Difference between revisions of "Non-small cell lung cancer, ROS1-positive"

From HemOnc.org - A Hematology Oncology Wiki
Jump to navigation Jump to search
m (Text replacement - "{| class="wikitable sortable" style="width: 100%; text-align:center;" !style="width: 25%"|Study !style="width: 25%"|Years of enrollment !style="width: 25%"|Evidence !style="width: 25%"|Efficacy" to "{| class="wikitable sortable" style="width: 80%; text-align:center;" !style="width: 25%"|Study !style="width: 25%"|Years of enrollment !style="width: 25%"|Evidence !style="width: 2...)
 
(44 intermediate revisions by 3 users not shown)
Line 1: Line 1:
−
{{#lst:Section editor transclusions|nsclc}}
+
<span id="BackToTop"></span>
 +
<div class="noprint" style="background-color:LightGray; position:fixed; bottom:2%; right:0.25%; padding-left:5px; padding-right:5px; margin: 15px; opacity:0.8; border-style: solid; border-color:DarkGray; border-width: 1px">
 +
[[#top|Back to Top]]
 +
</div>
 +
{{#lst:Editorial board transclusions|nsclc}}
 
Note: these are regimens tested in biomarker-specific populations, please see the '''[[Non-small cell lung cancer|main NSCLC page]]''' for other regimens.
 
Note: these are regimens tested in biomarker-specific populations, please see the '''[[Non-small cell lung cancer|main NSCLC page]]''' for other regimens.
 
{| class="wikitable" style="float:right; margin-right: 5px;"
 
{| class="wikitable" style="float:right; margin-right: 5px;"
Line 7: Line 11:
 
|}
 
|}
 
{{TOC limit|limit=3}}
 
{{TOC limit|limit=3}}
 +
=Guidelines=
 +
'''Given the rapid change in evidence in many areas of hematology/oncology, readers are encouraged to consider any guideline published 5+ years ago to be for historical purposes, only.'''
 +
==[https://www.asco.org/ ASCO]==
 +
*'''2022:''' Singh et al. [https://doi.org/10.1200/jco.22.00824 Therapy for Stage IV Non-Small-Cell Lung Cancer With Driver Alterations: ASCO Living Guideline] [https://www.ncbi.nlm.nih.gov/pubmed/35816666 PubMed]
 +
==[https://www.esmo.org/ ESMO]==
 +
*'''2023:''' Hendriks et al. [https://doi.org/10.1016/j.annonc.2022.12.009 Oncogene-addicted metastatic non-small-cell lung cancer: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up] [https://www.ncbi.nlm.nih.gov/pubmed/36872130 PubMed]
 +
==NCCN==
 +
*''NCCN does not currently have guidelines at this granular level; please see [https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1450 NCCN Guidelines - Non-Small Cell Lung Cancer].''
 +
 
=Advanced or metastatic disease, ROS1 inhibitor-naive=
 
=Advanced or metastatic disease, ROS1 inhibitor-naive=
−
 
 
==Ceritinib monotherapy {{#subobject:fe3892|Regimen=1}}==
 
==Ceritinib monotherapy {{#subobject:fe3892|Regimen=1}}==
−
{| class="wikitable" style="float:right; margin-left: 5px;"
+
<div class="toccolours" style="background-color:#eeeeee">
−
|-
 
−
|[[#top|back to top]]
 
−
|}
 
 
===Regimen {{#subobject:47c6e4|Variant=1}}===
 
===Regimen {{#subobject:47c6e4|Variant=1}}===
−
{| class="wikitable" style="width: 60%; text-align:center;"  
+
{| class="wikitable sortable" style="width: 80%; text-align:center;"  
−
!style="width: 33%"|Study
+
!style="width: 25%"|Study
−
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
+
!style="width: 25%"|Dates of enrollment
−
!style="width: 33%"|[[Levels_of_Evidence#Efficacy|Efficacy]]
+
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
 +
!style="width: 25%"|[[Levels_of_Evidence#Efficacy|Efficacy]]
 
|-
 
|-
 
|[https://doi.org/10.1200/JCO.2016.71.3701 Lim et al. 2017]
 
|[https://doi.org/10.1200/JCO.2016.71.3701 Lim et al. 2017]
 +
|2013-06-07 to 2016-02-01
 
| style="background-color:#91cf61" |Phase 2
 
| style="background-color:#91cf61" |Phase 2
 
| style="background-color:#bfd3e6" |ORR: 67% (95% CI, 48-81)
 
| style="background-color:#bfd3e6" |ORR: 67% (95% CI, 48-81)
 
|-
 
|-
 
|}
 
|}
 +
<div class="toccolours" style="background-color:#b3e2cd">
 
====Targeted therapy====
 
====Targeted therapy====
−
*[[Ceritinib (Zykadia)]] 750 mg PO once per day on an empty stomach
+
*[[Ceritinib (Zykadia)]] 750 mg PO once per day on days 1 to 28, taken on an empty stomach
−
 
 
 
'''28-day cycles'''
 
'''28-day cycles'''
−
 
+
</div></div>
 
===References===
 
===References===
−
# Lim SM, Kim HR, Lee JS, Lee KH, Lee YG, Min YJ, Cho EK, Lee SS, Kim BS, Choi MY, Shim HS, Chung JH, La Choi Y, Lee MJ, Kim M, Kim JH, Ali SM, Ahn MJ, Cho BC. Open-label, multicenter, phase II study of ceritinib in patients with non-small-cell lung cancer harboring ROS1 rearrangement. J Clin Oncol. 2017 Aug 10;35(23):2613-2618. Epub 2017 May 18. [https://doi.org/10.1200/JCO.2016.71.3701 link to original article] '''contains verified protocol''' [https://pubmed.ncbi.nlm.nih.gov/28520527 PubMed]
+
# Lim SM, Kim HR, Lee JS, Lee KH, Lee YG, Min YJ, Cho EK, Lee SS, Kim BS, Choi MY, Shim HS, Chung JH, La Choi Y, Lee MJ, Kim M, Kim JH, Ali SM, Ahn MJ, Cho BC. Open-label, multicenter, phase II study of ceritinib in patients with non-small-cell lung cancer harboring ROS1 rearrangement. J Clin Oncol. 2017 Aug 10;35(23):2613-2618. Epub 2017 May 18. [https://doi.org/10.1200/JCO.2016.71.3701 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/28520527/ PubMed] [https://clinicaltrials.gov/study/NCT01964157 NCT01964157]
  
 
==Crizotinib monotherapy {{#subobject:be5391|Regimen=1}}==
 
==Crizotinib monotherapy {{#subobject:be5391|Regimen=1}}==
−
{| class="wikitable" style="float:right; margin-left: 5px;"
+
<div class="toccolours" style="background-color:#eeeeee">
−
|-
 
−
|[[#top|back to top]]
 
−
|}
 
 
===Regimen variant #1, standard-dose {{#subobject:e9c195|Variant=1}}===
 
===Regimen variant #1, standard-dose {{#subobject:e9c195|Variant=1}}===
 
{| class="wikitable" style="color:white; background-color:#404040"
 
{| class="wikitable" style="color:white; background-color:#404040"
Line 45: Line 53:
 
{| class="wikitable sortable" style="width: 80%; text-align:center;"  
 
{| class="wikitable sortable" style="width: 80%; text-align:center;"  
 
!style="width: 25%"|Study
 
!style="width: 25%"|Study
−
!style="width: 25%"|Years of enrollment
+
!style="width: 25%"|Dates of enrollment
 
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
!style="width: 25%"|[[Levels_of_Evidence#Efficacy|Efficacy]]
 
!style="width: 25%"|[[Levels_of_Evidence#Efficacy|Efficacy]]
 
|-
 
|-
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4264527/ Shaw et al. 2014 (PROFILE 1001)]
+
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4264527/ Shaw et al. 2014 (PROFILE 1001 ROS1)]
 +
<!-- {| class="wikitable" style="margin:auto; color:white; background-color:#1B4F26"
 +
|'''[https://www.esmo.org/guidelines/esmo-mcbs/esmo-mcbs-scorecards/scorecard-129-1 <span style="color:white;">ESMO-MCBS (3)</span>]'''
 +
|-
 +
|} -->
 
|2010-2013
 
|2010-2013
−
| style="background-color:#91cf61" |Non-randomized (RT)
+
| style="background-color:#91cf61" |Phase 1 (RT)
 
|style="background-color:#bfd3e6"|ORR: 72% (95% CI, 58-84)
 
|style="background-color:#bfd3e6"|ORR: 72% (95% CI, 58-84)
 
|-
 
|-
 
|}
 
|}
−
''Note: this was an expansion cohort of a phase I study.''
+
''Note: this was an expansion cohort of a phase 1 study.''
 +
<div class="toccolours" style="background-color:#b3e2cd">
 
====Targeted therapy====
 
====Targeted therapy====
−
*[[Crizotinib (Xalkori)]] 250 mg PO twice per day
+
*[[Crizotinib (Xalkori)]] 250 mg PO twice per day on days 1 to 28
−
 
 
 
'''28-day cycles'''
 
'''28-day cycles'''
−
 
+
</div></div><br>
 +
<div class="toccolours" style="background-color:#eeeeee">
 
===Regimen variant #2, 200 mg twice per day {{#subobject:c56a8e|Variant=1}}===
 
===Regimen variant #2, 200 mg twice per day {{#subobject:c56a8e|Variant=1}}===
 
{| class="wikitable" style="color:white; background-color:#404040"
 
{| class="wikitable" style="color:white; background-color:#404040"
Line 67: Line 80:
 
|}
 
|}
 
''Note: this is the FDA-recommended dosing for "moderate" hepatic impairment.''
 
''Note: this is the FDA-recommended dosing for "moderate" hepatic impairment.''
 +
<div class="toccolours" style="background-color:#b3e2cd">
 
====Targeted therapy====
 
====Targeted therapy====
 
*[[Crizotinib (Xalkori)]] 200 mg PO twice per day
 
*[[Crizotinib (Xalkori)]] 200 mg PO twice per day
−
 
 
'''Continued indefinitely'''
 
'''Continued indefinitely'''
−
 
+
</div></div><br>
 +
<div class="toccolours" style="background-color:#eeeeee">
 
===Regimen variant #3, 250 mg/day {{#subobject:d7fdf0|Variant=1}}===
 
===Regimen variant #3, 250 mg/day {{#subobject:d7fdf0|Variant=1}}===
 
{| class="wikitable" style="color:white; background-color:#404040"
 
{| class="wikitable" style="color:white; background-color:#404040"
Line 78: Line 92:
 
|}
 
|}
 
''Note: this is the FDA-recommended dosing for "severe" hepatic or renal impairment.''
 
''Note: this is the FDA-recommended dosing for "severe" hepatic or renal impairment.''
 +
<div class="toccolours" style="background-color:#b3e2cd">
 
====Targeted therapy====
 
====Targeted therapy====
 
*[[Crizotinib (Xalkori)]] 250 mg PO once per day
 
*[[Crizotinib (Xalkori)]] 250 mg PO once per day
−
 
 
'''Continued indefinitely'''
 
'''Continued indefinitely'''
−
 
+
</div></div>
 
===References===
 
===References===
−
# '''PROFILE 1001:''' Shaw AT, Ou SH, Bang YJ, Camidge DR, Solomon BJ, Salgia R, Riely GJ, Varella-Garcia M, Shapiro GI, Costa DB, Doebele RC, Le LP, Zheng Z, Tan W, Stephenson P, Shreeve SM, Tye LM, Christensen JG, Wilner KD, Clark JW, Iafrate AJ. Crizotinib in ROS1-rearranged non-small-cell lung cancer. N Engl J Med. 2014 Nov 20;371(21):1963-71. Epub 2014 Sep 27. [https://www.nejm.org/doi/full/10.1056/NEJMoa1406766 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4264527/ link to PMC article] '''contains verified protocol''' [https://pubmed.ncbi.nlm.nih.gov/25264305 PubMed]
+
# '''PROFILE 1001 ROS1:''' Shaw AT, Ou SH, Bang YJ, Camidge DR, Solomon BJ, Salgia R, Riely GJ, Varella-Garcia M, Shapiro GI, Costa DB, Doebele RC, Le LP, Zheng Z, Tan W, Stephenson P, Shreeve SM, Tye LM, Christensen JG, Wilner KD, Clark JW, Iafrate AJ. Crizotinib in ROS1-rearranged non-small-cell lung cancer. N Engl J Med. 2014 Nov 20;371(21):1963-71. Epub 2014 Sep 27. [https://doi.org/10.1056/NEJMoa1406766 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4264527/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/25264305/ PubMed] [https://clinicaltrials.gov/study/NCT00585195 NCT00585195]
 +
##'''Update:''' Shaw AT, Riely GJ, Bang YJ, Kim DW, Camidge DR, Solomon BJ, Varella-Garcia M, Iafrate AJ, Shapiro GI, Usari T, Wang SC, Wilner KD, Clark JW, Ou SI. Crizotinib in ROS1-rearranged advanced non-small-cell lung cancer (NSCLC): updated results, including overall survival, from PROFILE 1001. Ann Oncol. 2019 Jul 1;30(7):1121-1126. [https://doi.org/10.1093/annonc/mdz131 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc6637370/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/30980071/ PubMed]
  
 
==Entrectinib monotherapy {{#subobject:bcja91|Regimen=1}}==
 
==Entrectinib monotherapy {{#subobject:bcja91|Regimen=1}}==
−
{| class="wikitable" style="float:right; margin-left: 5px;"
+
<div class="toccolours" style="background-color:#eeeeee">
−
|-
 
−
|[[#top|back to top]]
 
−
|}
 
 
===Regimen {{#subobject:ehac84|Variant=1}}===
 
===Regimen {{#subobject:ehac84|Variant=1}}===
 
{| class="wikitable" style="color:white; background-color:#404040"
 
{| class="wikitable" style="color:white; background-color:#404040"
Line 98: Line 110:
 
{| class="wikitable" style="width: 60%; text-align:center;"  
 
{| class="wikitable" style="width: 60%; text-align:center;"  
 
!style="width: 33%"|Study
 
!style="width: 33%"|Study
−
!style="width: 33%"|Years of enrollment
+
!style="width: 33%"|Dates of enrollment
 
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
|-
 
|-
 
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5380583/ Drilon et al. 2017 (ALKA-372-001)]
 
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5380583/ Drilon et al. 2017 (ALKA-372-001)]
−
|2012-2016
+
<!-- {| class="wikitable" style="margin:auto; color:white; background-color:#1B4F26"
−
| style="background-color:#91cf61" |Phase I
+
|'''[https://www.esmo.org/guidelines/esmo-mcbs/esmo-mcbs-scorecards/scorecard-210-1 <span style="color:white;">ESMO-MCBS (3)</span>]'''
 +
|-
 +
|} -->
 +
|2012-2018
 +
| style="background-color:#91cf61" |Phase 1 (RT)
 
|-
 
|-
 
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5380583/ Drilon et al. 2017 (STARTRK-1)]
 
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5380583/ Drilon et al. 2017 (STARTRK-1)]
−
|2012-2016
+
<!-- {| class="wikitable" style="margin:auto; color:white; background-color:#1B4F26"
−
| style="background-color:#91cf61" |Phase I (RT)
+
|'''[https://www.esmo.org/guidelines/esmo-mcbs/esmo-mcbs-scorecards/scorecard-210-1 <span style="color:white;">ESMO-MCBS (3)</span>]'''
 +
|-
 +
|} -->
 +
|2012-2018
 +
| style="background-color:#91cf61" |Phase 1 (RT)
 
|-
 
|-
 
|}
 
|}
 
''Note: this is the MTD used in the phase 2 portion; it is also the FDA-recommended dose for adults.''
 
''Note: this is the MTD used in the phase 2 portion; it is also the FDA-recommended dose for adults.''
 +
<div class="toccolours" style="background-color:#b3e2cd">
 +
====Targeted therapy====
 +
*[[Entrectinib (Rozlytrek)]] 600 mg PO once per day on days 1 to 28
 +
'''28-day cycles'''
 +
</div></div>
 +
===References===
 +
# '''ALKA-372-001:''' Drilon A, Siena S, Ou SI, Patel M, Ahn MJ, Lee J, Bauer TM, Farago AF, Wheler JJ, Liu SV, Doebele R, Giannetta L, Cerea G, Marrapese G, Schirru M, Amatu A, Bencardino K, Palmeri L, Sartore-Bianchi A, Vanzulli A, Cresta S, Damian S, Duca M, Ardini E, Li G, Christiansen J, Kowalski K, Johnson AD, Patel R, Luo D, Chow-Maneval E, Hornby Z, Multani PS, Shaw AT, De Braud FG. Safety and antitumor activity of the multitargeted pan-TRK, ROS1, and ALK inhibitor entrectinib: combined results from two phase I trials (ALKA-372-001 and STARTRK-1). Cancer Discov. 2017 Apr;7(4):400-409. Epub 2017 Feb 9. [https://doi.org/10.1158/2159-8290.CD-16-1237 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5380583/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/28183697/ PubMed] EudraCT 2012-000148-88
 +
##'''Pooled update:''' Drilon A, Siena S, Dziadziuszko R, Barlesi F, Krebs MG, Shaw AT, de Braud F, Rolfo C, Ahn MJ, Wolf J, Seto T, Cho BC, Patel MR, Chiu CH, John T, Goto K, Karapetis CS, Arkenau HT, Kim SW, Ohe Y, Li YC, Chae YK, Chung CH, Otterson GA, Murakami H, Lin CC, Tan DSW, Prenen H, Riehl T, Chow-Maneval E, Simmons B, Cui N, Johnson A, Eng S, Wilson TR, Doebele RC; trial investigators. Entrectinib in ROS1 fusion-positive non-small-cell lung cancer: integrated analysis of three phase 1-2 trials. Lancet Oncol. 2020 Feb;21(2):261-270. Epub 2019 Dec 11. Erratum in: Lancet Oncol. 2020 Feb;21(2):e70. Erratum in: Lancet Oncol. 2020 Jul;21(7):e341. [https://doi.org/10.1016/s1470-2045(19)30690-4 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc7811790/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/31838015/ PubMed]
 +
##'''Pooled update:''' Dziadziuszko R, Krebs MG, De Braud F, Siena S, Drilon A, Doebele RC, Patel MR, Cho BC, Liu SV, Ahn MJ, Chiu CH, Farago AF, Lin CC, Karapetis CS, Li YC, Day BM, Chen D, Wilson TR, Barlesi F. Updated Integrated Analysis of the Efficacy and Safety of Entrectinib in Locally Advanced or Metastatic ROS1 Fusion-Positive Non-Small-Cell Lung Cancer. J Clin Oncol. 2021 Apr 10;39(11):1253-1263. Epub 2021 Mar 1. [https://doi.org/10.1200/jco.20.03025 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc8078299/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/33646820/ PubMed]
 +
# '''STARTRK-1:''' Drilon A, Siena S, Ou SI, Patel M, Ahn MJ, Lee J, Bauer TM, Farago AF, Wheler JJ, Liu SV, Doebele R, Giannetta L, Cerea G, Marrapese G, Schirru M, Amatu A, Bencardino K, Palmeri L, Sartore-Bianchi A, Vanzulli A, Cresta S, Damian S, Duca M, Ardini E, Li G, Christiansen J, Kowalski K, Johnson AD, Patel R, Luo D, Chow-Maneval E, Hornby Z, Multani PS, Shaw AT, De Braud FG. Safety and antitumor activity of the multitargeted pan-TRK, ROS1, and ALK inhibitor entrectinib: combined results from two phase I trials (ALKA-372-001 and STARTRK-1). Cancer Discov. 2017 Apr;7(4):400-409. Epub 2017 Feb 9. [https://doi.org/10.1158/2159-8290.CD-16-1237 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5380583/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/28183697/ PubMed] [https://clinicaltrials.gov/study/NCT02097810 NCT02097810]
 +
##'''Pooled update:''' Drilon A, Siena S, Dziadziuszko R, Barlesi F, Krebs MG, Shaw AT, de Braud F, Rolfo C, Ahn MJ, Wolf J, Seto T, Cho BC, Patel MR, Chiu CH, John T, Goto K, Karapetis CS, Arkenau HT, Kim SW, Ohe Y, Li YC, Chae YK, Chung CH, Otterson GA, Murakami H, Lin CC, Tan DSW, Prenen H, Riehl T, Chow-Maneval E, Simmons B, Cui N, Johnson A, Eng S, Wilson TR, Doebele RC; trial investigators. Entrectinib in ROS1 fusion-positive non-small-cell lung cancer: integrated analysis of three phase 1-2 trials. Lancet Oncol. 2020 Feb;21(2):261-270. Epub 2019 Dec 11. Erratum in: Lancet Oncol. 2020 Feb;21(2):e70. Erratum in: Lancet Oncol. 2020 Jul;21(7):e341. [https://doi.org/10.1016/s1470-2045(19)30690-4 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc7811790/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/31838015/ PubMed]
 +
##'''Pooled update:''' Dziadziuszko R, Krebs MG, De Braud F, Siena S, Drilon A, Doebele RC, Patel MR, Cho BC, Liu SV, Ahn MJ, Chiu CH, Farago AF, Lin CC, Karapetis CS, Li YC, Day BM, Chen D, Wilson TR, Barlesi F. Updated Integrated Analysis of the Efficacy and Safety of Entrectinib in Locally Advanced or Metastatic ROS1 Fusion-Positive Non-Small-Cell Lung Cancer. J Clin Oncol. 2021 Apr 10;39(11):1253-1263. Epub 2021 Mar 1. [https://doi.org/10.1200/jco.20.03025 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc8078299/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/33646820/ PubMed]
 +
==Repotrectinib monotherapy {{#subobject:bi05c1|Regimen=1}}==
 +
<div class="toccolours" style="background-color:#eeeeee">
 +
===Regimen {{#subobject:755c84|Variant=1}}===
 +
{| class="wikitable" style="color:white; background-color:#404040"
 +
|<small>'''FDA-recommended dose'''</small>
 +
|-
 +
|}
 +
{| class="wikitable" style="width: 60%; text-align:center;"
 +
!style="width: 33%"|Study
 +
!style="width: 33%"|Dates of enrollment
 +
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 +
|-
 +
|[https://doi.org/10.1056/nejmoa2302299 Drilon et al. 2024 (TRIDENT-1)]
 +
|2017-02-27 to 2022-12-19
 +
| style="background-color:#91cf61" |Phase 1/2 (RT)
 +
|-
 +
|}
 +
<div class="toccolours" style="background-color:#b3e2cd">
 
====Targeted therapy====
 
====Targeted therapy====
−
*[[Entrectinib (Rozlytrek)]] 600 mg PO once per day
+
*[[Repotrectinib (Augtyro)]] as follows:
 +
**Cycle 1: 160 mg PO once per day on days 1 to 14, then 160 mg PO twice per day on days 15 to 28
 +
**Cycle 2 onwards: 160 mg PO twice per day on days 1 to 28
 +
'''28-day cycles'''
 +
</div></div>
 +
===References===
 +
#'''TRIDENT-1:''' Drilon A, Camidge DR, Lin JJ, Kim SW, Solomon BJ, Dziadziuszko R, Besse B, Goto K, de Langen AJ, Wolf J, Lee KH, Popat S, Springfeld C, Nagasaka M, Felip E, Yang N, Velcheti V, Lu S, Kao S, Dooms C, Krebs MG, Yao W, Beg MS, Hu X, Moro-Sibilot D, Cheema P, Stopatschinskaja S, Mehta M, Trone D, Graber A, Sims G, Yuan Y, Cho BC; TRIDENT-1 Investigators. Repotrectinib in ROS1 Fusion-Positive Non-Small-Cell Lung Cancer. N Engl J Med. 2024 Jan 11;390(2):118-131. [https://doi.org/10.1056/nejmoa2302299 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/38197815/ PubMed] [https://clinicaltrials.gov/study/NCT03093116 NCT03093116]
  
−
'''Continued indefinitely'''
+
=Advanced or metastatic disease, ROS1 inhibitor-exposed=
 +
==Lorlatinib monotherapy {{#subobject:ea894c|Regimen=1}}==
 +
<div class="toccolours" style="background-color:#eeeeee">
 +
===Regimen {{#subobject:9134b2|Variant=1}}===
 +
{| class="wikitable" style="width: 60%; text-align:center;"
 +
!style="width: 33%"|Study
 +
!style="width: 33%"|Dates of enrollment
 +
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 +
|-
 +
|[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc5777233/ Shaw et al. 2017 (B7461001)]
 +
|2014-2016
 +
| style="background-color:#91cf61" |Phase 1/2
 +
|-
 +
|}
 +
<div class="toccolours" style="background-color:#b3e2cd">
 +
====Targeted therapy====
 +
*[[Lorlatinib (Lorbrena)]] 100 mg PO once per day on days 1 to 28
 +
'''28-day cycles'''
 +
</div></div>
  
 
===References===
 
===References===
−
# '''Phase 1:''' Drilon A, Siena S, Ou SI, Patel M, Ahn MJ, Lee J, Bauer TM, Farago AF, Wheler JJ, Liu SV, Doebele R, Giannetta L, Cerea G, Marrapese G, Schirru M, Amatu A, Bencardino K, Palmeri L, Sartore-Bianchi A, Vanzulli A, Cresta S, Damian S, Duca M, Ardini E, Li G, Christiansen J, Kowalski K, Johnson AD, Patel R, Luo D, Chow-Maneval E, Hornby Z, Multani PS, Shaw AT, De Braud FG. Safety and antitumor activity of the multitargeted pan-TRK, ROS1, and ALK inhibitor entrectinib: combined results from two phase I trials (ALKA-372-001 and STARTRK-1). Cancer Discov. 2017 Apr;7(4):400-409. Epub 2017 Feb 9. [http://cancerdiscovery.aacrjournals.org/content/7/4/400.long link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5380583/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/28183697 PubMed]
+
# '''B7461001:''' Shaw AT, Felip E, Bauer TM, Besse B, Navarro A, Postel-Vinay S, Gainor JF, Johnson M, Dietrich J, James LP, Clancy JS, Chen J, Martini JF, Abbattista A, Solomon BJ. Lorlatinib in non-small-cell lung cancer with ALK or ROS1 rearrangement: an international, multicentre, open-label, single-arm first-in-man phase 1 trial. Lancet Oncol. 2017 Dec;18(12):1590-1599. Epub 2017 Oct 23. [https://doi.org/10.1016/S1470-2045(17)30680-0 link to original article] '''contains dosing details in abstract''' [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc5777233/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/29074098/ PubMed] [https://clinicaltrials.gov/study/NCT01970865 NCT01970865]
 +
##'''Update:''' Shaw AT, Solomon BJ, Chiari R, Riely GJ, Besse B, Soo RA, Kao S, Lin CC, Bauer TM, Clancy JS, Thurm H, Martini JF, Peltz G, Abbattista A, Li S, Ou SI. Lorlatinib in advanced ROS1-positive non-small-cell lung cancer: a multicentre, open-label, single-arm, phase 1-2 trial. Lancet Oncol. 2019 Dec;20(12):1691-1701. Epub 2019 Oct 25. [https://doi.org/10.1016/s1470-2045(19)30655-2 link to original article] [https://pubmed.ncbi.nlm.nih.gov/31669155/ PubMed]
  
−
=Advanced or metastatic disease, ROS1 inhibitor-exposed=
+
==Repotrectinib monotherapy {{#subobject:br05c1|Regimen=1}}==
−
==Lorlatinib monotherapy {{#subobject:ea894c|Regimen=1}}==
+
<div class="toccolours" style="background-color:#eeeeee">
−
{| class="wikitable" style="float:right; margin-left: 5px;"
+
===Regimen {{#subobject:rr5c84|Variant=1}}===
 +
{| class="wikitable" style="color:white; background-color:#404040"
 +
|<small>'''FDA-recommended dose'''</small>
 
|-
 
|-
−
|[[#top|back to top]]
 
 
|}
 
|}
−
===Regimen {{#subobject:9134b2|Variant=1}}===
+
{| class="wikitable" style="width: 60%; text-align:center;"  
−
{| class="wikitable" style="width: 40%; text-align:center;"  
+
!style="width: 33%"|Study
−
!style="width: 25%"|Study
+
!style="width: 33%"|Dates of enrollment
−
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
|-
 
|-
−
|[https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(17)30680-0/fulltext Shaw et al. 2017 (B7461001)]
+
|[https://doi.org/10.1056/nejmoa2302299 Drilon et al. 2024 (TRIDENT-1)]
−
| style="background-color:#ffffbe" |Phase I, <20 pts in this subgroup
+
|2017-02-27 to 2022-12-19
 +
| style="background-color:#91cf61" |Phase 1/2 (RT)
 
|-
 
|-
 
|}
 
|}
 +
<div class="toccolours" style="background-color:#b3e2cd">
 
====Targeted therapy====
 
====Targeted therapy====
−
*[[Lorlatinib (Lorbrena)]] 100 mg PO once per day
+
*[[Repotrectinib (Augtyro)]] as follows:
−
 
+
**Cycle 1: 160 mg PO once per day on days 1 to 14, then 160 mg PO twice per day on days 15 to 28
−
'''Continued indefinitely'''
+
**Cycle 2 onwards: 160 mg PO twice per day on days 1 to 28
 +
'''28-day cycles'''
 +
</div></div>
 
===References===
 
===References===
−
# '''Phase 1:''' Shaw AT, Felip E, Bauer TM, Besse B, Navarro A, Postel-Vinay S, Gainor JF, Johnson M, Dietrich J, James LP, Clancy JS, Chen J, Martini JF, Abbattista A, Solomon BJ. Lorlatinib in non-small-cell lung cancer with ALK or ROS1 rearrangement: an international, multicentre, open-label, single-arm first-in-man phase 1 trial. Lancet Oncol. 2017 Dec;18(12):1590-1599. Epub 2017 Oct 23. [https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(17)30680-0/fulltext link to original article] '''contains protocol''' [https://pubmed.ncbi.nlm.nih.gov/29074098 PubMed]
+
#'''TRIDENT-1:''' Drilon A, Camidge DR, Lin JJ, Kim SW, Solomon BJ, Dziadziuszko R, Besse B, Goto K, de Langen AJ, Wolf J, Lee KH, Popat S, Springfeld C, Nagasaka M, Felip E, Yang N, Velcheti V, Lu S, Kao S, Dooms C, Krebs MG, Yao W, Beg MS, Hu X, Moro-Sibilot D, Cheema P, Stopatschinskaja S, Mehta M, Trone D, Graber A, Sims G, Yuan Y, Cho BC; TRIDENT-1 Investigators. Repotrectinib in ROS1 Fusion-Positive Non-Small-Cell Lung Cancer. N Engl J Med. 2024 Jan 11;390(2):118-131. [https://doi.org/10.1056/nejmoa2302299 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/38197815/ PubMed] [https://clinicaltrials.gov/study/NCT03093116 NCT03093116]
  
 
=Additional resources=
 
=Additional resources=
 
*[https://ros1cancer.com/ The ROS1ders]
 
*[https://ros1cancer.com/ The ROS1ders]
−
 
−
=Investigational agents=
 
−
''Drugs with some degree of promising activity in clinical trials.''
 
−
 
 
[[Category:Non-small cell lung cancer regimens]]
 
[[Category:Non-small cell lung cancer regimens]]
 
[[Category:Biomarker-specific pages]]
 
[[Category:Biomarker-specific pages]]
 
[[Category:Non-small cell lung cancers]]
 
[[Category:Non-small cell lung cancers]]

Latest revision as of 19:47, 2 July 2024

Back to Top

Page editor Section editor
Singhi Eric.jpeg
 Eric K. Singhi, MD
MD Anderson Cancer Center
Houston, TX, USA
LinkedIn
Amit Kulkarni.jpg
 Amit Kulkarni, MBBS
University of Minnesota
Minneapolis, MN, USA
LinkedIn

Note: these are regimens tested in biomarker-specific populations, please see the main NSCLC page for other regimens.

6 regimens on this page
8 variants on this page


Guidelines

Given the rapid change in evidence in many areas of hematology/oncology, readers are encouraged to consider any guideline published 5+ years ago to be for historical purposes, only.

ASCO

ESMO

NCCN

Advanced or metastatic disease, ROS1 inhibitor-naive

Ceritinib monotherapy

Regimen

Study Dates of enrollment Evidence Efficacy
Lim et al. 2017 2013-06-07 to 2016-02-01 Phase 2 ORR: 67% (95% CI, 48-81)

Targeted therapy

28-day cycles

References

  1. Lim SM, Kim HR, Lee JS, Lee KH, Lee YG, Min YJ, Cho EK, Lee SS, Kim BS, Choi MY, Shim HS, Chung JH, La Choi Y, Lee MJ, Kim M, Kim JH, Ali SM, Ahn MJ, Cho BC. Open-label, multicenter, phase II study of ceritinib in patients with non-small-cell lung cancer harboring ROS1 rearrangement. J Clin Oncol. 2017 Aug 10;35(23):2613-2618. Epub 2017 May 18. link to original article contains dosing details in manuscript PubMed NCT01964157

Crizotinib monotherapy

Regimen variant #1, standard-dose

FDA-recommended dose
Study Dates of enrollment Evidence Efficacy
Shaw et al. 2014 (PROFILE 1001 ROS1) 2010-2013 Phase 1 (RT) ORR: 72% (95% CI, 58-84)

Note: this was an expansion cohort of a phase 1 study.

Targeted therapy

28-day cycles


Regimen variant #2, 200 mg twice per day

FDA-recommended dose

Note: this is the FDA-recommended dosing for "moderate" hepatic impairment.

Targeted therapy

Continued indefinitely


Regimen variant #3, 250 mg/day

FDA-recommended dose

Note: this is the FDA-recommended dosing for "severe" hepatic or renal impairment.

Targeted therapy

Continued indefinitely

References

  1. PROFILE 1001 ROS1: Shaw AT, Ou SH, Bang YJ, Camidge DR, Solomon BJ, Salgia R, Riely GJ, Varella-Garcia M, Shapiro GI, Costa DB, Doebele RC, Le LP, Zheng Z, Tan W, Stephenson P, Shreeve SM, Tye LM, Christensen JG, Wilner KD, Clark JW, Iafrate AJ. Crizotinib in ROS1-rearranged non-small-cell lung cancer. N Engl J Med. 2014 Nov 20;371(21):1963-71. Epub 2014 Sep 27. link to original article link to PMC article contains dosing details in manuscript PubMed NCT00585195
    1. Update: Shaw AT, Riely GJ, Bang YJ, Kim DW, Camidge DR, Solomon BJ, Varella-Garcia M, Iafrate AJ, Shapiro GI, Usari T, Wang SC, Wilner KD, Clark JW, Ou SI. Crizotinib in ROS1-rearranged advanced non-small-cell lung cancer (NSCLC): updated results, including overall survival, from PROFILE 1001. Ann Oncol. 2019 Jul 1;30(7):1121-1126. link to original article link to PMC article PubMed

Entrectinib monotherapy

Regimen

FDA-recommended dose
Study Dates of enrollment Evidence
Drilon et al. 2017 (ALKA-372-001) 2012-2018 Phase 1 (RT)
Drilon et al. 2017 (STARTRK-1) 2012-2018 Phase 1 (RT)

Note: this is the MTD used in the phase 2 portion; it is also the FDA-recommended dose for adults.

Targeted therapy

28-day cycles

References

  1. ALKA-372-001: Drilon A, Siena S, Ou SI, Patel M, Ahn MJ, Lee J, Bauer TM, Farago AF, Wheler JJ, Liu SV, Doebele R, Giannetta L, Cerea G, Marrapese G, Schirru M, Amatu A, Bencardino K, Palmeri L, Sartore-Bianchi A, Vanzulli A, Cresta S, Damian S, Duca M, Ardini E, Li G, Christiansen J, Kowalski K, Johnson AD, Patel R, Luo D, Chow-Maneval E, Hornby Z, Multani PS, Shaw AT, De Braud FG. Safety and antitumor activity of the multitargeted pan-TRK, ROS1, and ALK inhibitor entrectinib: combined results from two phase I trials (ALKA-372-001 and STARTRK-1). Cancer Discov. 2017 Apr;7(4):400-409. Epub 2017 Feb 9. link to original article link to PMC article contains dosing details in manuscript PubMed EudraCT 2012-000148-88
    1. Pooled update: Drilon A, Siena S, Dziadziuszko R, Barlesi F, Krebs MG, Shaw AT, de Braud F, Rolfo C, Ahn MJ, Wolf J, Seto T, Cho BC, Patel MR, Chiu CH, John T, Goto K, Karapetis CS, Arkenau HT, Kim SW, Ohe Y, Li YC, Chae YK, Chung CH, Otterson GA, Murakami H, Lin CC, Tan DSW, Prenen H, Riehl T, Chow-Maneval E, Simmons B, Cui N, Johnson A, Eng S, Wilson TR, Doebele RC; trial investigators. Entrectinib in ROS1 fusion-positive non-small-cell lung cancer: integrated analysis of three phase 1-2 trials. Lancet Oncol. 2020 Feb;21(2):261-270. Epub 2019 Dec 11. Erratum in: Lancet Oncol. 2020 Feb;21(2):e70. Erratum in: Lancet Oncol. 2020 Jul;21(7):e341. link to original article link to PMC article PubMed
    2. Pooled update: Dziadziuszko R, Krebs MG, De Braud F, Siena S, Drilon A, Doebele RC, Patel MR, Cho BC, Liu SV, Ahn MJ, Chiu CH, Farago AF, Lin CC, Karapetis CS, Li YC, Day BM, Chen D, Wilson TR, Barlesi F. Updated Integrated Analysis of the Efficacy and Safety of Entrectinib in Locally Advanced or Metastatic ROS1 Fusion-Positive Non-Small-Cell Lung Cancer. J Clin Oncol. 2021 Apr 10;39(11):1253-1263. Epub 2021 Mar 1. link to original article link to PMC article PubMed
  2. STARTRK-1: Drilon A, Siena S, Ou SI, Patel M, Ahn MJ, Lee J, Bauer TM, Farago AF, Wheler JJ, Liu SV, Doebele R, Giannetta L, Cerea G, Marrapese G, Schirru M, Amatu A, Bencardino K, Palmeri L, Sartore-Bianchi A, Vanzulli A, Cresta S, Damian S, Duca M, Ardini E, Li G, Christiansen J, Kowalski K, Johnson AD, Patel R, Luo D, Chow-Maneval E, Hornby Z, Multani PS, Shaw AT, De Braud FG. Safety and antitumor activity of the multitargeted pan-TRK, ROS1, and ALK inhibitor entrectinib: combined results from two phase I trials (ALKA-372-001 and STARTRK-1). Cancer Discov. 2017 Apr;7(4):400-409. Epub 2017 Feb 9. link to original article link to PMC article contains dosing details in manuscript PubMed NCT02097810
    1. Pooled update: Drilon A, Siena S, Dziadziuszko R, Barlesi F, Krebs MG, Shaw AT, de Braud F, Rolfo C, Ahn MJ, Wolf J, Seto T, Cho BC, Patel MR, Chiu CH, John T, Goto K, Karapetis CS, Arkenau HT, Kim SW, Ohe Y, Li YC, Chae YK, Chung CH, Otterson GA, Murakami H, Lin CC, Tan DSW, Prenen H, Riehl T, Chow-Maneval E, Simmons B, Cui N, Johnson A, Eng S, Wilson TR, Doebele RC; trial investigators. Entrectinib in ROS1 fusion-positive non-small-cell lung cancer: integrated analysis of three phase 1-2 trials. Lancet Oncol. 2020 Feb;21(2):261-270. Epub 2019 Dec 11. Erratum in: Lancet Oncol. 2020 Feb;21(2):e70. Erratum in: Lancet Oncol. 2020 Jul;21(7):e341. link to original article link to PMC article PubMed
    2. Pooled update: Dziadziuszko R, Krebs MG, De Braud F, Siena S, Drilon A, Doebele RC, Patel MR, Cho BC, Liu SV, Ahn MJ, Chiu CH, Farago AF, Lin CC, Karapetis CS, Li YC, Day BM, Chen D, Wilson TR, Barlesi F. Updated Integrated Analysis of the Efficacy and Safety of Entrectinib in Locally Advanced or Metastatic ROS1 Fusion-Positive Non-Small-Cell Lung Cancer. J Clin Oncol. 2021 Apr 10;39(11):1253-1263. Epub 2021 Mar 1. link to original article link to PMC article PubMed

Repotrectinib monotherapy

Regimen

FDA-recommended dose
Study Dates of enrollment Evidence
Drilon et al. 2024 (TRIDENT-1) 2017-02-27 to 2022-12-19 Phase 1/2 (RT)

Targeted therapy

  • Repotrectinib (Augtyro) as follows:
    • Cycle 1: 160 mg PO once per day on days 1 to 14, then 160 mg PO twice per day on days 15 to 28
    • Cycle 2 onwards: 160 mg PO twice per day on days 1 to 28

28-day cycles

References

  1. TRIDENT-1: Drilon A, Camidge DR, Lin JJ, Kim SW, Solomon BJ, Dziadziuszko R, Besse B, Goto K, de Langen AJ, Wolf J, Lee KH, Popat S, Springfeld C, Nagasaka M, Felip E, Yang N, Velcheti V, Lu S, Kao S, Dooms C, Krebs MG, Yao W, Beg MS, Hu X, Moro-Sibilot D, Cheema P, Stopatschinskaja S, Mehta M, Trone D, Graber A, Sims G, Yuan Y, Cho BC; TRIDENT-1 Investigators. Repotrectinib in ROS1 Fusion-Positive Non-Small-Cell Lung Cancer. N Engl J Med. 2024 Jan 11;390(2):118-131. link to original article contains dosing details in abstract PubMed NCT03093116

Advanced or metastatic disease, ROS1 inhibitor-exposed

Lorlatinib monotherapy

Regimen

Study Dates of enrollment Evidence
Shaw et al. 2017 (B7461001) 2014-2016 Phase 1/2

Targeted therapy

28-day cycles

References

  1. B7461001: Shaw AT, Felip E, Bauer TM, Besse B, Navarro A, Postel-Vinay S, Gainor JF, Johnson M, Dietrich J, James LP, Clancy JS, Chen J, Martini JF, Abbattista A, Solomon BJ. Lorlatinib in non-small-cell lung cancer with ALK or ROS1 rearrangement: an international, multicentre, open-label, single-arm first-in-man phase 1 trial. Lancet Oncol. 2017 Dec;18(12):1590-1599. Epub 2017 Oct 23. link to original article contains dosing details in abstract link to PMC article PubMed NCT01970865
    1. Update: Shaw AT, Solomon BJ, Chiari R, Riely GJ, Besse B, Soo RA, Kao S, Lin CC, Bauer TM, Clancy JS, Thurm H, Martini JF, Peltz G, Abbattista A, Li S, Ou SI. Lorlatinib in advanced ROS1-positive non-small-cell lung cancer: a multicentre, open-label, single-arm, phase 1-2 trial. Lancet Oncol. 2019 Dec;20(12):1691-1701. Epub 2019 Oct 25. link to original article PubMed

Repotrectinib monotherapy

Regimen

FDA-recommended dose
Study Dates of enrollment Evidence
Drilon et al. 2024 (TRIDENT-1) 2017-02-27 to 2022-12-19 Phase 1/2 (RT)

Targeted therapy

  • Repotrectinib (Augtyro) as follows:
    • Cycle 1: 160 mg PO once per day on days 1 to 14, then 160 mg PO twice per day on days 15 to 28
    • Cycle 2 onwards: 160 mg PO twice per day on days 1 to 28

28-day cycles

References

  1. TRIDENT-1: Drilon A, Camidge DR, Lin JJ, Kim SW, Solomon BJ, Dziadziuszko R, Besse B, Goto K, de Langen AJ, Wolf J, Lee KH, Popat S, Springfeld C, Nagasaka M, Felip E, Yang N, Velcheti V, Lu S, Kao S, Dooms C, Krebs MG, Yao W, Beg MS, Hu X, Moro-Sibilot D, Cheema P, Stopatschinskaja S, Mehta M, Trone D, Graber A, Sims G, Yuan Y, Cho BC; TRIDENT-1 Investigators. Repotrectinib in ROS1 Fusion-Positive Non-Small-Cell Lung Cancer. N Engl J Med. 2024 Jan 11;390(2):118-131. link to original article contains dosing details in abstract PubMed NCT03093116

Additional resources

Retrieved from "https://hemonc.org/w/index.php?title=Non-small_cell_lung_cancer,_ROS1-positive&oldid=87990"