YL, Schuler M, Sebastian M, Popat S, Yamamoto N, Zhou C, Hu CP, O'Byrne K, Feng J, Lu S, Huang Y, Geater SL, Lee KY, Tsai CM, Gorbunova V, Hirsh V, Bennouna J, Orlov S, Mok T, Boyer M, Su WC, Lee KH, Kato T, Massey D, Shahidi M, Zazulina V, Sequist LV. Afatinib versus cisplatin-based chemotherapy for EGFR mutation-positive lung adenocarcinoma (LUX-Lung 3 and LUX-Lung 6): analysis of overall survival data from two randomised, phase 3 trials. Lancet Oncol. 2015 Feb;16(2):141-51. link to original article PubMed
- Pooled analysis: Yang JC, Sequist LV, Geater SL, Tsai CM, Mok TS, Schuler M, Yamamoto N, Yu CJ, Ou SH, Zhou C, Massey D, Zazulina V, Wu YL. Clinical activity of afatinib in patients with advanced non-small-cell lung cancer harbouring uncommon EGFR mutations: a combined post-hoc analysis of LUX-Lung 2, LUX-Lung 3, and LUX-Lung 6. Lancet Oncol. 2015 Jul;16(7):830-8. Epub 2015 Jun 4. link to original article PubMed
- Subgroup analysis: Schuler M, Wu YL, Hirsh V, O'Byrne K, Yamamoto N, Mok T, Popat S, Sequist LV, Massey D, Zazulina V, Yang JC. First-line afatinib versus chemotherapy in patients with non-small cell lung cancer and common epidermal growth factor receptor gene mutations and brain metastases. J Thorac Oncol. 2016 Mar;11(3):380-90. link to original article PubMed
- LUX-Lung 6: Wu YL, Zhou C, Hu CP, Feng J, Lu S, Huang Y, Li W, Hou M, Shi JH, Lee KY, Xu CR, Massey D, Kim M, Shi Y, Geater SL. Afatinib versus cisplatin plus gemcitabine for first-line treatment of Asian patients with advanced non-small-cell lung cancer harbouring EGFR mutations (LUX-Lung 6): an open-label, randomised phase 3 trial. Lancet Oncol. 2014 Feb;15(2):213-22. link to original article contains verified protocol PubMed NCT01121393
- Pooled update: Yang JC, Wu YL, Schuler M, Sebastian M, Popat S, Yamamoto N, Zhou C, Hu CP, O'Byrne K, Feng J, Lu S, Huang Y, Geater SL, Lee KY, Tsai CM, Gorbunova V, Hirsh V, Bennouna J, Orlov S, Mok T, Boyer M, Su WC, Lee KH, Kato T, Massey D, Shahidi M, Zazulina V, Sequist LV. Afatinib versus cisplatin-based chemotherapy for EGFR mutation-positive lung adenocarcinoma (LUX-Lung 3 and LUX-Lung 6): analysis of overall survival data from two randomised, phase 3 trials. Lancet Oncol. 2015 Feb;16(2):141-51. link to original article PubMed
- Pooled analysis: Yang JC, Sequist LV, Geater SL, Tsai CM, Mok TS, Schuler M, Yamamoto N, Yu CJ, Ou SH, Zhou C, Massey D, Zazulina V, Wu YL. Clinical activity of afatinib in patients with advanced non-small-cell lung cancer harbouring uncommon EGFR mutations: a combined post-hoc analysis of LUX-Lung 2, LUX-Lung 3, and LUX-Lung 6. Lancet Oncol. 2015 Jul;16(7):830-8. Epub 2015 Jun 4. link to original article PubMed
- Subgroup analysis: Schuler M, Wu YL, Hirsh V, O'Byrne K, Yamamoto N, Mok T, Popat S, Sequist LV, Massey D, Zazulina V, Yang JC. First-line afatinib versus chemotherapy in patients with non-small cell lung cancer and common epidermal growth factor receptor gene mutations and brain metastases. J Thorac Oncol. 2016 Mar;11(3):380-90. link to original article PubMed
- LUX-Lung 7: Park K, Tan EH, O'Byrne K, Zhang L, Boyer M, Mok T, Hirsh V, Yang JC, Lee KH, Lu S, Shi Y, Kim SW, Laskin J, Kim DW, Arvis CD, Kölbeck K, Laurie SA, Tsai CM, Shahidi M, Kim M, Massey D, Zazulina V, Paz-Ares L. Afatinib versus gefitinib as first-line treatment of patients with EGFR mutation-positive non-small-cell lung cancer (LUX-Lung 7): a phase 2B, open-label, randomised controlled trial. Lancet Oncol. 2016 May;17(5):577-89. Epub 2016 Apr 12. link to original article contains protocol PubMed NCT01466660
Carboplatin & Docetaxel
back to top |
DCb: Docetaxel & Carboplatin
Regimen
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Rossell et al. 2012 (EURTAC) | 2007-2011 | Phase 3 (C) | Erlotinib | Inferior PFS |
Biomarker Eligibility Criteria
- Biomarker: EGFR activating mutation with exon 19 deletion or p.L858R mutation in exon 21
Chemotherapy
- Carboplatin (Paraplatin) AUC 6 IV once on day 1
- Docetaxel (Taxotere) 75 mg/m2 IV once on day 1
21-day cycles
References
- EURTAC: Rosell R, Carcereny E, Gervais R, Vergnenegre A, Massuti B, Felip E, Palmero R, Garcia-Gomez R, Pallares C, Sanchez JM, Porta R, Cobo M, Garrido P, Longo F, Moran T, Insa A, De Marinis F, Corre R, Bover I, Illiano A, Dansin E, de Castro J, Milella M, Reguart N, Altavilla G, Jimenez U, Provencio M, Moreno MA, Terrasa J, Muñoz-Langa J, Valdivia J, Isla D, Domine M, Molinier O, Mazieres J, Baize N, Garcia-Campelo R, Robinet G, Rodriguez-Abreu D, Lopez-Vivanco G, Gebbia V, Ferrera-Delgado L, Bombaron P, Bernabe R, Bearz A, Artal A, Cortesi E, Rolfo C, Sanchez-Ronco M, Drozdowskyj A, Queralt C, de Aguirre I, Ramirez JL, Sanchez JJ, Molina MA, Taron M, Paz-Ares L; Spanish Lung Cancer Group; Groupe Français de Pneumo-Cancérologie; Associazione Italiana Oncologia Toracica. Erlotinib versus standard chemotherapy as first-line treatment for European patients with advanced EGFR mutation-positive non-small-cell lung cancer (EURTAC): a multicentre, open-label, randomised phase 3 trial. Lancet Oncol. 2012 Mar;13(3):239-46. Epub 2012 Jan 26. link to original article contains protocol PubMed NCT00446225
Carboplatin & Gemcitabine (GCb)
back to top |
GC: Gemcitabine & Carboplatin
GCa: Gemcitabine & Carboplatin
GCb: Gemcitabine & Carboplatin
Regimen
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Rossell et al. 2012 (EURTAC) | 2007-2011 | Phase 3 (C) | Erlotinib | Inferior PFS |
Zhou et al. 2011 (CTONG-0802) | 2008-2009 | Phase 3 (C) | Erlotinib | Inferior PFS |
Biomarker Eligibility Criteria
- Biomarker: EGFR activating mutation with exon 19 deletion or p.L858R mutation in exon 21
Chemotherapy
- Carboplatin (Paraplatin) AUC 5 IV once on day 1
- Gemcitabine (Gemzar) 1000 mg/m2 IV once per day on days 1 & 8
21-day cycle for up to 4 cycles
References
- CTONG-0802: Zhou C, Wu YL, Chen G, Feng J, Liu XQ, Wang C, Zhang S, Wang J, Zhou S, Ren S, Lu S, Zhang L, Hu C, Hu C, Luo Y, Chen L, Ye M, Huang J, Zhi X, Zhang Y, Xiu Q, Ma J, Zhang L, You C. Erlotinib versus chemotherapy as first-line treatment for patients with advanced EGFR mutation-positive non-small-cell lung cancer (OPTIMAL, CTONG-0802): a multicentre, open-label, randomised, phase 3 study. Lancet Oncol. 2011 Aug;12(8):735-42. Epub 2011 Jul 23. link to original article PubMed NCT00874419
- Update: Zhou C, Wu YL, Chen G, Feng J, Liu XQ, Wang C, Zhang S, Wang J, Zhou S, Ren S, Lu S, Zhang L, Hu C, Hu C, Luo Y, Chen L, Ye M, Huang J, Zhi X, Zhang Y, Xiu Q, Ma J, Zhang L, You C. Final overall survival results from a randomised, phase III study of erlotinib versus chemotherapy as first-line treatment of EGFR mutation-positive advanced non-small-cell lung cancer (OPTIMAL, CTONG-0802). Ann Oncol. 2015 Sep;26(9):1877-83. Epub 2015 Jul 3. link to original article contains verified protocol PubMed
- EURTAC: Rosell R, Carcereny E, Gervais R, Vergnenegre A, Massuti B, Felip E, Palmero R, Garcia-Gomez R, Pallares C, Sanchez JM, Porta R, Cobo M, Garrido P, Longo F, Moran T, Insa A, De Marinis F, Corre R, Bover I, Illiano A, Dansin E, de Castro J, Milella M, Reguart N, Altavilla G, Jimenez U, Provencio M, Moreno MA, Terrasa J, Muñoz-Langa J, Valdivia J, Isla D, Domine M, Molinier O, Mazieres J, Baize N, Garcia-Campelo R, Robinet G, Rodriguez-Abreu D, Lopez-Vivanco G, Gebbia V, Ferrera-Delgado L, Bombaron P, Bernabe R, Bearz A, Artal A, Cortesi E, Rolfo C, Sanchez-Ronco M, Drozdowskyj A, Queralt C, de Aguirre I, Ramirez JL, Sanchez JJ, Molina MA, Taron M, Paz-Ares L; Spanish Lung Cancer Group; Groupe Français de Pneumo-Cancérologie; Associazione Italiana Oncologia Toracica. Erlotinib versus standard chemotherapy as first-line treatment for European patients with advanced EGFR mutation-positive non-small-cell lung cancer (EURTAC): a multicentre, open-label, randomised phase 3 trial. Lancet Oncol. 2012 Mar;13(3):239-46. Epub 2012 Jan 26. link to original article contains protocol PubMed NCT00446225
Carboplatin & Gemcitabine/Erlotinib
back to top |
Regimen
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Wu et al. 2013 (FASTACT-2) | 2009-2010 | Phase 3 (E-esc) | Carboplatin & Gemcitabine | Seems to have superior OS |
Note: this cohort was enriched for EGFR mutations and only those patients with an activating EGFR gene mutation were noted to have a treatment benefit in favor of the experimental arm.
Chemotherapy
- Carboplatin (Paraplatin) AUC 5 IV once on day 1
- Gemcitabine (Gemzar) 1250 mg/m2 IV once per day on days 1 & 8
Targeted therapy
- Erlotinib (Tarceva) 150 mg PO once per day on days 15 to 28
28-day cycle for 4 cycles
References
- FASTACT-2: Wu YL, Lee JS, Thongprasert S, Yu CJ, Zhang L, Ladrera G, Srimuninnimit V, Sriuranpong V, Sandoval-Tan J, Zhu Y, Liao M, Zhou C, Pan H, Lee V, Chen YM, Sun Y, Margono B, Fuerte F, Chang GC, Seetalarom K, Wang J, Cheng A, Syahruddin E, Qian X, Ho J, Kurnianda J, Liu HE, Jin K, Truman M, Bara I, Mok T. Intercalated combination of chemotherapy and erlotinib for patients with advanced stage non-small-cell lung cancer (FASTACT-2): a randomised, double-blind trial. Lancet Oncol. 2013 Jul;14(8):777-86. Epub 2013 Jun 17. link to original article contains protocol PubMed NCT00883779
Carboplatin & Paclitaxel (CP)
back to top |
CP: Carboplatin & Paclitaxel
PC: Paclitaxel & Carboplatin
TC: Taxol (Paclitaxel) & Carboplatin
Regimen
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Maemondo et al. 2010 (NEJ002) | 2006-2009 | Phase 3 (C) | Gefitinib | Inferior PFS |
Chemotherapy
- Carboplatin (Paraplatin) AUC 6 IV over 15 to 60 minutes once on day 1, given second
- Paclitaxel (Taxol) 200 mg/m2 IV over 3 hours once on day 1, given first
21-day cycle for at least 3 cycles
References
- NEJ002: Maemondo M, Inoue A, Kobayashi K, Sugawara S, Oizumi S, Isobe H, Gemma A, Harada M, Yoshizawa H, Kinoshita I, Fujita Y, Okinaga S, Hirano H, Yoshimori K, Harada T, Ogura T, Ando M, Miyazawa H, Tanaka T, Saijo Y, Hagiwara K, Morita S, Nukiwa T; North-East Japan Study Group. Gefitinib or chemotherapy for non-small-cell lung cancer with mutated EGFR. N Engl J Med. 2010 Jun 24;362(25):2380-8. link to original article contains verified protocol PubMed UMIN000000376
- HRQoL analysis: Oizumi S, Kobayashi K, Inoue A, Maemondo M, Sugawara S, Yoshizawa H, Isobe H, Harada M, Kinoshita I, Okinaga S, Kato T, Harada T, Gemma A, Saijo Y, Yokomizo Y, Morita S, Hagiwara K, Nukiwa T. Quality of life with gefitinib in patients with EGFR-mutated non-small cell lung cancer: quality of life analysis of North East Japan Study Group 002 Trial. Oncologist. 2012;17(6):863-70. Epub 2012 May 11. link to original article link to PMC article PubMed
- Update: Inoue A, Kobayashi K, Maemondo M, Sugawara S, Oizumi S, Isobe H, Gemma A, Harada M, Yoshizawa H, Kinoshita I, Fujita Y, Okinaga S, Hirano H, Yoshimori K, Harada T, Saijo Y, Hagiwara K, Morita S, Nukiwa T; North-East Japan Study Group. Updated overall survival results from a randomized phase III trial comparing gefitinib with carboplatin-paclitaxel for chemo-naïve non-small cell lung cancer with sensitive EGFR gene mutations (NEJ002). Ann Oncol. 2013 Jan;24(1):54-9. Epub 2012 Sep 11. link to original article PubMed
Cisplatin & Docetaxel (DC)
back to top |
DC: Docetaxel & Cisplatin
DP: Docetaxel & Platinol (Cisplatin)
Doc-Cis: Docetaxel & Cisplatin
Regimen variant #1, 75/75
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Rossell et al. 2012 (EURTAC) | 2007-2011 | Phase 3 (C) | Erlotinib | Inferior PFS |
Patients in EURTAC had EGFR exon 19 deletion or p.L858R mutation.
Chemotherapy
- Cisplatin (Platinol) 75 mg/m2 IV once on day 1
- Docetaxel (Taxotere) 75 mg/m2 IV once on day 1
21-day cycle for up to 4 cycles
Regimen variant #2, 80/60
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Mitsudomi et al. 2009 (WJTOG3405) | 2006-2009 | Phase 3 (C) | Gefitinib | Inferior PFS |
Patients in WJTOG3405 had EGFR exon 19 deletion or p.L858R mutation.
Chemotherapy
- Cisplatin (Platinol) 80 mg/m2 IV over 90 minutes once on day 1, given second
- Docetaxel (Taxotere) 60 mg/m2 IV over 60 minutes once on day 1, given first
21-day cycle for 3 to 6 cycles
References
- WJTOG3405: Mitsudomi T, Morita S, Yatabe Y, Negoro S, Okamoto I, Tsurutani J, Seto T, Satouchi M, Tada H, Hirashima T, Asami K, Katakami N, Takada M, Yoshioka H, Shibata K, Kudoh S, Shimizu E, Saito H, Toyooka S, Nakagawa K, Fukuoka M; West Japan Thoracic Oncology Group. Gefitinib versus cisplatin plus docetaxel in patients with non-small-cell lung cancer harbouring mutations of the epidermal growth factor receptor (WJTOG3405): an open label, randomised phase 3 trial. Lancet Oncol. 2010 Feb;11(2):121-8. Epub 2009 Dec 18. link to original article contains verified protocol PubMed UMIN000000539
- Update: Yoshioka H, Shimokawa M, Seto T, Morita S, Yatabe Y, Okamoto I, Tsurutani J, Satouchi M, Hirashima T, Atagi S, Shibata K, Saito H, Toyooka S, Yamamoto N, Nakagawa K, Mitsudomi T. Final overall survival results of WJTOG3405, a randomized phase III trial comparing gefitinib versus cisplatin with docetaxel as the first-line treatment for patients with stage IIIB/IV or postoperative recurrent EGFR mutation-positive non-small-cell lung cancer. Ann Oncol. 2019 Dec 1;30(12):1978-1984. link to original article PubMed
- EURTAC: Rosell R, Carcereny E, Gervais R, Vergnenegre A, Massuti B, Felip E, Palmero R, Garcia-Gomez R, Pallares C, Sanchez JM, Porta R, Cobo M, Garrido P, Longo F, Moran T, Insa A, De Marinis F, Corre R, Bover I, Illiano A, Dansin E, de Castro J, Milella M, Reguart N, Altavilla G, Jimenez U, Provencio M, Moreno MA, Terrasa J, Muñoz-Langa J, Valdivia J, Isla D, Domine M, Molinier O, Mazieres J, Baize N, Garcia-Campelo R, Robinet G, Rodriguez-Abreu D, Lopez-Vivanco G, Gebbia V, Ferrera-Delgado L, Bombaron P, Bernabe R, Bearz A, Artal A, Cortesi E, Rolfo C, Sanchez-Ronco M, Drozdowskyj A, Queralt C, de Aguirre I, Ramirez JL, Sanchez JJ, Molina MA, Taron M, Paz-Ares L; Spanish Lung Cancer Group; Groupe Français de Pneumo-Cancérologie; Associazione Italiana Oncologia Toracica. Erlotinib versus standard chemotherapy as first-line treatment for European patients with advanced EGFR mutation-positive non-small-cell lung cancer (EURTAC): a multicentre, open-label, randomised phase 3 trial. Lancet Oncol. 2012 Mar;13(3):239-46. Epub 2012 Jan 26. link to original article contains protocol PubMed NCT00446225
Cisplatin & Gemcitabine (GC)
back to top |
GC: Gemcitabine & Cisplatin
GP: Gemcitabine & Platinol (Cisplatin)
Regimen variant #1, 75/1000
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Wu et al. 2014 (LUX-Lung 6) | 2010-2011 | Phase 3 (C) | Afatinib | Inferior PFS |
Tumor specimen was required to be EGFR mutation-positive.
Chemotherapy
- Cisplatin (Platinol) 75 mg/m2 IV once on day 1
- Gemcitabine (Gemzar) 1000 mg/m2 IV once per day on days 1 & 8
21-day cycle for up to 6 cycles
Regimen variant #2, 75/1250
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Rossell et al. 2012 (EURTAC) | 2007-2011 | Phase 3 (C) | Erlotinib | Inferior PFS |
Wu et al. 2015 (ENSURE) | 2011-2012 | Phase 3 (C) | Erlotinib | Inferior PFS |
Note: Patients in EURTAC had EGFR exon 19 deletion or p.L858R mutation in exon 21.
Chemotherapy
- Cisplatin (Platinol) 75 mg/m2 IV over 30 minutes once on day 1
- Gemcitabine (Gemzar) 1250 mg/m2 IV over 2 hours once per day on days 1 & 8
21-day cycle for up to 4 cycles
References
- EURTAC: Rosell R, Carcereny E, Gervais R, Vergnenegre A, Massuti B, Felip E, Palmero R, Garcia-Gomez R, Pallares C, Sanchez JM, Porta R, Cobo M, Garrido P, Longo F, Moran T, Insa A, De Marinis F, Corre R, Bover I, Illiano A, Dansin E, de Castro J, Milella M, Reguart N, Altavilla G, Jimenez U, Provencio M, Moreno MA, Terrasa J, Muñoz-Langa J, Valdivia J, Isla D, Domine M, Molinier O, Mazieres J, Baize N, Garcia-Campelo R, Robinet G, Rodriguez-Abreu D, Lopez-Vivanco G, Gebbia V, Ferrera-Delgado L, Bombaron P, Bernabe R, Bearz A, Artal A, Cortesi E, Rolfo C, Sanchez-Ronco M, Drozdowskyj A, Queralt C, de Aguirre I, Ramirez JL, Sanchez JJ, Molina MA, Taron M, Paz-Ares L; Spanish Lung Cancer Group; Groupe Français de Pneumo-Cancérologie; Associazione Italiana Oncologia Toracica. Erlotinib versus standard chemotherapy as first-line treatment for European patients with advanced EGFR mutation-positive non-small-cell lung cancer (EURTAC): a multicentre, open-label, randomised phase 3 trial. Lancet Oncol. 2012 Mar;13(3):239-46. Epub 2012 Jan 26. link to original article contains protocol PubMed NCT00446225
- LUX-Lung 6: Wu YL, Zhou C, Hu CP, Feng J, Lu S, Huang Y, Li W, Hou M, Shi JH, Lee KY, Xu CR, Massey D, Kim M, Shi Y, Geater SL. Afatinib versus cisplatin plus gemcitabine for first-line treatment of Asian patients with advanced non-small-cell lung cancer harbouring EGFR mutations (LUX-Lung 6): an open-label, randomised phase 3 trial. Lancet Oncol. 2014 Feb;15(2):213-22. link to original article contains verified protocol PubMed NCT01121393
- Pooled update: Yang JC, Wu YL, Schuler M, Sebastian M, Popat S, Yamamoto N, Zhou C, Hu CP, O'Byrne K, Feng J, Lu S, Huang Y, Geater SL, Lee KY, Tsai CM, Gorbunova V, Hirsh V, Bennouna J, Orlov S, Mok T, Boyer M, Su WC, Lee KH, Kato T, Massey D, Shahidi M, Zazulina V, Sequist LV. Afatinib versus cisplatin-based chemotherapy for EGFR mutation-positive lung adenocarcinoma (LUX-Lung 3 and LUX-Lung 6): analysis of overall survival data from two randomised, phase 3 trials. Lancet Oncol. 2015 Feb;16(2):141-51. link to original article PubMed
- Pooled analysis: Yang JC, Sequist LV, Geater SL, Tsai CM, Mok TS, Schuler M, Yamamoto N, Yu CJ, Ou SH, Zhou C, Massey D, Zazulina V, Wu YL. Clinical activity of afatinib in patients with advanced non-small-cell lung cancer harbouring uncommon EGFR mutations: a combined post-hoc analysis of LUX-Lung 2, LUX-Lung 3, and LUX-Lung 6. Lancet Oncol. 2015 Jul;16(7):830-8. Epub 2015 Jun 4. link to original article PubMed
- Subgroup analysis: Schuler M, Wu YL, Hirsh V, O'Byrne K, Yamamoto N, Mok T, Popat S, Sequist LV, Massey D, Zazulina V, Yang JC. First-line afatinib versus chemotherapy in patients with non-small cell lung cancer and common epidermal growth factor receptor gene mutations and brain metastases. J Thorac Oncol. 2016 Mar;11(3):380-90. link to original article PubMed
- ENSURE: Wu YL, Zhou C, Liam CK, Wu G, Liu X, Zhong Z, Lu S, Cheng Y, Han B, Chen L, Huang C, Qin S, Zhu Y, Pan H, Liang H, Li E, Jiang G, How SH, Fernando MC, Zhang Y, Xia F, Zuo Y. First-line erlotinib versus gemcitabine/cisplatin in patients with advanced EGFR mutation-positive non-small-cell lung cancer: analyses from the phase III, randomized, open-label, ENSURE study. Ann Oncol. 2015 Sep;26(9):1883-9. Epub 2015 Jun 23. link to original article contains verified protocol PubMed NCT01342965
Cisplatin & Gemcitabine/Erlotinib
back to top |
Regimen
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Wu et al. 2013 (FASTACT-2) | 2009-2010 | Phase 3 (E-esc) | Cisplatin & Gemcitabine | Seems to have superior OS |
Note: this cohort was enriched for EGFR mutations and only those patients with an activating EGFR gene mutation were noted to have a treatment benefit in favor of the experimental arm.
Chemotherapy
- Cisplatin (Platinol) 75 mg/m2 IV once on day 1
- Gemcitabine (Gemzar) 1250 mg/m2 IV once per day on days 1 & 8
Targeted therapy
- Erlotinib (Tarceva) 150 mg PO once per day on days 15 to 28
28-day cycle for 4 cycles
References
- FASTACT-2: Wu YL, Lee JS, Thongprasert S, Yu CJ, Zhang L, Ladrera G, Srimuninnimit V, Sriuranpong V, Sandoval-Tan J, Zhu Y, Liao M, Zhou C, Pan H, Lee V, Chen YM, Sun Y, Margono B, Fuerte F, Chang GC, Seetalarom K, Wang J, Cheng A, Syahruddin E, Qian X, Ho J, Kurnianda J, Liu HE, Jin K, Truman M, Bara I, Mok T. Intercalated combination of chemotherapy and erlotinib for patients with advanced stage non-small-cell lung cancer (FASTACT-2): a randomised, double-blind trial. Lancet Oncol. 2013 Jul;14(8):777-86. Epub 2013 Jun 17. link to original article contains protocol PubMed NCT00883779
Cisplatin & Pemetrexed
back to top |
Pem-Cis: Pemetrexed & Cisplatin
Cis-Pem: Cisplatin & Pemetrexed
Regimen
FDA-recommended dose |
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Sequist et al. 2013 (LUX-Lung 3) | 2009-2011 | Phase 3 (C) | Afatinib | Inferior PFS |
Shi et al. 2017 (CONVINCE) | 2013-2014 | Phase 3 (C) | See link | See link |
Note: Patients in LUX-Lung 3 had adenocarcinoma with activating mutations in EGFR. Patients in CONVINCE had stage IIIB/IV lung adenocarcinoma and exon 19/21 EGFR mutations.
Chemotherapy
- Cisplatin (Platinol) 75 mg/m2 IV once on day 1, given second
- Pemetrexed (Alimta) 500 mg/m2 IV over 10 minutes once on day 1, given first
Supportive medications
- (as described in JMDB):
- Cyanocobalamin (Vitamin B12) 1000 mcg IM every 9 weeks, first dose prior to Pemetrexed (Alimta)
- Folic acid (Folate) 1 mg PO once per day
- In Sequist et al. 2013: Patients "received Folic acid (Folate), vitamin B12, and dexamethasone, as per package recommendations for Pemetrexed (Alimta)."
21-day cycle for 4 to 6 cycles
Subsequent treatment
- CONVINCE: Optional pemetrexed maintenance
References
- LUX-Lung 3: Sequist LV, Yang JC, Yamamoto N, O'Byrne K, Hirsh V, Mok T, Geater SL, Orlov S, Tsai CM, Boyer M, Su WC, Bennouna J, Kato T, Gorbunova V, Lee KH, Shah R, Massey D, Zazulina V, Shahidi M, Schuler M. Phase III study of afatinib or cisplatin plus pemetrexed in patients with metastatic lung adenocarcinoma with EGFR mutations. J Clin Oncol. 2013 Sep 20;31(27):3327-34. Epub 2013 Jul 1. link to original article contains verified protocol PubMed NCT00949650
- HRQoL analysis: Yang JC, Hirsh V, Schuler M, Yamamoto N, O'Byrne KJ, Mok TS, Zazulina V, Shahidi M, Lungershausen J, Massey D, Palmer M, Sequist LV. Symptom control and quality of life in LUX-Lung 3: a phase III study of afatinib or cisplatin/pemetrexed in patients with advanced lung adenocarcinoma with EGFR mutations. J Clin Oncol. 2013 Sep 20;31(27):3342-50. Epub 2013 Jul 1. link to original article contains verified protocol PubMed
- Pooled update: Yang JC, Wu YL, Schuler M, Sebastian M, Popat S, Yamamoto N, Zhou C, Hu CP, O'Byrne K, Feng J, Lu S, Huang Y, Geater SL, Lee KY, Tsai CM, Gorbunova V, Hirsh V, Bennouna J, Orlov S, Mok T, Boyer M, Su WC, Lee KH, Kato T, Massey D, Shahidi M, Zazulina V, Sequist LV. Afatinib versus cisplatin-based chemotherapy for EGFR mutation-positive lung adenocarcinoma (LUX-Lung 3 and LUX-Lung 6): analysis of overall survival data from two randomised, phase 3 trials. Lancet Oncol. 2015 Feb;16(2):141-51. link to original article PubMed
- Pooled analysis: Yang JC, Sequist LV, Geater SL, Tsai CM, Mok TS, Schuler M, Yamamoto N, Yu CJ, Ou SH, Zhou C, Massey D, Zazulina V, Wu YL. Clinical activity of afatinib in patients with advanced non-small-cell lung cancer harbouring uncommon EGFR mutations: a combined post-hoc analysis of LUX-Lung 2, LUX-Lung 3, and LUX-Lung 6. Lancet Oncol. 2015 Jul;16(7):830-8. Epub 2015 Jun 4. link to original article PubMed
- Subgroup analysis: Schuler M, Wu YL, Hirsh V, O'Byrne K, Yamamoto N, Mok T, Popat S, Sequist LV, Massey D, Zazulina V, Yang JC. First-line afatinib versus chemotherapy in patients with non-small cell lung cancer and common epidermal growth factor receptor gene mutations and brain metastases. J Thorac Oncol. 2016 Mar;11(3):380-90. link to original article PubMed
- CONVINCE: Shi YK, Wang L, Han BH, Li W, Yu P, Liu YP, Ding CM, Song X, Ma ZY, Ren XL, Feng JF, Zhang HL, Chen GY, Han XH, Wu N, Yao C, Song Y, Zhang SC, Song W, Liu XQ, Zhao SJ, Lin YC, Ye XQ, Li K, Shu YQ, Ding LM, Tan FL, Sun Y. First-line icotinib versus cisplatin/pemetrexed plus pemetrexed maintenance therapy for patients with advanced EGFR mutation-positive lung adenocarcinoma (CONVINCE): a phase 3, open-label, randomized study. Ann Oncol. 2017 Oct 1;28(10):2443-2450. link to original article contains verified protocol PubMed NCT01719536
Dacomitinib monotherapy
back to top |
Regimen
FDA-recommended dose |
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Ramalingam et al. 2012 (A7471028) | 2008-2010 | Randomized Phase II (E-switch-ic) | Erlotinib | Seems to have superior PFS Median PFS: 2.9 vs 1.9 mo (HR 0.66, 95% CI 0.47-0.91) |
Ramalingam et al. 2014 (ARCHER 1009) | 2011-2013 | Phase 3 (E-switch-ic) | Erlotinib | Did not meet primary endpoint of PFS Median PFS: 2.6 vs 2.6 mo (HR 0.94, 95% CI 0.80-1.10) |
Wu et al. 2017 (ARCHER 1050) | 2013-2015 | Phase 3 (E-RT-switch-ic) | Gefitinib | Seems to have superior OS1 Median OS: 34.1 vs 27 mo (HR 0.75, 95% CI 0.59-0.95) |
1Reported efficacy for ARCHER 1050 is based on the 2021 update.
Biomarker eligibility criteria
- A7471028 & ARCHER 1009: None
- ARCHER 1050: Activating mutations in EGFR
Targeted therapy
- Dacomitinib (Vizimpro) 45 mg PO once per day
Continued indefinitely
References
- A7471028: Ramalingam SS, Blackhall F, Krzakowski M, Barrios CH, Park K, Bover I, Seog Heo D, Rosell R, Talbot DC, Frank R, Letrent SP, Ruiz-Garcia A, Taylor I, Liang JQ, Campbell AK, O'Connell J, Boyer M. Randomized phase II study of dacomitinib (PF-00299804), an irreversible pan-human epidermal growth factor receptor inhibitor, versus erlotinib in patients with advanced non-small-cell lung cancer. J Clin Oncol. 2012 Sep 20;30(27):3337-44. Epub 2012 Jul 2. link to original article PubMed NCT00769067
- ARCHER 1009: Ramalingam SS, Jänne PA, Mok T, O'Byrne K, Boyer MJ, Von Pawel J, Pluzanski A, Shtivelband M, Docampo LI, Bennouna J, Zhang H, Liang JQ, Doherty JP, Taylor I, Mather CB, Goldberg Z, O'Connell J, Paz-Ares L. Dacomitinib versus erlotinib in patients with advanced-stage, previously treated non-small-cell lung cancer (ARCHER 1009): a randomised, double-blind, phase 3 trial. Lancet Oncol. 2014 Nov;15(12):1369-78. Epub 2014 Oct 15.link to original article PubMed NCT01360554
- ARCHER 1050: Wu YL, Cheng Y, Zhou X, Lee KH, Nakagawa K, Niho S, Tsuji F, Linke R, Rosell R, Corral J, Migliorino MR, Pluzanski A, Sbar EI, Wang T, White JL, Nadanaciva S, Sandin R, Mok TS. Dacomitinib versus gefitinib as first-line treatment for patients with EGFR-mutation-positive non-small-cell lung cancer (ARCHER 1050): a randomised, open-label, phase 3 trial. Lancet Oncol. 2017 Nov;18(11):1454-1466. Epub 2017 Sep 25. link to original article PubMed NCT01774721
- Update: Mok TS, Cheng Y, Zhou X, Lee KH, Nakagawa K, Niho S, Lee M, Linke R, Rosell R, Corral J, Migliorino MR, Pluzanski A, Sbar EI, Wang T, White JL, Wu YL. Improvement in overall survival in a randomized study that compared dacomitinib with gefitinib in patients with advanced non-small-cell lung cancer and EGFR-activating mutations. J Clin Oncol. 2018 Aug 1;36(22):2244-2250. Epub 2018 Jun 4. link to original article PubMed
- Update: Mok TS, Cheng Y, Zhou X, Lee KH, Nakagawa K, Niho S, Chawla A, Rosell R, Corral J, Migliorino MR, Pluzanski A, Noonan K, Tang Y, Pastel M, Wilner KD, Wu YL. Updated Overall Survival in a Randomized Study Comparing Dacomitinib with Gefitinib as First-Line Treatment in Patients with Advanced Non-Small-Cell Lung Cancer and EGFR-Activating Mutations. Drugs. 2021 Feb;81(2):257-266. link to original article link to PMC article PubMed
Erlotinib monotherapy
back to top |
Regimen variant #1, 150 mg/d
FDA-recommended dose |
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Rossell et al. 2012 (EURTAC) | 2007-2011 | Phase 3 (E-RT-switch-ooc) | 1. Carboplatin & Docetaxel 2. Carboplatin & Gemcitabine 3. Cisplatin & Docetaxel 4. Cisplatin & Gemcitabine |
Superior PFS Median PFS: 9.7 vs 5.2 mo (HR 0.37, 95% CI 0.25-0.54) |
Zhou et al. 2011 (CTONG-0802) | 2008-2009 | Phase 3 (E-switch-ooc) | Carboplatin & Gemcitabine | Superior PFS Median PFS: 13.1 vs 4.6 mo (HR 0.16, 95% CI 0.10-0.26) |
Ramalingam et al. 2012 (A7471028) | 2008-2010 | Randomized Phase II (C) | Dacomitinib | Seems to have inferior PFS |
Yang et al. 2017 (CTONG 0901) | 2009-2014 | Phase 3 (C) | Gefitinib | Did not meet primary endpoint of PFS |
Seto et al. 2014 (JO25567) | 2011-2012 | Randomized Phase II (C) | Erlotinib & Bevacizumab | Inferior PFS |
Wu et al. 2015 (ENSURE) | 2011-2012 | Phase 3 (E-switch-ooc) | Cisplatin & Gemcitabine | Superior PFS Median PFS: 11.0 vs 5.5 mo (HR 0.34, 95% CI 0.22-0.51) |
Ramalingam et al. 2014 (ARCHER 1009) | 2011-2013 | Phase 3 (C) | Dacomitinib | Did not meet primary endpoint of PFS |
Soria et al. 2017 (FLAURA) | 2014-2016 | Phase 3 (C) | Osimertinib | Seems to have inferior OS1 |
Saito et al. 2019 (NEJ026) | 2015-2016 | Phase 3 (C) | Erlotinib & Bevacizumab | Seems to have inferior PFS |
Kelly et al. 2019 (SOLARNSCLC) | 2016-2017 | Phase 3 (C) | Naquotinib | Did not meet primary endpoint of PFS |
Nakagawa et al. 2019 (RELAY) | 2016-2018 | Phase 3 (C) | Erlotinib & Ramucirumab | Inferior PFS |
1Reported efficacy for FLAURA is based on the 2019 update.
Note: these are all trials restricted to patients with EGFR-mutated lung cancer. Some trials of erlotinib in unselected populations nevertheless had high rates of EGFR-mutated lung cancers, due to the nature of the populations studied. See the main NSCLC page for these trials. SOLAR should not be confused with the trial by the same name in gastric cancer.
Targeted therapy
- Erlotinib (Tarceva) 150 mg PO once per day
Continued indefinitely
Regimen variant #2, low-dose
Study | Evidence |
---|---|
Yeo et al. 2010 | Retrospective |
Targeted therapy
- Erlotinib (Tarceva) 25 mg PO once per day
Continued indefinitely
References
- Retrospective: Yeo WL, Riely GJ, Yeap BY, Lau MW, Warner JL, Bodio K, Huberman MS, Kris MG, Tenen DG, Pao W, Kobayashi S, Costa DB. Erlotinib at a dose of 25 mg daily for non-small cell lung cancers with EGFR mutations. J Thorac Oncol. 2010 Jul;5(7):1048-53. link to PMC article PubMed
- CTONG-0802: Zhou C, Wu YL, Chen G, Feng J, Liu XQ, Wang C, Zhang S, Wang J, Zhou S, Ren S, Lu S, Zhang L, Hu C, Hu C, Luo Y, Chen L, Ye M, Huang J, Zhi X, Zhang Y, Xiu Q, Ma J, Zhang L, You C. Erlotinib versus chemotherapy as first-line treatment for patients with advanced EGFR mutation-positive non-small-cell lung cancer (OPTIMAL, CTONG-0802): a multicentre, open-label, randomised, phase 3 study. Lancet Oncol. 2011 Aug;12(8):735-42. Epub 2011 Jul 23. link to original article contains protocol PubMed NCT00874419
- Update: Zhou C, Wu YL, Chen G, Feng J, Liu XQ, Wang C, Zhang S, Wang J, Zhou S, Ren S, Lu S, Zhang L, Hu C, Hu C, Luo Y, Chen L, Ye M, Huang J, Zhi X, Zhang Y, Xiu Q, Ma J, Zhang L, You C. Final overall survival results from a randomised, phase III study of erlotinib versus chemotherapy as first-line treatment of EGFR mutation-positive advanced non-small-cell lung cancer (OPTIMAL, CTONG-0802). Ann Oncol. 2015 Sep;26(9):1877-83. Epub 2015 Jul 3. link to original article PubMed
- EURTAC: Rosell R, Carcereny E, Gervais R, Vergnenegre A, Massuti B, Felip E, Palmero R, Garcia-Gomez R, Pallares C, Sanchez JM, Porta R, Cobo M, Garrido P, Longo F, Moran T, Insa A, De Marinis F, Corre R, Bover I, Illiano A, Dansin E, de Castro J, Milella M, Reguart N, Altavilla G, Jimenez U, Provencio M, Moreno MA, Terrasa J, Muñoz-Langa J, Valdivia J, Isla D, Domine M, Molinier O, Mazieres J, Baize N, Garcia-Campelo R, Robinet G, Rodriguez-Abreu D, Lopez-Vivanco G, Gebbia V, Ferrera-Delgado L, Bombaron P, Bernabe R, Bearz A, Artal A, Cortesi E, Rolfo C, Sanchez-Ronco M, Drozdowskyj A, Queralt C, de Aguirre I, Ramirez JL, Sanchez JJ, Molina MA, Taron M, Paz-Ares L; Spanish Lung Cancer Group; Groupe Français de Pneumo-Cancérologie; Associazione Italiana Oncologia Toracica. Erlotinib versus standard chemotherapy as first-line treatment for European patients with advanced EGFR mutation-positive non-small-cell lung cancer (EURTAC): a multicentre, open-label, randomised phase 3 trial. Lancet Oncol. 2012 Mar;13(3):239-46. Epub 2012 Jan 26. link to original article contains protocol PubMed NCT00446225
- A7471028: Ramalingam SS, Blackhall F, Krzakowski M, Barrios CH, Park K, Bover I, Seog Heo D, Rosell R, Talbot DC, Frank R, Letrent SP, Ruiz-Garcia A, Taylor I, Liang JQ, Campbell AK, O'Connell J, Boyer M. Randomized phase II study of dacomitinib (PF-00299804), an irreversible pan-human epidermal growth factor receptor inhibitor, versus erlotinib in patients with advanced non-small-cell lung cancer. J Clin Oncol. 2012 Sep 20;30(27):3337-44. Epub 2012 Jul 2. link to original article link to PMC article contains protocol PubMed NCT00769067
- JO25567: Seto T, Kato T, Nishio M, Goto K, Atagi S, Hosomi Y, Yamamoto N, Hida T, Maemondo M, Nakagawa K, Nagase S, Okamoto I, Yamanaka T, Tajima K, Harada R, Fukuoka M, Yamamoto N. Erlotinib alone or with bevacizumab as first-line therapy in patients with advanced non-squamous non-small-cell lung cancer harbouring EGFR mutations (JO25567): an open-label, randomised, multicentre, phase 2 study. Lancet Oncol. 2014 Oct;15(11):1236-44. Epub 2014 Aug 27. Erratum in: Lancet Oncol. 2014 Oct;15(11):e475. link to original article contains protocol PubMed JapicCTI-111390
- ARCHER 1009: Ramalingam SS, Jänne PA, Mok T, O'Byrne K, Boyer MJ, Von Pawel J, Pluzanski A, Shtivelband M, Docampo LI, Bennouna J, Zhang H, Liang JQ, Doherty JP, Taylor I, Mather CB, Goldberg Z, O'Connell J, Paz-Ares L. Dacomitinib versus erlotinib in patients with advanced-stage, previously treated non-small-cell lung cancer (ARCHER 1009): a randomised, double-blind, phase 3 trial. Lancet Oncol. 2014 Nov;15(12):1369-78. Epub 2014 Oct 15. link to original article contains protocol PubMed NCT01360554
- ENSURE: Wu YL, Zhou C, Liam CK, Wu G, Liu X, Zhong Z, Lu S, Cheng Y, Han B, Chen L, Huang C, Qin S, Zhu Y, Pan H, Liang H, Li E, Jiang G, How SH, Fernando MC, Zhang Y, Xia F, Zuo Y. First-line erlotinib versus gemcitabine/cisplatin in patients with advanced EGFR mutation-positive non-small-cell lung cancer: analyses from the phase III, randomized, open-label, ENSURE study. Ann Oncol. 2015 Sep;26(9):1883-9. Epub 2015 Jun 23. link to original article contains verified protocol PubMed NCT01342965
- CTONG 0901: Yang JJ, Zhou Q, Yan HH, Zhang XC, Chen HJ, Tu HY, Wang Z, Xu CR, Su J, Wang BC, Jiang BY, Bai XY, Zhong WZ, Yang XN, Wu YL. A phase III randomised controlled trial of erlotinib vs gefitinib in advanced non-small cell lung cancer with EGFR mutations. Br J Cancer. 2017 Feb 28;116(5):568-574. Epub 2017 Jan 19. link to original article contains protocol link to PMC article PubMed NCT01024413
- FLAURA: Soria JC, Ohe Y, Vansteenkiste J, Reungwetwattana T, Chewaskulyong B, Lee KH, Dechaphunkul A, Imamura F, Nogami N, Kurata T, Okamoto I, Zhou C, Cho BC, Cheng Y, Cho EK, Voon PJ, Planchard D, Su WC, Gray JE, Lee SM, Hodge R, Marotti M, Rukazenkov Y, Ramalingam SS; FLAURA Investigators. Osimertinib in untreated EGFR-mutated advanced non-small-cell lung cancer. N Engl J Med. 2018 Jan 11;378(2):113-125. Epub 2017 Nov 18. link to original article contains verified protocol PubMed NCT02296125
- Subgroup analysis: Reungwetwattana T, Nakagawa K, Cho BC, Cobo M, Cho EK, Bertolini A, Bohnet S, Zhou C, Lee KH, Nogami N, Okamoto I, Leighl N, Hodge R, McKeown A, Brown AP, Rukazenkov Y, Ramalingam SS, Vansteenkiste J. CNS response to osimertinib versus standard epidermal growth factor receptor tyrosine kinase inhibitors in patients with untreated EGFR-mutated advanced non-small-cell lung cancer. J Clin Oncol. 2018 Nov 20;36(33):3290-7. Epub 2018 Aug 28. link to original article PubMed
- Update: Ramalingam SS, Vansteenkiste J, Planchard D, Cho BC, Gray JE, Ohe Y, Zhou C, Reungwetwattana T, Cheng Y, Chewaskulyong B, Shah R, Cobo M, Lee KH, Cheema P, Tiseo M, John T, Lin MC, Imamura F, Kurata T, Todd A, Hodge R, Saggese M, Rukazenkov Y, Soria JC; FLAURA Investigators. Overall survival with osimertinib in untreated, EGFR-mutated advanced NSCLC. N Engl J Med. 2020 Jan 2;382(1):41-50. Epub 2019 Nov 21. link to original article PubMed
- NEJ026: Saito H, Fukuhara T, Furuya N, Watanabe K, Sugawara S, Iwasawa S, Tsunezuka Y, Yamaguchi O, Okada M, Yoshimori K, Nakachi I, Gemma A, Azuma K, Kurimoto F, Tsubata Y, Fujita Y, Nagashima H, Asai G, Watanabe S, Miyazaki M, Hagiwara K, Nukiwa T, Morita S, Kobayashi K, Maemondo M. Erlotinib plus bevacizumab versus erlotinib alone in patients with EGFR-positive advanced non-squamous non-small-cell lung cancer (NEJ026): interim analysis of an open-label, randomised, multicentre, phase 3 trial. Lancet Oncol. 2019 May;20(5):625-635. Epub 2019 Apr 8. link to original article contains protocol PubMed UMIN000017069
- SOLAR: Kelly RJ, Shepherd FA, Krivoshik A, Jie F, Horn L. A phase 3, randomized, open-label study of ASP8273 versus erlotinib or gefitinib in patients with advanced stage IIIB/IV non-small cell lung cancer. Ann Oncol. 2019 Jul 1;30(7):1127-1133. Epub 2019 May 9. link to original article link to PMC article PubMed NCT02588261
- RELAY: Nakagawa K, Garon EB, Seto T, Nishio M, Ponce Aix S, Paz-Ares L, Chiu CH, Park K, Novello S, Nadal E, Imamura F, Yoh K, Shih JY, Au KH, Moro-Sibilot D, Enatsu S, Zimmermann A, Frimodt-Moller B, Visseren-Grul C, Reck M; RELAY Study Investigators. Ramucirumab plus erlotinib in patients with untreated, EGFR-mutated, advanced non-small-cell lung cancer (RELAY): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2019 Dec;20(12):1655-1669. Epub 2019 Oct 4. link to original article contains protocol PubMed NCT02411448
Erlotinib & Bevacizumab
back to top |
Regimen
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Seto et al. 2014 (JO25567) | 2011-2012 | Randomized Phase II (E-esc) | Erlotinib | Superior PFS Median PFS: 16 vs 9.7 mo (HR 0.54, 95% CI 0.36-0.79) |
Saito et al. 2019 (NEJ026) | 2015-2016 | Phase 3 (E-esc) | Erlotinib | Seems to have superior PFS Median PFS: 16.9 vs 13.3 mo (HR 0.61, 95% CI 0.42-0.88) |
Targeted therapy
- Erlotinib (Tarceva) 150 mg PO once per day
- Bevacizumab (Avastin) 15 mg/kg IV once on day 1
21-day cycles
References
- JO25567: Seto T, Kato T, Nishio M, Goto K, Atagi S, Hosomi Y, Yamamoto N, Hida T, Maemondo M, Nakagawa K, Nagase S, Okamoto I, Yamanaka T, Tajima K, Harada R, Fukuoka M, Yamamoto N. Erlotinib alone or with bevacizumab as first-line therapy in patients with advanced non-squamous non-small-cell lung cancer harbouring EGFR mutations (JO25567): an open-label, randomised, multicentre, phase 2 study. Lancet Oncol. 2014 Oct;15(11):1236-44. Epub 2014 Aug 27. Erratum in: Lancet Oncol. 2014 Oct;15(11):e475. link to original article contains protocol PubMed JapicCTI-111390
- NEJ026: Saito H, Fukuhara T, Furuya N, Watanabe K, Sugawara S, Iwasawa S, Tsunezuka Y, Yamaguchi O, Okada M, Yoshimori K, Nakachi I, Gemma A, Azuma K, Kurimoto F, Tsubata Y, Fujita Y, Nagashima H, Asai G, Watanabe S, Miyazaki M, Hagiwara K, Nukiwa T, Morita S, Kobayashi K, Maemondo M. Erlotinib plus bevacizumab versus erlotinib alone in patients with EGFR-positive advanced non-squamous non-small-cell lung cancer (NEJ026): interim analysis of an open-label, randomised, multicentre, phase 3 trial. Lancet Oncol. 2019 May;20(5):625-635. Epub 2019 Apr 8. link to original article contains protocol PubMed UMIN000017069
Erlotinib & Ramucirumab
back to top |
Regimen
FDA-recommended dose |
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Nakagawa et al. 2019 (RELAY) | 2016-2018 | Phase 3 (E-RT-esc) | Erlotinib | Superior PFS Median PFS: 19.4 mo vs 12.4 mo (HR 0.59, 95% CI 0.46-0.76) |
Note: the FDA-recommended dose is only provided for ramucirumab.
Targeted therapy
- Erlotinib (Tarceva) 150 mg PO once per day
- Ramucirumab (Cyramza) 10 mg/kg IV once on day 1
14-day cycles
References
- RELAY: Nakagawa K, Garon EB, Seto T, Nishio M, Ponce Aix S, Paz-Ares L, Chiu CH, Park K, Novello S, Nadal E, Imamura F, Yoh K, Shih JY, Au KH, Moro-Sibilot D, Enatsu S, Zimmermann A, Frimodt-Moller B, Visseren-Grul C, Reck M; RELAY Study Investigators. Ramucirumab plus erlotinib in patients with untreated, EGFR-mutated, advanced non-small-cell lung cancer (RELAY): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2019 Dec;20(12):1655-1669. Epub 2019 Oct 4. link to original article contains protocol PubMed NCT02411448
GCP
back to top |
GCP: Gefitinib, Carboplatin, Pemetrexed
Regimen variant #1, 4 cycles
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Noronha et al. 2019 | 2016-2018 | Phase 3 (E-esc) | Gefitinib | Superior OS |
Targeted therapy
- Gefitinib (Iressa) 250 mg PO once per day
Chemotherapy
- Carboplatin (Paraplatin) AUC 5 IV once on day 1
- Pemetrexed (Alimta) 500 mg/m2 IV once on day 1
21-day cycle for 4 cycles
Subsequent treatment
- Gefitinib & Pemetrexed maintenance
Regimen variant #2, 6 cycles
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Hosomi et al. 2019 (NEJ009) | 2011-2015 | Phase 3 (E-esc) | Gefitinib | Seems to have superior OS |
Targeted therapy
- Gefitinib (Iressa) 250 mg PO once per day
Chemotherapy
- Carboplatin (Paraplatin) AUC 5 IV once on day 1
- Pemetrexed (Alimta) 500 mg/m2 IV once on day 1
21-day cycle for up to 6 cycles
Subsequent treatment
- Gefitinib & Pemetrexed maintenance
References
- NEJ009: Hosomi Y, Morita S, Sugawara S, Kato T, Fukuhara T, Gemma A, Takahashi K, Fujita Y, Harada T, Minato K, Takamura K, Hagiwara K, Kobayashi K, Nukiwa T, Inoue A; North-East Japan Study Group. Gefitinib Alone Versus Gefitinib Plus Chemotherapy for Non-Small-Cell Lung Cancer With Mutated Epidermal Growth Factor Receptor: NEJ009 Study. J Clin Oncol. 2020 Jan 10;38(2):115-123. Epub 2019 Nov 4. link to original article contains verified protocol PubMed UMIN000006340
- Noronha V, Patil VM, Joshi A, Menon N, Chougule A, Mahajan A, Janu A, Purandare N, Kumar R, More S, Goud S, Kadam N, Daware N, Bhattacharjee A, Shah S, Yadav A, Trivedi V, Behel V, Dutt A, Banavali SD, Prabhash K. Gefitinib Versus Gefitinib Plus Pemetrexed and Carboplatin Chemotherapy in EGFR-Mutated Lung Cancer. J Clin Oncol. 2020 Jan 10;38(2):124-136. Epub 2019 Aug 14. link to original article contains verified protocol PubMed
Gefitinib monotherapy
back to top |
Regimen
FDA-recommended dose |
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Mitsudomi et al. 2009 (WJTOG3405) | 2006-2009 | Phase 3 (E-switch-ooc) | Cisplatin & Docetaxel | Superior PFS |
Maemondo et al. 2010 (NEJ002) | 2006-2009 | Phase 3 (E-switch-ooc) | Carboplatin & Paclitaxel | Superior PFS Median PFS 10.8 vs 5.4 mo (HR 0.30, 95% CI 0.22-0.41) |
Urata et al. 2016 (WJOG 5108L) | 2009-2012 | Phase 3 (C) | Erlotinib | Inconclusive whether non-inferior PFS |
Yang et al. 2017 (CTONG 0901) | 2009-2014 | Phase 3 (C) | Erlotinib | Did not meet primary endpoint of PFS |
Douillard et al. 2014 (IFUM) | 2010-2012 | Phase IV (RT) | ORR: 70% (95% CI: 60.5–78) | |
Park et al. 2016 (LUX-Lung 7) | 2011-2013 | Randomized Phase II (C) | Afatinib | Seems to have inferior PFS |
Hosomi et al. 2019 (NEJ009) | 2011-2015 | Phase 3 (C) | GCP | Seems to have inferior OS |
Cheng et al. 2016 (JMIT) | 2012-2013 | Randomized Phase II (C) | P+G | Seems to have inferior PFS |
Patil et al. 2017 | 2012-2016 | Phase 3 (E-switch-ooc) | Carboplatin & Pemetrexed, then Pem maint. | Superior PFS |
Wu et al. 2017 (ARCHER 1050) | 2013-2015 | Phase 3 (C) | Dacomitinib | Seems to have inferior OS1 |
Soria et al. 2017 (FLAURA) | 2014-2016 | Phase 3 (C) | Osimertinib | Seems to have inferior OS2 |
Noronha et al. 2019 | 2016-2018 | Phase 3 (C) | GCP | Inferior OS |
1Reported efficacy for ARCHER 1050 is based on the 2021 update.
2Reported efficacy for FLAURA is based on the 2019 update.
Note: these are all trials restricted to EGFR-mutated lung cancer, with the exception of WJOG 5108L, which nevertheless had 72% EGFR-mutated patients.
Targeted therapy
- Gefitinib (Iressa) 250 mg PO once per day
Continued indefinitely
References
- WJTOG3405: Mitsudomi T, Morita S, Yatabe Y, Negoro S, Okamoto I, Tsurutani J, Seto T, Satouchi M, Tada H, Hirashima T, Asami K, Katakami N, Takada M, Yoshioka H, Shibata K, Kudoh S, Shimizu E, Saito H, Toyooka S, Nakagawa K, Fukuoka M; West Japan Thoracic Oncology Group. Gefitinib versus cisplatin plus docetaxel in patients with non-small-cell lung cancer harbouring mutations of the epidermal growth factor receptor (WJTOG3405): an open label, randomised phase 3 trial. Lancet Oncol. 2010 Feb;11(2):121-8. Epub 2009 Dec 18. link to original article contains verified protocol PubMed UMIN000000539
- Update: Yoshioka H, Shimokawa M, Seto T, Morita S, Yatabe Y, Okamoto I, Tsurutani J, Satouchi M, Hirashima T, Atagi S, Shibata K, Saito H, Toyooka S, Yamamoto N, Nakagawa K, Mitsudomi T. Final overall survival results of WJTOG3405, a randomized phase III trial comparing gefitinib versus cisplatin with docetaxel as the first-line treatment for patients with stage IIIB/IV or postoperative recurrent EGFR mutation-positive non-small-cell lung cancer. Ann Oncol. 2019 Dec 1;30(12):1978-1984. link to original article PubMed
- NEJ002: Maemondo M, Inoue A, Kobayashi K, Sugawara S, Oizumi S, Isobe H, Gemma A, Harada M, Yoshizawa H, Kinoshita I, Fujita Y, Okinaga S, Hirano H, Yoshimori K, Harada T, Ogura T, Ando M, Miyazawa H, Tanaka T, Saijo Y, Hagiwara K, Morita S, Nukiwa T; North-East Japan Study Group. Gefitinib or chemotherapy for non-small-cell lung cancer with mutated EGFR. N Engl J Med. 2010 Jun 24;362(25):2380-8. link to original article contains verified protocol PubMed UMIN000000376
- HRQoL analysis: Oizumi S, Kobayashi K, Inoue A, Maemondo M, Sugawara S, Yoshizawa H, Isobe H, Harada M, Kinoshita I, Okinaga S, Kato T, Harada T, Gemma A, Saijo Y, Yokomizo Y, Morita S, Hagiwara K, Nukiwa T. Quality of life with gefitinib in patients with EGFR-mutated non-small cell lung cancer: quality of life analysis of North East Japan Study Group 002 Trial. Oncologist. 2012;17(6):863-70. Epub 2012 May 11. link to original article link to PMC article PubMed
- Update: Inoue A, Kobayashi K, Maemondo M, Sugawara S, Oizumi S, Isobe H, Gemma A, Harada M, Yoshizawa H, Kinoshita I, Fujita Y, Okinaga S, Hirano H, Yoshimori K, Harada T, Saijo Y, Hagiwara K, Morita S, Nukiwa T; North-East Japan Study Group. Updated overall survival results from a randomized phase III trial comparing gefitinib with carboplatin-paclitaxel for chemo-naïve non-small cell lung cancer with sensitive EGFR gene mutations (NEJ002). Ann Oncol. 2013 Jan;24(1):54-9. Epub 2012 Sep 11. link to original article PubMed
- IFUM: Douillard JY, Ostoros G, Cobo M, Ciuleanu T, McCormack R, Webster A, Milenkova T. First-line gefitinib in Caucasian EGFR mutation-positive NSCLC patients: a phase-IV, open-label, single-arm study. Br J Cancer. 2014 Jan 7;110(1):55-62. Epub 2013 Nov 21. link to original article contains verified protocol link to PMC article PubMed NCT01203917
- LUX-Lung 7: Park K, Tan EH, O'Byrne K, Zhang L, Boyer M, Mok T, Hirsh V, Yang JC, Lee KH, Lu S, Shi Y, Kim SW, Laskin J, Kim DW, Arvis CD, Kölbeck K, Laurie SA, Tsai CM, Shahidi M, Kim M, Massey D, Zazulina V, Paz-Ares L. Afatinib versus gefitinib as first-line treatment of patients with EGFR mutation-positive non-small-cell lung cancer (LUX-Lung 7): a phase 2B, open-label, randomised controlled trial. Lancet Oncol. 2016 May;17(5):577-89. Epub 2016 Apr 12. link to original article contains protocol PubMed NCT01466660
- WJOG 5108L: Urata Y, Katakami N, Morita S, Kaji R, Yoshioka H, Seto T, Satouchi M, Iwamoto Y, Kanehara M, Fujimoto D, Ikeda N, Murakami H, Daga H, Oguri T, Goto I, Imamura F, Sugawara S, Saka H, Nogami N, Negoro S, Nakagawa K, Nakanishi Y. Randomized phase III study comparing gefitinib with erlotinib in patients with previously treated advanced lung adenocarcinoma: WJOG 5108L. J Clin Oncol. 2016 Sep 20;34(27):3248-57. Epub 2016 Mar 28. link to original article contains verified protocol PubMed UMIN000002014
- JMIT: Cheng Y, Murakami H, Yang PC, He J, Nakagawa K, Kang JH, Kim JH, Wang X, Enatsu S, Puri T, Orlando M, Yang JC. Randomized phase II trial of gefitinib with and without pemetrexed as first-line therapy in patients with advanced nonsquamous non-small-cell lung cancer with activating epidermal growth factor receptor mutations. J Clin Oncol. 2016 Sep 20;34(27):3258-66. Epub 2016 Aug 9. link to original article contains verified protocol PubMed NCT01469000
- CTONG 0901: Yang JJ, Zhou Q, Yan HH, Zhang XC, Chen HJ, Tu HY, Wang Z, Xu CR, Su J, Wang BC, Jiang BY, Bai XY, Zhong WZ, Yang XN, Wu YL. A phase III randomised controlled trial of erlotinib vs gefitinib in advanced non-small cell lung cancer with EGFR mutations. Br J Cancer. 2017 Feb 28;116(5):568-574. Epub 2017 Jan 19. link to original article contains protocol link to PMC article PubMed NCT01024413
- Patil VM, Noronha V, Joshi A, Choughule AB, Bhattacharjee A, Kumar R, Goud S, More S, Ramaswamy A, Karpe A, Pande N, Chandrasekharan A, Goel A, Talreja V, Mahajan A, Janu A, Purandare N, Prabhash K. Phase III study of gefitinib or pemetrexed with carboplatin in EGFR-mutated advanced lung adenocarcinoma. ESMO Open. 2017 Apr 27;2(1):e000168. link to original article link to PMC article PubMed
- ARCHER 1050: Wu YL, Cheng Y, Zhou X, Lee KH, Nakagawa K, Niho S, Tsuji F, Linke R, Rosell R, Corral J, Migliorino MR, Pluzanski A, Sbar EI, Wang T, White JL, Nadanaciva S, Sandin R, Mok TS. Dacomitinib versus gefitinib as first-line treatment for patients with EGFR-mutation-positive non-small-cell lung cancer (ARCHER 1050): a randomised, open-label, phase 3 trial. Lancet Oncol. 2017 Nov;18(11):1454-1466. Epub 2017 Sep 25. link to original article contains verified protocol PubMed NCT01774721
- Update: Mok TS, Cheng Y, Zhou X, Lee KH, Nakagawa K, Niho S, Lee M, Linke R, Rosell R, Corral J, Migliorino MR, Pluzanski A, Sbar EI, Wang T, White JL, Wu YL. Improvement in overall survival in a randomized study that compared dacomitinib with gefitinib in patients with advanced non-small-cell lung cancer and EGFR-activating mutations. J Clin Oncol. 2018 Aug 1;36(22):2244-2250. Epub 2018 Jun 4. link to original article PubMed
- Update: Mok TS, Cheng Y, Zhou X, Lee KH, Nakagawa K, Niho S, Chawla A, Rosell R, Corral J, Migliorino MR, Pluzanski A, Noonan K, Tang Y, Pastel M, Wilner KD, Wu YL. Updated Overall Survival in a Randomized Study Comparing Dacomitinib with Gefitinib as First-Line Treatment in Patients with Advanced Non-Small-Cell Lung Cancer and EGFR-Activating Mutations. Drugs. 2021 Feb;81(2):257-266. link to original article link to PMC article PubMed
- FLAURA: Soria JC, Ohe Y, Vansteenkiste J, Reungwetwattana T, Chewaskulyong B, Lee KH, Dechaphunkul A, Imamura F, Nogami N, Kurata T, Okamoto I, Zhou C, Cho BC, Cheng Y, Cho EK, Voon PJ, Planchard D, Su WC, Gray JE, Lee SM, Hodge R, Marotti M, Rukazenkov Y, Ramalingam SS; FLAURA Investigators. Osimertinib in untreated EGFR-mutated advanced non-small-cell lung cancer. N Engl J Med. 2018 Jan 11;378(2):113-125. Epub 2017 Nov 18. link to original article contains verified protocol PubMed NCT02296125
- Subgroup analysis: Reungwetwattana T, Nakagawa K, Cho BC, Cobo M, Cho EK, Bertolini A, Bohnet S, Zhou C, Lee KH, Nogami N, Okamoto I, Leighl N, Hodge R, McKeown A, Brown AP, Rukazenkov Y, Ramalingam SS, Vansteenkiste J. CNS response to osimertinib versus standard epidermal growth factor receptor tyrosine kinase inhibitors in patients with untreated EGFR-mutated advanced non-small-cell lung cancer. J Clin Oncol. 2018 Nov 20;36(33):3290-7. Epub 2018 Aug 28. link to original article PubMed
- Update: Ramalingam SS, Vansteenkiste J, Planchard D, Cho BC, Gray JE, Ohe Y, Zhou C, Reungwetwattana T, Cheng Y, Chewaskulyong B, Shah R, Cobo M, Lee KH, Cheema P, Tiseo M, John T, Lin MC, Imamura F, Kurata T, Todd A, Hodge R, Saggese M, Rukazenkov Y, Soria JC; FLAURA Investigators. Overall survival with osimertinib in untreated, EGFR-mutated advanced NSCLC. N Engl J Med. 2020 Jan 2;382(1):41-50. Epub 2019 Nov 21. link to original article PubMed
- NEJ009: Hosomi Y, Morita S, Sugawara S, Kato T, Fukuhara T, Gemma A, Takahashi K, Fujita Y, Harada T, Minato K, Takamura K, Hagiwara K, Kobayashi K, Nukiwa T, Inoue A; North-East Japan Study Group. Gefitinib Alone Versus Gefitinib Plus Chemotherapy for Non-Small-Cell Lung Cancer With Mutated Epidermal Growth Factor Receptor: NEJ009 Study. J Clin Oncol. 2020 Jan 10;38(2):115-123. Epub 2019 Nov 4. link to original article contains verified protocol PubMed UMIN000006340
- Noronha V, Patil VM, Joshi A, Menon N, Chougule A, Mahajan A, Janu A, Purandare N, Kumar R, More S, Goud S, Kadam N, Daware N, Bhattacharjee A, Shah S, Yadav A, Trivedi V, Behel V, Dutt A, Banavali SD, Prabhash K. Gefitinib Versus Gefitinib Plus Pemetrexed and Carboplatin Chemotherapy in EGFR-Mutated Lung Cancer. J Clin Oncol. 2020 Jan 10;38(2):124-136. Epub 2019 Aug 14. link to original article contains verified protocol PubMed
Gefitinib & Pemetrexed
back to top |
P+G: Pemetrexed and Gefitinib
Regimen
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Cheng et al. 2016 (JMIT) | 2012-2013 | Randomized Phase II (E-esc) | Gefitinib | Seems to have superior PFS |
Targeted therapy
- Gefitinib (Iressa) 250 mg PO once per day
Chemotherapy
- Pemetrexed (Alimta) 500 mg IV once on day 1
21-day cycles
References
- JMIT: Cheng Y, Murakami H, Yang PC, He J, Nakagawa K, Kang JH, Kim JH, Wang X, Enatsu S, Puri T, Orlando M, Yang JC. Randomized phase II trial of gefitinib with and without pemetrexed as first-line therapy in patients with advanced nonsquamous non-small-cell lung cancer with activating epidermal growth factor receptor mutations. J Clin Oncol. 2016 Sep 20;34(27):3258-66. Epub 2016 Aug 9. link to original article contains verified protocol PubMed NCT01469000
Icotinib monotherapy
back to top |
Regimen
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Shi et al. 2017 (CONVINCE) | 2013-2014 | Phase 3 (E-switch-ooc) | Cisplatin & Pemetrexed x 4, then Pemetrexed maintenance | Superior PFS |
Note: this drug is only approved in China; eligible patients had stage IIIB/IV lung adenocarcinoma.
Biomarker eligibility criteria
- EGFR exon 19 or 21 mutations
Targeted therapy
- Icotinib (Conmana) 125 mg PO three times per day
Continued indefinitely
References
- CONVINCE: Shi YK, Wang L, Han BH, Li W, Yu P, Liu YP, Ding CM, Song X, Ma ZY, Ren XL, Feng JF, Zhang HL, Chen GY, Han XH, Wu N, Yao C, Song Y, Zhang SC, Song W, Liu XQ, Zhao SJ, Lin YC, Ye XQ, Li K, Shu YQ, Ding LM, Tan FL, Sun Y. First-line icotinib versus cisplatin/pemetrexed plus pemetrexed maintenance therapy for patients with advanced EGFR mutation-positive lung adenocarcinoma (CONVINCE): a phase 3, open-label, randomized study. Ann Oncol. 2017 Oct 1;28(10):2443-2450. link to original article contains verified protocol PubMed NCT01719536
Osimertinib monotherapy
back to top |
Regimen
FDA-recommended dose |
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Soria et al. 2017 (FLAURA) | 2014-2016 | Phase 3 (E-RT-switch-ic) | 1. Erlotinib 2. Gefitinib |
Seems to have superior OS1 Median OS: 38.6 vs 31.8 mo (HR 0.80, 95% CI 0.64-1.00) |
1Reported efficacy is based on the 2019 update.
Biomarker eligibility criteria
- EGFR exon 19 deletion or p.L858R mutation
Targeted therapy
- Osimertinib (Tagrisso) 80 mg PO once per day
Continued indefinitely
References
- FLAURA: Soria JC, Ohe Y, Vansteenkiste J, Reungwetwattana T, Chewaskulyong B, Lee KH, Dechaphunkul A, Imamura F, Nogami N, Kurata T, Okamoto I, Zhou C, Cho BC, Cheng Y, Cho EK, Voon PJ, Planchard D, Su WC, Gray JE, Lee SM, Hodge R, Marotti M, Rukazenkov Y, Ramalingam SS; FLAURA Investigators. Osimertinib in untreated EGFR-mutated advanced non-small-cell lung cancer. N Engl J Med. 2018 Jan 11;378(2):113-125. Epub 2017 Nov 18. link to original article contains verified protocol PubMed NCT02296125
- Subgroup analysis: Reungwetwattana T, Nakagawa K, Cho BC, Cobo M, Cho EK, Bertolini A, Bohnet S, Zhou C, Lee KH, Nogami N, Okamoto I, Leighl N, Hodge R, McKeown A, Brown AP, Rukazenkov Y, Ramalingam SS, Vansteenkiste J. CNS response to osimertinib versus standard epidermal growth factor receptor tyrosine kinase inhibitors in patients with untreated EGFR-mutated advanced non-small-cell lung cancer. J Clin Oncol. 2018 Nov 20;36(33):3290-7. Epub 2018 Aug 28. link to original article PubMed
- Update: Ramalingam SS, Vansteenkiste J, Planchard D, Cho BC, Gray JE, Ohe Y, Zhou C, Reungwetwattana T, Cheng Y, Chewaskulyong B, Shah R, Cobo M, Lee KH, Cheema P, Tiseo M, John T, Lin MC, Imamura F, Kurata T, Todd A, Hodge R, Saggese M, Rukazenkov Y, Soria JC; FLAURA Investigators. Overall survival with osimertinib in untreated, EGFR-mutated advanced NSCLC. N Engl J Med. 2020 Jan 2;382(1):41-50. Epub 2019 Nov 21. link to original article PubMed
Advanced or metastatic disease, EGFR inhibitor-exposed
Afatinib monotherapy
back to top |
Regimen
Study | Years of enrollment | Evidence | Efficacy |
---|---|---|---|
Katakami et al. 2013 (LUX-Lung 4) | 2009-2011 | Phase II | ORR: 8% (95% CI: 3-18) |
In LUX-Lung 4, 72.6% of patients were EGFR mutation positive. This was third or fourth line therapy for participants, who had progressed while receiving erlotinib and/or gefitinib and had received one or two previous lines of chemotherapy, including at least one platinum-based regimen.
Targeted therapy
- Afatinib (Gilotrif) 50 mg PO once per day, given 1 hour before eating food
Continued indefinitely
References
- LUX-Lung 4: Katakami N, Atagi S, Goto K, Hida T, Horai T, Inoue A, Ichinose Y, Koboyashi K, Takeda K, Kiura K, Nishio K, Seki Y, Ebisawa R, Shahidi M, Yamamoto N. LUX-Lung 4: a phase II trial of afatinib in patients with advanced non-small-cell lung cancer who progressed during prior treatment with erlotinib, gefitinib, or both. J Clin Oncol. 2013 Sep 20;31(27):3335-41. Epub 2013 Jul 1. link to original article contains verified protocol PubMed NCT00711594
Afatinib & Bevacizumab
back to top |
Regimen
Study | Years of enrollment | Evidence |
---|---|---|
Hata et al. 2018 (ABC Study) | 2014-2017 | Phase II |
Targeted therapy
- Afatinib (Gilotrif) 30 mg PO once per day
- Bevacizumab (Avastin) 15 mg/kg IV once on day 1
21-day cycles
References
- ABC Study: Hata A, Katakami N, Kaji R, Yokoyama T, Kaneda T, Tamiya M, Inoue T, Kimura H, Yano Y, Tamura D, Morita S, Negoro S; Hanshin Oncology Group F. Afatinib plus bevacizumab combination after acquired resistance to EGFR tyrosine kinase inhibitors in EGFR-mutant non-small cell lung cancer: Multicenter, single-arm, phase 2 trial (ABC Study). Cancer. 2018 Oct 1;124(19):3830-3838. Epub 2018 Sep 7. link to original article PubMed UMIN000014710
Afatinib & Cetuximab
back to top |
Regimen
Study | Years of enrollment | Evidence | Efficacy |
---|---|---|---|
Janjigian et al. 2014 (BI 1200.71) | 2010-2013 | Phase Ib | ORR: 29% |
Targeted therapy
- Afatinib (Gilotrif) 40 mg PO once per day
- Cetuximab (Erbitux) 500 mg IV once on day 1
14-day cycles
References
- BI 1200.71: Janjigian YY, Smit EF, Groen HJ, Horn L, Gettinger S, Camidge DR, Riely GJ, Wang B, Fu Y, Chand VK, Miller VA, Pao W. Dual inhibition of EGFR with afatinib and cetuximab in kinase inhibitor-resistant EGFR-mutant lung cancer with and without T790M mutations. Cancer Discov. 2014 Sep;4(9):1036-45. Epub 2014 Jul 29. link to original article link to PMC article contains verified protocol PubMed NCT01090011
Cisplatin & Pemetrexed
back to top |
Regimen
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Soria et al. 2015 (IMPRESS) | 2012-2013 | Phase 3 (C) | Cisplatin, Pemetrexed, Gefitinib | Did not meet primary endpoint of PFS |
Patients enrolled in IMPRESS were EGFR mutation positive and had progression after first-line gefitinib.
Chemotherapy
- Cisplatin (Platinol) 75 mg/m2 IV once on day 1
- Pemetrexed (Alimta) 500 mg/m2 IV once on day 1
Supportive medications
- (as described in Scagliotti et al. 2008):
- Cyanocobalamin (Vitamin B12) 1000 mcg IM every 9 weeks, first dose prior to Pemetrexed (Alimta)
- Folic acid (Folate) 1 mg PO once per day
- In Sequist et al. 2013: Patients "received Folic acid (Folate), vitamin B12, and dexamethasone, as per package recommendations for Pemetrexed (Alimta)."
21-day cycle for 4 to 6 cycles
References
- IMPRESS: Soria JC, Wu YL, Nakagawa K, Kim SW, Yang JJ, Ahn MJ, Wang J, Yang JC, Lu Y, Atagi S, Ponce S, Lee DH, Liu Y, Yoh K, Zhou JY, Shi X, Webster A, Jiang H, Mok TS. Gefitinib plus chemotherapy versus placebo plus chemotherapy in EGFR-mutation-positive non-small-cell lung cancer after progression on first-line gefitinib (IMPRESS): a phase 3 randomised trial. Lancet Oncol. 2015 Aug;16(8):990-8. Epub 2015 Jul 6. link to original article contains verified protocol PubMed NCT01544179
- Update: Mok TSK, Kim SW, Wu YL, Nakagawa K, Yang JJ, Ahn MJ, Wang J, Yang JC, Lu Y, Atagi S, Ponce S, Shi X, Rukazenkov Y, Haddad V, Thress KS, Soria JC. Gefitinib plus chemotherapy versus chemotherapy in epidermal growth factor receptor mutation-positive non-small-cell lung cancer resistant to first-line gefitinib (IMPRESS): overall survival and biomarker analyses. J Clin Oncol. 2017 Dec 20;35(36):4027-4034. Epub 2017 Oct 2. link to original article PubMed
Advanced or metastatic disease, EGFR p.T790M mutation
Carboplatin & Pemetrexed
back to top |
Regimen
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Mok et al. 2016 (AURA3) | 2014-2015 | Phase 3 (C) | Osimertinib | Inferior PFS |
Patients enrolled in AURA3 had locally advanced or metastatic NSCLC with progression after first-line EGFR TKI therapy, and were required to have presence of an EGFR p.T790M mutation.
Chemotherapy
- Carboplatin (Paraplatin) AUC 5 IV over 15 to 60 minutes once on day 1, given second
- Pemetrexed (Alimta) 500 mg/m2 IV over 10 minutes once on day 1, given first
Supportive medications
- (Ardizzoni et al. 2012 contained more details):
- Dexamethasone (Decadron) 4 mg or equivalent corticosteroid PO twice per day on the day before, the day of, and day after each dose of Pemetrexed (Alimta)
- Folic acid (Folate) 350 to 600 mcg PO once per day, starting 1 to 2 weeks before the first dose of Pemetrexed (Alimta), to be taken throughout pemetrexed therapy
- Cyanocobalamin (Vitamin B12) 1000 mcg IM once every 9 weeks, first dose 1 to 2 weeks before the first dose of Pemetrexed (Alimta), to be given throughout pemetrexed therapy
21-day cycle for 4 to 6 cycles
Subsequent treatment
- Optional pemetrexed maintenance
References
- AURA3: Mok TS, Wu YL, Ahn MJ, Garassino MC, Kim HR, Ramalingam SS, Shepherd FA, He Y, Akamatsu H, Theelen WS, Lee CK, Sebastian M, Templeton A, Mann H, Marotti M, Ghiorghiu S, Papadimitrakopoulou VA; AURA3 Investigators. Osimertinib or platinum-pemetrexed in EGFR T790M-positive lung cancer. N Engl J Med. 2017 Feb 16;376(7):629-640. Epub 2016 Dec 6. link to original article contains verified protocol link to PMC article PubMed NCT02151981
- Subgroup analysis: Wu YL, Ahn MJ, Garassino MC, Han JY, Katakami N, Kim HR, Hodge R, Kaur P, Brown AP, Ghiorghiu D, Papadimitrakopoulou VA, Mok TSK. CNS efficacy of osimertinib in patients with T790M-positive advanced non-small-cell lung cancer: data from a randomized phase III trial (AURA3). J Clin Oncol. 2018 Sep 10;36(26):2702-2709. Epub 2018 Jul 30. link to original article PubMed
- Update: Papadimitrakopoulou VA, Mok TS, Han JY, Ahn MJ, Delmonte A, Ramalingam SS, Kim SW, Shepherd FA, Laskin J, He Y, Akamatsu H, Theelen WSME, Su WC, John T, Sebastian M, Mann H, Miranda M, Laus G, Rukazenkov Y, Wu YL. Osimertinib versus platinum-pemetrexed for patients with EGFR T790M advanced NSCLC and progression on a prior EGFR-tyrosine kinase inhibitor: AURA3 overall survival analysis. Ann Oncol. 2020 Aug 27:S0923-7534(20)42155-6. Epub ahead of print. link to original article PubMed
Cisplatin & Pemetrexed
back to top |
Regimen
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Mok et al. 2016 (AURA3) | 2014-2015 | Phase 3 (C) | Osimertinib | Inferior PFS |
Patients enrolled in AURA3 had locally advanced or metastatic NSCLC with progression after first-line EGFR TKI therapy, and were required to have presence of an EGFR p.T790M mutation.
Chemotherapy
- Cisplatin (Platinol) 75 mg/m2 IV once on day 1
- Pemetrexed (Alimta) 500 mg/m2 IV once on day 1
Supportive medications
- (as described in Scagliotti et al. 2008):
- Cyanocobalamin (Vitamin B12) 1000 mcg IM every 9 weeks, first dose prior to Pemetrexed (Alimta)
- Folic acid (Folate) 1 mg PO once per day
- In Sequist et al. 2013: Patients "received Folic acid (Folate), vitamin B12, and dexamethasone, as per package recommendations for Pemetrexed (Alimta)."
21-day cycle for 4 to 6 cycles
Subsequent treatment
- Patients without disease progression could optionally proceed to pemetrexed maintenance after 4 cycles
References
- AURA3: Mok TS, Wu YL, Ahn MJ, Garassino MC, Kim HR, Ramalingam SS, Shepherd FA, He Y, Akamatsu H, Theelen WS, Lee CK, Sebastian M, Templeton A, Mann H, Marotti M, Ghiorghiu S, Papadimitrakopoulou VA; AURA3 Investigators. Osimertinib or platinum-pemetrexed in EGFR T790M-positive lung cancer. N Engl J Med. 2017 Feb 16;376(7):629-640. Epub 2016 Dec 6. link to original article contains verified protocol link to PMC article PubMed NCT02151981
- Subgroup analysis: Wu YL, Ahn MJ, Garassino MC, Han JY, Katakami N, Kim HR, Hodge R, Kaur P, Brown AP, Ghiorghiu D, Papadimitrakopoulou VA, Mok TSK. CNS efficacy of osimertinib in patients with T790M-positive advanced non-small-cell lung cancer: data from a randomized phase III trial (AURA3). J Clin Oncol. 2018 Sep 10;36(26):2702-2709. Epub 2018 Jul 30. link to original article PubMed
- Update: Papadimitrakopoulou VA, Mok TS, Han JY, Ahn MJ, Delmonte A, Ramalingam SS, Kim SW, Shepherd FA, Laskin J, He Y, Akamatsu H, Theelen WSME, Su WC, John T, Sebastian M, Mann H, Miranda M, Laus G, Rukazenkov Y, Wu YL. Osimertinib versus platinum-pemetrexed for patients with EGFR T790M advanced NSCLC and progression on a prior EGFR-tyrosine kinase inhibitor: AURA3 overall survival analysis. Ann Oncol. 2020 Aug 27:S0923-7534(20)42155-6. Epub ahead of print. link to original article PubMed
Docetaxel & Bevacizumab
back to top |
Regimen
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Nie et al. 2018 (QingdaoCH20161101) | 2015-2016 | Phase 3 (C) | Osimertinib | Inferior PFS |
Note: to our knowledge, this regimen was not tested as an experimental arm in an RCT prior to becoming a standard comparator arm. Enrolled patients had EGFR p.T790M mutations.
Chemotherapy
- Docetaxel (Taxotere) 75 mg/m2 IV once on day 1
Targeted therapy
- Bevacizumab (Avastin) 7.5 mg/kg IV once on day 1
21-day cycles
References
- QingdaoCH20161101: Nie K, Zhang Z, Zhang C, Geng C, Zhang L, Xu X, Liu S, Wang S, Zhuang X, Lan K, Ji Y. Osimertinib compared docetaxel-bevacizumab as third-line treatment in EGFR T790M mutated non-small-cell lung cancer. Lung Cancer. 2018 Jul;121:5-11. Epub 2018 Apr 17. link to original article contains protocol PubMed NCT02959749
Osimertinib monotherapy
back to top |
Regimen
FDA-recommended dose |
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Jänne et al. 2015 (AURA) | 2013-NR | Phase 1, >20 pts in this dosing cohort (RT) | ||
Goss et al. 2016 (AURA2) | 2014 | Phase II (RT) | ||
Mok et al. 2016 (AURA3) | 2014-2015 | Phase 3 (E-RT-switch-ooc) | 1. Carboplatin & Pemetrexed 2. Cisplatin & Pemetrexed |
Superior PFS Median PFS: 10.1 vs 4.4 mo (HR 0.30, 95% CI 0.23-0.41) |
Nie et al. 2018 (QingdaoCH20161101) | 2015-2016 | Phase 3 (E-switch-ooc) | Docetaxel & Bevacizumab | Superior PFS |
Patients enrolled in AURA3 had locally advanced or metastatic NSCLC with progression after first-line EGFR TKI therapy.
Biomarker eligibility criteria
- AURA3: EGFR p.T790M mutation
Targeted therapy
- Osimertinib (Tagrisso) 80 mg PO once per day
Continued indefinitely
References
- Phase 1: Jänne PA, Yang JC, Kim DW, Planchard D, Ohe Y, Ramalingam SS, Ahn MJ, Kim SW, Su WC, Horn L, Haggstrom D, Felip E, Kim JH, Frewer P, Cantarini M, Brown KH, Dickinson PA, Ghiorghiu S, Ranson M. AZD9291 in EGFR inhibitor-resistant non-small-cell lung cancer. N Engl J Med. 2015 Apr 30;372(18):1689-99. link to original article contains verified protocol PubMed NCT01802632
- AURA2: Goss G, Tsai CM, Shepherd FA, Bazhenova L, Lee JS, Chang GC, Crino L, Satouchi M, Chu Q, Hida T, Han JY, Juan O, Dunphy F, Nishio M, Kang JH, Majem M, Mann H, Cantarini M, Ghiorghiu S, Mitsudomi T. Osimertinib for pretreated EGFR Thr790Met-positive advanced non-small-cell lung cancer (AURA2): a multicentre, open-label, single-arm, phase 2 study. Lancet Oncol. 2016 Dec;17(12):1643-1652. Epub 2016 Oct 14. link to original article PubMed NCT02094261
- AURA3: Mok TS, Wu YL, Ahn MJ, Garassino MC, Kim HR, Ramalingam SS, Shepherd FA, He Y, Akamatsu H, Theelen WS, Lee CK, Sebastian M, Templeton A, Mann H, Marotti M, Ghiorghiu S, Papadimitrakopoulou VA; AURA3 Investigators. Osimertinib or platinum-pemetrexed in EGFR T790M-positive lung cancer. N Engl J Med. 2017 Feb 16;376(7):629-640. Epub 2016 Dec 6. link to original article contains verified protocol link to PMC article PubMed NCT02151981
- Subgroup analysis: Wu YL, Ahn MJ, Garassino MC, Han JY, Katakami N, Kim HR, Hodge R, Kaur P, Brown AP, Ghiorghiu D, Papadimitrakopoulou VA, Mok TSK. CNS efficacy of osimertinib in patients with T790M-positive advanced non-small-cell lung cancer: data from a randomized phase III trial (AURA3). J Clin Oncol. 2018 Sep 10;36(26):2702-2709. Epub 2018 Jul 30. link to original article PubMed
- Update: Papadimitrakopoulou VA, Mok TS, Han JY, Ahn MJ, Delmonte A, Ramalingam SS, Kim SW, Shepherd FA, Laskin J, He Y, Akamatsu H, Theelen WSME, Su WC, John T, Sebastian M, Mann H, Miranda M, Laus G, Rukazenkov Y, Wu YL. Osimertinib versus platinum-pemetrexed for patients with EGFR T790M advanced NSCLC and progression on a prior EGFR-tyrosine kinase inhibitor: AURA3 overall survival analysis. Ann Oncol. 2020 Aug 27:S0923-7534(20)42155-6. Epub ahead of print. link to original article PubMed
- QingdaoCH20161101: Nie K, Zhang Z, Zhang C, Geng C, Zhang L, Xu X, Liu S, Wang S, Zhuang X, Lan K, Ji Y. Osimertinib compared docetaxel-bevacizumab as third-line treatment in EGFR T790M mutated non-small-cell lung cancer. Lung Cancer. 2018 Jul;121:5-11. Epub 2018 Apr 17. link to original article contains protocol PubMed NCT0295974
CNS metastases, all lines of therapy
Afatinib monotherapy
back to top |
Regimen
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Sequist et al. 2013 (LUX-Lung 3) | 2009-2011 | Phase 3 (E-switch-ooc) | Cisplatin & Pemetrexed | Seems to have superior PFS1 |
Wu et al. 2014 (LUX-Lung 6) | 2010-2011 | Phase 3 (E-switch-ooc) | Cisplatin & Gemcitabine | Seems to have superior PFS1 |
1Reported CNS-specific efficacy is based on the 2016 pooled subgroup analysis.
Biomarker eligibility criteria
- Gene EGFR mutation (Leu858Arg, exon 19 deletions, or other)
Targeted therapy
- Afatinib (Gilotrif) 40 mg PO once per day, given 1 hour before eating food (LUX-Lung 2: "no food intake immediately before or after afatinib")
- In LUX-Lung 3, patients could be increased to 50 mg PO once per day if they did not experience any grade 2 or higher rash, diarrhea, mucositis, or other drug-related adverse event.
Continued indefinitely
References
- LUX-Lung 3: Sequist LV, Yang JC, Yamamoto N, O'Byrne K, Hirsh V, Mok T, Geater SL, Orlov S, Tsai CM, Boyer M, Su WC, Bennouna J, Kato T, Gorbunova V, Lee KH, Shah R, Massey D, Zazulina V, Shahidi M, Schuler M. Phase III study of afatinib or cisplatin plus pemetrexed in patients with metastatic lung adenocarcinoma with EGFR mutations. J Clin Oncol. 2013 Sep 20;31(27):3327-34. Epub 2013 Jul 1. link to original article contains verified protocol PubMed NCT00949650
- HRQoL analysis: Yang JC, Hirsh V, Schuler M, Yamamoto N, O'Byrne KJ, Mok TS, Zazulina V, Shahidi M, Lungershausen J, Massey D, Palmer M, Sequist LV. Symptom control and quality of life in LUX-Lung 3: a phase III study of afatinib or cisplatin/pemetrexed in patients with advanced lung adenocarcinoma with EGFR mutations. J Clin Oncol. 2013 Sep 20;31(27):3342-50. Epub 2013 Jul 1. link to original article contains verified protocol PubMed
- Pooled update: Yang JC, Wu YL, Schuler M, Sebastian M, Popat S, Yamamoto N, Zhou C, Hu CP, O'Byrne K, Feng J, Lu S, Huang Y, Geater SL, Lee KY, Tsai CM, Gorbunova V, Hirsh V, Bennouna J, Orlov S, Mok T, Boyer M, Su WC, Lee KH, Kato T, Massey D, Shahidi M, Zazulina V, Sequist LV. Afatinib versus cisplatin-based chemotherapy for EGFR mutation-positive lung adenocarcinoma (LUX-Lung 3 and LUX-Lung 6): analysis of overall survival data from two randomised, phase 3 trials. Lancet Oncol. 2015 Feb;16(2):141-51. link to original article PubMed
- Pooled analysis: Yang JC, Sequist LV, Geater SL, Tsai CM, Mok TS, Schuler M, Yamamoto N, Yu CJ, Ou SH, Zhou C, Massey D, Zazulina V, Wu YL. Clinical activity of afatinib in patients with advanced non-small-cell lung cancer harbouring uncommon EGFR mutations: a combined post-hoc analysis of LUX-Lung 2, LUX-Lung 3, and LUX-Lung 6. Lancet Oncol. 2015 Jul;16(7):830-8. Epub 2015 Jun 4. link to original article PubMed
- Subgroup analysis: Schuler M, Wu YL, Hirsh V, O'Byrne K, Yamamoto N, Mok T, Popat S, Sequist LV, Massey D, Zazulina V, Yang JC. First-line afatinib versus chemotherapy in patients with non-small cell lung cancer and common epidermal growth factor receptor gene mutations and brain metastases. J Thorac Oncol. 2016 Mar;11(3):380-90. link to original article PubMed
- LUX-Lung 6: Wu YL, Zhou C, Hu CP, Feng J, Lu S, Huang Y, Li W, Hou M, Shi JH, Lee KY, Xu CR, Massey D, Kim M, Shi Y, Geater SL. Afatinib versus cisplatin plus gemcitabine for first-line treatment of Asian patients with advanced non-small-cell lung cancer harbouring EGFR mutations (LUX-Lung 6): an open-label, randomised phase 3 trial. Lancet Oncol. 2014 Feb;15(2):213-22. link to original article contains verified protocol PubMed NCT01121393
- Pooled update: Yang JC, Wu YL, Schuler M, Sebastian M, Popat S, Yamamoto N, Zhou C, Hu CP, O'Byrne K, Feng J, Lu S, Huang Y, Geater SL, Lee KY, Tsai CM, Gorbunova V, Hirsh V, Bennouna J, Orlov S, Mok T, Boyer M, Su WC, Lee KH, Kato T, Massey D, Shahidi M, Zazulina V, Sequist LV. Afatinib versus cisplatin-based chemotherapy for EGFR mutation-positive lung adenocarcinoma (LUX-Lung 3 and LUX-Lung 6): analysis of overall survival data from two randomised, phase 3 trials. Lancet Oncol. 2015 Feb;16(2):141-51. link to original article PubMed
- Pooled analysis: Yang JC, Sequist LV, Geater SL, Tsai CM, Mok TS, Schuler M, Yamamoto N, Yu CJ, Ou SH, Zhou C, Massey D, Zazulina V, Wu YL. Clinical activity of afatinib in patients with advanced non-small-cell lung cancer harbouring uncommon EGFR mutations: a combined post-hoc analysis of LUX-Lung 2, LUX-Lung 3, and LUX-Lung 6. Lancet Oncol. 2015 Jul;16(7):830-8. Epub 2015 Jun 4. link to original article PubMed
- Subgroup analysis: Schuler M, Wu YL, Hirsh V, O'Byrne K, Yamamoto N, Mok T, Popat S, Sequist LV, Massey D, Zazulina V, Yang JC. First-line afatinib versus chemotherapy in patients with non-small cell lung cancer and common epidermal growth factor receptor gene mutations and brain metastases. J Thorac Oncol. 2016 Mar;11(3):380-90. link to original article PubMed
Icotinib monotherapy
back to top |
Regimen
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Yang et al. 2017 (BRAIN) | 2012-2015 | Phase 3 (E-switch-ooc) | WB-XRT | Seems to have superior intracranial PFS |
Note: this drug is only approved in China.
Biomarker eligibility criteria
- EGFR Mutation
- Clinical Trial Eligibility: EGFR Exon 19 deletion, EGFR exon 21 L858R, Uncommon EGFR mutations
Targeted therapy
- Icotinib (Conmana) 125 mg PO three times per day
Continued indefinitely
References
- BRAIN: Yang JJ, Zhou C, Huang Y, Feng J, Lu S, Song Y, Huang C, Wu G, Zhang L, Cheng Y, Hu C, Chen G, Zhang L, Liu X, Yan HH, Tan FL, Zhong W, Wu YL. Icotinib versus whole-brain irradiation in patients with EGFR-mutant non-small-cell lung cancer and multiple brain metastases (BRAIN): a multicentre, phase 3, open-label, parallel, randomised controlled trial. Lancet Respir Med. 2017 Sep;5(9):707-716. Epub 2017 Jul 19. link to original article contains protocol PubMed NCT01724801
Osimertinib monotherapy
back to top |
Regimen variant #1, 80 mg/day
FDA-recommended dose |
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Goss et al. 2018 (AURA extension) | 2013-NR | Phase II | ||
Mok et al. 2016 (AURA3) | 2014-2015 | Phase 3 (E-switch-ooc) | 1. Carboplatin & Pemetrexed 2. Cisplatin & Pemetrexed |
Seems to have superior ORR1 |
Soria et al. 2017 (FLAURA) | 2014-2016 | Phase 3 (E-switch-ic) | 1. Erlotinib 2. Gefitinib |
Seems to have superior PFS2 |
Goss et al. 2018 (AURA2) | 2014-NR | Phase II |
1Reported efficacy for AURA3 is based on the 2018 subgroup analysis.
2Reported efficacy for FLAURA is based on the 2018 subgroup analysis.
Patients enrolled in AURA3 had locally advanced or metastatic NSCLC with progression after first-line EGFR TKI therapy, and were required to have presence of an EGFR p.T790M mutation.
Biomarker eligibility criteria
Targeted therapy
- Osimertinib (Tagrisso) 80 mg PO once per day
Continued indefinitely
Regimen variant #2, 160 mg/day
Study | Years of enrollment | Evidence | Efficacy |
---|---|---|---|
Yang et al. 2019 (BLOOM) | 2015-2017 | Phase I, >20 pts | BICR- LM ORR (62%), DoR 15.2 months Investigator- LM ORR (41%), DoR 8.3 months |
Patients with leptomeningeal metastases (LMs) from EGFR-mutated (EGFRm) advanced non-small-cell lung cancer (NSCLC) whose disease had progressed on previous EGFR-TKI therapy. BICR- Blinded Independent Central Review, DoR- Duration of Response, ORR-Objective response rate
Biomarker eligibility criteria
Targeted therapy
- Osimertinib (Tagrisso) 160 mg PO once per day
Continued indefinitely
References
- AURA3: Mok TS, Wu YL, Ahn MJ, Garassino MC, Kim HR, Ramalingam SS, Shepherd FA, He Y, Akamatsu H, Theelen WS, Lee CK, Sebastian M, Templeton A, Mann H, Marotti M, Ghiorghiu S, Papadimitrakopoulou VA; AURA3 Investigators. Osimertinib or platinum-pemetrexed in EGFR T790M-positive lung cancer. N Engl J Med. 2017 Feb 16;376(7):629-640. Epub 2016 Dec 6. link to original article contains verified protocol PubMed NCT02151981
- Subgroup analysis: Wu YL, Ahn MJ, Garassino MC, Han JY, Katakami N, Kim HR, Hodge R, Kaur P, Brown AP, Ghiorghiu D, Papadimitrakopoulou VA, Mok TSK. CNS efficacy of osimertinib in patients with T790M-positive advanced non-small-cell lung cancer: data from a randomized phase III trial (AURA3). J Clin Oncol. 2018 Sep 10;36(26):2702-2709. Epub 2018 Jul 30. link to original article PubMed
- AURA extension; AURA2: Goss G, Tsai CM, Shepherd FA, Ahn MJ, Bazhenova L, Crinò L, de Marinis F, Felip E, Morabito A, Hodge R, Cantarini M, Johnson M, Mitsudomi T, Jänne PA, Yang JC. CNS response to osimertinib in patients with T790M-positive advanced NSCLC: pooled data from two phase II trials. Ann Oncol. 2018 Mar 1;29(3):687-693. link to original article PubMed NCT01802632; NCT02094261
- FLAURA: Soria JC, Ohe Y, Vansteenkiste J, Reungwetwattana T, Chewaskulyong B, Lee KH, Dechaphunkul A, Imamura F, Nogami N, Kurata T, Okamoto I, Zhou C, Cho BC, Cheng Y, Cho EK, Voon PJ, Planchard D, Su WC, Gray JE, Lee SM, Hodge R, Marotti M, Rukazenkov Y, Ramalingam SS; FLAURA Investigators. Osimertinib in untreated EGFR-mutated advanced non-small-cell lung cancer. N Engl J Med. 2018 Jan 11;378(2):113-125. Epub 2017 Nov 18. link to original article contains verified protocol PubMed NCT02296125
- Subgroup analysis: Reungwetwattana T, Nakagawa K, Cho BC, Cobo M, Cho EK, Bertolini A, Bohnet S, Zhou C, Lee KH, Nogami N, Okamoto I, Leighl N, Hodge R, McKeown A, Brown AP, Rukazenkov Y, Ramalingam SS, Vansteenkiste J. CNS response to osimertinib versus standard epidermal growth factor receptor tyrosine kinase inhibitors in patients with untreated EGFR-mutated advanced non-small-cell lung cancer. J Clin Oncol. 2018 Nov 20;36(33):3290-7. Epub 2018 Aug 28. link to original article PubMed
- BLOOM: Yang JCH, Kim SW, Kim DW, Lee JS, Cho BC, Ahn JS, Lee DH, Kim TM, Goldman JW, Natale RB, Brown AP, Collins B, Chmielecki J, Vishwanathan K, Mendoza-Naranjo A, Ahn MJ. Osimertinib in Patients With Epidermal Growth Factor Receptor Mutation-Positive Non-Small-Cell Lung Cancer and Leptomeningeal Metastases: The BLOOM Study. J Clin Oncol. 2020 Feb 20;38(6):538-547. Epub 2019 Dec 6. link to original article link to PMC article PubMed NCT02228369