Difference between revisions of "Gastric cancer, HER2-positive"
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[[#top|Back to Top]] | [[#top|Back to Top]] | ||
</div> | </div> | ||
− | {{#lst: | + | {{#lst:Editorial board transclusions|gi}} |
− | + | '''Note: these are regimens tested in biomarker-specific populations and includes gastric and gastroesophageal cancers. Please see the [[gastric cancer|main gastric cancer page]] or the [[esophageal cancer|main esophageal cancer page]] for other regimens.''' | |
{| class="wikitable" style="float:right; margin-right: 5px;" | {| class="wikitable" style="float:right; margin-right: 5px;" | ||
|- | |- | ||
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{{TOC limit|limit=3}} | {{TOC limit|limit=3}} | ||
=Guidelines= | =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.''' | ||
==CAP/ASCP/ASCO== | ==CAP/ASCP/ASCO== | ||
− | *'''2017:''' Bartley et al. [https://doi.org/10.1200/JCO.2016.69.4836 HER2 testing and clinical decision making in gastroesophageal adenocarcinoma] [https://pubmed.ncbi.nlm.nih.gov/28129524 PubMed] | + | *'''2017:''' Bartley et al. [https://doi.org/10.1200/JCO.2016.69.4836 HER2 testing and clinical decision making in gastroesophageal adenocarcinoma] [https://pubmed.ncbi.nlm.nih.gov/28129524/ PubMed] |
+ | ==NCCN== | ||
+ | *''NCCN does not currently have guidelines at this granular level; please see [https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1433 NCCN Guidelines - Esophageal and Esophagogastric Junction Cancers] and [https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1434 NCCN Guidelines - Gastric Cancer].'' | ||
+ | |||
=Metastatic or locally advanced disease, first-line= | =Metastatic or locally advanced disease, first-line= | ||
==Capecitabine & Cisplatin (CX) {{#subobject:c58325|Regimen=1}}== | ==Capecitabine & Cisplatin (CX) {{#subobject:c58325|Regimen=1}}== | ||
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{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
!style="width: 20%"|Study | !style="width: 20%"|Study | ||
− | !style="width: 20%"| | + | !style="width: 20%"|Dates of enrollment |
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
!style="width: 20%"|Comparator | !style="width: 20%"|Comparator | ||
Line 30: | Line 34: | ||
|2005-2008 | |2005-2008 | ||
| style="background-color:#1a9851" |Phase 3 (C-RT) | | style="background-color:#1a9851" |Phase 3 (C-RT) | ||
− | | | + | |1a. [[#Cisplatin_.26_Fluorouracil_.28CF.29_.26_Trastuzumab|CF & Trastuzumab]]<br>1b. [[#Capecitabine_.26_Cisplatin_.28CX.29_.26_Trastuzumab|CX & Trastuzumab]] |
| style="background-color:#d73027" |Inferior OS | | style="background-color:#d73027" |Inferior OS | ||
|- | |- | ||
Line 46: | Line 50: | ||
</div></div> | </div></div> | ||
===References=== | ===References=== | ||
− | #'''ToGA:''' Bang YJ, Van Cutsem E, Feyereislova A, Chung HC, Shen L, Sawaki A, Lordick F, Ohtsu A, Omuro Y, Satoh T, Aprile G, Kulikov E, Hill J, Lehle M, Rüschoff J, Kang YK; ToGA Trial Investigators. Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer (ToGA): a phase 3, open-label, randomised controlled trial. Lancet. 2010 Aug 28;376(9742):687-97. Epub 2010 Aug 19. [https://doi.org/10.1016/S0140-6736(10)61121-X link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/20728210 PubMed] NCT01041404 | + | #'''ToGA:''' Bang YJ, Van Cutsem E, Feyereislova A, Chung HC, Shen L, Sawaki A, Lordick F, Ohtsu A, Omuro Y, Satoh T, Aprile G, Kulikov E, Hill J, Lehle M, Rüschoff J, Kang YK; ToGA Trial Investigators. Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer (ToGA): a phase 3, open-label, randomised controlled trial. Lancet. 2010 Aug 28;376(9742):687-97. Epub 2010 Aug 19. [https://doi.org/10.1016/S0140-6736(10)61121-X link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/20728210/ PubMed] [https://clinicaltrials.gov/study/NCT01041404 NCT01041404] |
==Capecitabine & Cisplatin (CX) & Trastuzumab {{#subobject:7cbb79|Regimen=1}}== | ==Capecitabine & Cisplatin (CX) & Trastuzumab {{#subobject:7cbb79|Regimen=1}}== | ||
CX & Trastuzumab: '''<u>C</u>'''isplatin, '''<u>X</u>'''eloda (Capecitabine), Trastuzumab | CX & Trastuzumab: '''<u>C</u>'''isplatin, '''<u>X</u>'''eloda (Capecitabine), Trastuzumab | ||
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{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
! style="width: 20%" |Study | ! style="width: 20%" |Study | ||
− | ! style="width: 20%" | | + | ! style="width: 20%" |Dates of enrollment |
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]] | ! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]] | ||
! style="width: 20%" |Comparator | ! style="width: 20%" |Comparator | ||
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<div class="toccolours" style="background-color:#b3e2cd"> | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | *[[Cisplatin (Platinol)]] 80 mg/m<sup>2</sup> IV once on day 1 | + | *[[Cisplatin (Platinol)]] as follows: |
− | *[[Capecitabine (Xeloda)]] 800 mg/m<sup>2</sup> PO twice per day on days 1 to 14 | + | **Cycles 1 to 6: 80 mg/m<sup>2</sup> IV once on day 1 |
+ | *[[Capecitabine (Xeloda)]] as follows: | ||
+ | **Cycles 1 to 6: 800 mg/m<sup>2</sup> PO twice per day on days 1 to 14 | ||
====Targeted therapy==== | ====Targeted therapy==== | ||
*[[Trastuzumab (Herceptin)]] as follows: | *[[Trastuzumab (Herceptin)]] as follows: | ||
**Cycle 1: 8 mg/kg IV once on day 1 | **Cycle 1: 8 mg/kg IV once on day 1 | ||
− | **Cycle | + | **Cycles 2 to 6: 6 mg/kg IV once on day 1 |
− | '''21-day | + | **Cycle 7 onwards: 10 mg/kg IV once on day 1 |
− | + | '''21-day cycles''' | |
− | |||
− | |||
− | |||
</div></div><br> | </div></div><br> | ||
<div class="toccolours" style="background-color:#eeeeee"> | <div class="toccolours" style="background-color:#eeeeee"> | ||
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{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
! style="width: 20%" |Study | ! style="width: 20%" |Study | ||
− | ! style="width: 20%" | | + | ! style="width: 20%" |Dates of enrollment |
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]] | ! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]] | ||
! style="width: 20%" |Comparator | ! style="width: 20%" |Comparator | ||
Line 94: | Line 97: | ||
|- | |- | ||
|[https://doi.org/10.1016/S0140-6736(10)61121-X Bang et al. 2010 (ToGA)] | |[https://doi.org/10.1016/S0140-6736(10)61121-X Bang et al. 2010 (ToGA)] | ||
+ | <!-- {| class="wikitable" style="margin:auto; color:white; background-color:#1B4F26" | ||
+ | |'''[https://www.esmo.org/guidelines/esmo-mcbs/esmo-mcbs-scorecards/scorecard-295-1 <span style="color:white;">ESMO-MCBS (3)</span>]''' | ||
+ | |- | ||
+ | |} --> | ||
|2005-2008 | |2005-2008 | ||
| style="background-color:#1a9851" |Phase 3 (E-RT-esc) | | style="background-color:#1a9851" |Phase 3 (E-RT-esc) | ||
− | | | + | |1a. [[#Cisplatin_.26_Fluorouracil_.28CF.29_4|CF]]<br>1b. [[#Capecitabine_.26_Cisplatin_.28CX.29|CX]] |
− | | style="background-color:#1a9850" |Superior OS<br>Median OS: 13.8 vs 11.1 mo<br>(HR 0.74, 95% CI 0.60-0.91) | + | | style="background-color:#1a9850" |Superior OS (primary endpoint)<br>Median OS: 13.8 vs 11.1 mo<br>(HR 0.74, 95% CI 0.60-0.91) |
|- | |- | ||
|[https://doi.org/10.1016/S1470-2045(18)30481-9 Tabernero et al. 2018 (JACOB)] | |[https://doi.org/10.1016/S1470-2045(18)30481-9 Tabernero et al. 2018 (JACOB)] | ||
|2013-2016 | |2013-2016 | ||
| style="background-color:#1a9851" |Phase 3 (C) | | style="background-color:#1a9851" |Phase 3 (C) | ||
− | |[[#Capecitabine_.26_Cisplatin_.28CX.29.2C_Pertuzumab. | + | |[[#Capecitabine_.26_Cisplatin_.28CX.29.2C_Pertuzumab.2C_Trastuzumab|CX, Pertuzumab, Trastuzumab]] |
| style="background-color:#fc8d59" |Seems to have inferior OS<sup>1</sup><br>Median OS: 14.2 vs 18.1 mo<br>(HR 1.18, 95% CI 1.01-1.39) | | style="background-color:#fc8d59" |Seems to have inferior OS<sup>1</sup><br>Median OS: 14.2 vs 18.1 mo<br>(HR 1.18, 95% CI 1.01-1.39) | ||
|- | |- | ||
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</div></div> | </div></div> | ||
===References=== | ===References=== | ||
− | #'''ToGA:''' Bang YJ, Van Cutsem E, Feyereislova A, Chung HC, Shen L, Sawaki A, Lordick F, Ohtsu A, Omuro Y, Satoh T, Aprile G, Kulikov E, Hill J, Lehle M, Rüschoff J, Kang YK; ToGA Trial Investigators. Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer (ToGA): a phase 3, open-label, randomised controlled trial. Lancet. 2010 Aug 28;376(9742):687-97. Epub 2010 Aug 19. [https://doi.org/10.1016/S0140-6736(10)61121-X link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/20728210 PubMed] NCT01041404 | + | #'''ToGA:''' Bang YJ, Van Cutsem E, Feyereislova A, Chung HC, Shen L, Sawaki A, Lordick F, Ohtsu A, Omuro Y, Satoh T, Aprile G, Kulikov E, Hill J, Lehle M, Rüschoff J, Kang YK; ToGA Trial Investigators. Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer (ToGA): a phase 3, open-label, randomised controlled trial. Lancet. 2010 Aug 28;376(9742):687-97. Epub 2010 Aug 19. [https://doi.org/10.1016/S0140-6736(10)61121-X link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/20728210/ PubMed] [https://clinicaltrials.gov/study/NCT01041404 NCT01041404] |
− | #'''HELOISE:''' Shah MA, Xu RH, Bang YJ, Hoff PM, Liu T, Herráez-Baranda LA, Xia F, Garg A, Shing M, Tabernero J. HELOISE: Phase IIIb randomized multicenter study comparing standard-of-care and higher-dose trastuzumab regimens combined with chemotherapy as first-line therapy in patients with human epidermal growth factor receptor 2-positive metastatic gastric or gastroesophageal junction adenocarcinoma. J Clin Oncol. 2017 Aug 1;35(22):2558-2567. Epub 2017 Jun 2.[https://doi.org/10.1200/JCO.2016.71.6852 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/28574779 PubMed] NCT01450696 | + | #'''HELOISE:''' Shah MA, Xu RH, Bang YJ, Hoff PM, Liu T, Herráez-Baranda LA, Xia F, Garg A, Shing M, Tabernero J. HELOISE: Phase IIIb randomized multicenter study comparing standard-of-care and higher-dose trastuzumab regimens combined with chemotherapy as first-line therapy in patients with human epidermal growth factor receptor 2-positive metastatic gastric or gastroesophageal junction adenocarcinoma. J Clin Oncol. 2017 Aug 1;35(22):2558-2567. Epub 2017 Jun 2. [https://doi.org/10.1200/JCO.2016.71.6852 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/28574779/ PubMed] [https://clinicaltrials.gov/study/NCT01450696 NCT01450696] |
− | #'''JACOB:''' Tabernero J, Hoff PM, Shen L, Ohtsu A, Shah MA, Cheng K, Song C, Wu H, Eng-Wong J, Kim K, Kang YK. Pertuzumab plus trastuzumab and chemotherapy for HER2-positive metastatic gastric or gastro-oesophageal junction cancer (JACOB): final analysis of a double-blind, randomised, placebo-controlled phase 3 study. Lancet Oncol. 2018 Oct;19(10):1372-1384. Epub 2018 Sep 11. [https://doi.org/10.1016/S1470-2045(18)30481-9 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/30217672 PubMed] NCT01774786 | + | #'''JACOB:''' Tabernero J, Hoff PM, Shen L, Ohtsu A, Shah MA, Cheng K, Song C, Wu H, Eng-Wong J, Kim K, Kang YK. Pertuzumab plus trastuzumab and chemotherapy for HER2-positive metastatic gastric or gastro-oesophageal junction cancer (JACOB): final analysis of a double-blind, randomised, placebo-controlled phase 3 study. Lancet Oncol. 2018 Oct;19(10):1372-1384. Epub 2018 Sep 11. [https://doi.org/10.1016/S1470-2045(18)30481-9 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/30217672/ PubMed] [https://clinicaltrials.gov/study/NCT01774786 NCT01774786] |
− | ##'''Update:''' Tabernero J, Hoff PM, Shen L, Ohtsu A, Shah MA, Siddiqui A, Heeson S, Kiermaier A, Macharia H, Restuccia E, Kang YK. Pertuzumab, trastuzumab, and chemotherapy in HER2-positive gastric/gastroesophageal junction cancer: end-of-study analysis of the JACOB phase III randomized clinical trial. Gastric Cancer. 2023 Jan;26(1):123-131. Epub 2022 Sep 6. [https://doi.org/10.1007/s10120-022-01335-4 link to original article] [ | + | ##'''Update:''' Tabernero J, Hoff PM, Shen L, Ohtsu A, Shah MA, Siddiqui A, Heeson S, Kiermaier A, Macharia H, Restuccia E, Kang YK. Pertuzumab, trastuzumab, and chemotherapy in HER2-positive gastric/gastroesophageal junction cancer: end-of-study analysis of the JACOB phase III randomized clinical trial. Gastric Cancer. 2023 Jan;26(1):123-131. Epub 2022 Sep 6. [https://doi.org/10.1007/s10120-022-01335-4 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc9813086/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/36066725/ PubMed] |
− | + | ==Capecitabine & Cisplatin (CX), Pertuzumab, Trastuzumab {{#subobject:7chb3c|Regimen=1}}== | |
+ | CX, Pertuzumab, Trastuzumab: '''<u>C</u>'''isplatin, '''<u>X</u>'''eloda (Capecitabine), Pertuzumab, Trastuzumab | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
+ | ===Regimen {{#subobject:pjvvg3|Variant=1}}=== | ||
+ | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
+ | !style="width: 20%"|Study | ||
+ | !style="width: 20%"|Dates of enrollment | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | !style="width: 20%"|Comparator | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
+ | |- | ||
+ | |[https://doi.org/10.1016/S1470-2045(18)30481-9 Tabernero et al. 2018 (JACOB)] | ||
+ | |2013-2016 | ||
+ | | style="background-color:#1a9851" |Phase 3 (E-esc) | ||
+ | |[[#Capecitabine_.26_Cisplatin_.28CX.29_.26_Trastuzumab|CX & Trastuzumab]] | ||
+ | | style="background-color:#91cf60" |Seems to have superior OS<sup>1</sup> (primary endpoint)<br>Median OS: 18.1 vs 14.2 mo<br>(HR 0.85, 95% CI 0.72-0.99) | ||
+ | |- | ||
+ | |} | ||
+ | ''<sup>1</sup>Reported efficacy is based on the 2022 update.'' | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Chemotherapy==== | ||
+ | *[[Cisplatin (Platinol)]] 80 mg/m<sup>2</sup> IV once on day 1 | ||
+ | *[[Capecitabine (Xeloda)]] 1000 mg/m<sup>2</sup> PO twice per day on days 1 to 14 | ||
+ | ====Targeted therapy==== | ||
+ | *[[Pertuzumab (Perjeta)]] 840 mg IV once on day 1 | ||
+ | *[[Trastuzumab (Herceptin)]] as follows: | ||
+ | **Cycle 1: 8 mg/kg IV once on day 1 | ||
+ | **Cycle 2 onwards: 6 mg/kg IV once on day 1 | ||
+ | '''21-day cycles''' | ||
+ | </div></div> | ||
+ | ===References=== | ||
+ | #'''JACOB:''' Tabernero J, Hoff PM, Shen L, Ohtsu A, Shah MA, Cheng K, Song C, Wu H, Eng-Wong J, Kim K, Kang YK. Pertuzumab plus trastuzumab and chemotherapy for HER2-positive metastatic gastric or gastro-oesophageal junction cancer (JACOB): final analysis of a double-blind, randomised, placebo-controlled phase 3 study. Lancet Oncol. 2018 Oct;19(10):1372-1384. Epub 2018 Sep 11. [https://doi.org/10.1016/S1470-2045(18)30481-9 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/30217672/ PubMed] [https://clinicaltrials.gov/study/NCT01774786 NCT01774786] | ||
+ | ##'''Update:''' Tabernero J, Hoff PM, Shen L, Ohtsu A, Shah MA, Siddiqui A, Heeson S, Kiermaier A, Macharia H, Restuccia E, Kang YK. Pertuzumab, trastuzumab, and chemotherapy in HER2-positive gastric/gastroesophageal junction cancer: end-of-study analysis of the JACOB phase III randomized clinical trial. Gastric Cancer. 2023 Jan;26(1):123-131. Epub 2022 Sep 6. [https://doi.org/10.1007/s10120-022-01335-4 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc9813086/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/36066725/ PubMed] | ||
==CapeOx {{#subobject:c699c3|Regimen=1}}== | ==CapeOx {{#subobject:c699c3|Regimen=1}}== | ||
CapeOx: '''<u>Cape</u>'''citabine and '''<u>Ox</u>'''aliplatin | CapeOx: '''<u>Cape</u>'''citabine and '''<u>Ox</u>'''aliplatin | ||
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{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
!style="width: 20%"|Study | !style="width: 20%"|Study | ||
− | !style="width: 20%"| | + | !style="width: 20%"|Dates of enrollment |
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
!style="width: 20%"|Comparator | !style="width: 20%"|Comparator | ||
Line 142: | Line 181: | ||
|2008-2012 | |2008-2012 | ||
| style="background-color:#1a9851" |Phase 3 (C) | | style="background-color:#1a9851" |Phase 3 (C) | ||
− | |[[#CapeOx_. | + | |[[#CapeOx_.26_Lapatinib_999|CapeOx & Lapatinib]] |
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS<br>Median OS: 10.5 vs 12.2 mo<br>(HR 1.10, 95% CI 0.89-1.37) | | style="background-color:#ffffbf" |Did not meet primary endpoint of OS<br>Median OS: 10.5 vs 12.2 mo<br>(HR 1.10, 95% CI 0.89-1.37) | ||
|- | |- | ||
Line 158: | Line 197: | ||
</div></div> | </div></div> | ||
===References=== | ===References=== | ||
− | #'''LOGiC:''' Hecht JR, Bang YJ, Qin SK, Chung HC, Xu JM, Park JO, Jeziorski K, Shparyk Y, Hoff PM, Sobrero A, Salman P, Li J, Protsenko SA, Wainberg ZA, Buyse M, Afenjar K, Houé V, Garcia A, Kaneko T, Huang Y, Khan-Wasti S, Santillana S, Press MF, Slamon D. Lapatinib in combination with capecitabine plus oxaliplatin in human epidermal growth factor receptor 2-positive advanced or metastatic gastric, esophageal, or gastroesophageal adenocarcinoma: TRIO-013/LOGiC--a randomized phase III trial. J Clin Oncol. 2016 Feb 10;34(5):443-51. Epub 2015 Nov 30. [https://doi.org/10.1200/JCO.2015.62.6598 link to original article] [https://pubmed.ncbi.nlm.nih.gov/26628478 PubMed] NCT00680901 | + | #'''LOGiC:''' Hecht JR, Bang YJ, Qin SK, Chung HC, Xu JM, Park JO, Jeziorski K, Shparyk Y, Hoff PM, Sobrero A, Salman P, Li J, Protsenko SA, Wainberg ZA, Buyse M, Afenjar K, Houé V, Garcia A, Kaneko T, Huang Y, Khan-Wasti S, Santillana S, Press MF, Slamon D. Lapatinib in combination with capecitabine plus oxaliplatin in human epidermal growth factor receptor 2-positive advanced or metastatic gastric, esophageal, or gastroesophageal adenocarcinoma: TRIO-013/LOGiC--a randomized phase III trial. J Clin Oncol. 2016 Feb 10;34(5):443-51. Epub 2015 Nov 30. [https://doi.org/10.1200/JCO.2015.62.6598 link to original article] [https://pubmed.ncbi.nlm.nih.gov/26628478/ PubMed] [https://clinicaltrials.gov/study/NCT00680901 NCT00680901] |
− | #'''HERIZON-GEA-01:''' NCT05152147 | + | #'''HERIZON-GEA-01:''' [https://clinicaltrials.gov/study/NCT05152147 NCT05152147] |
==CapeOx, Pembrolizumab, Trastuzumab {{#subobject:gjg8c3|Regimen=1}}== | ==CapeOx, Pembrolizumab, Trastuzumab {{#subobject:gjg8c3|Regimen=1}}== | ||
CapeOx, Pembrolizumab, Trastuzumab: '''<u>Cape</u>'''citabine, '''<u>Ox</u>'''aliplatin, Pembrolizumab, Trastuzumab | CapeOx, Pembrolizumab, Trastuzumab: '''<u>Cape</u>'''citabine, '''<u>Ox</u>'''aliplatin, Pembrolizumab, Trastuzumab | ||
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{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
!style="width: 20%"|Study | !style="width: 20%"|Study | ||
− | !style="width: 20%"| | + | !style="width: 20%"|Dates of enrollment |
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
!style="width: 20%"|Comparator | !style="width: 20%"|Comparator | ||
Line 172: | Line 211: | ||
|- | |- | ||
|[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc8959470/ Janjigian et al. 2021 (KEYNOTE-811)] | |[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc8959470/ Janjigian et al. 2021 (KEYNOTE-811)] | ||
+ | <!-- {| class="wikitable" style="margin:auto; color:white; background-color:#1B4F26" | ||
+ | |'''[https://www.esmo.org/guidelines/esmo-mcbs/esmo-mcbs-scorecards/scorecard-318-1 <span style="color:white;">ESMO-MCBS (2)</span>]''' | ||
+ | |- | ||
+ | |} --> | ||
|2018-2020 | |2018-2020 | ||
| style="background-color:#1a9851" |Phase 3 (E-RT-esc) | | style="background-color:#1a9851" |Phase 3 (E-RT-esc) | ||
− | | | + | |1a. [[#CapeOx_.26_Trastuzumab|CapeOx & Trastuzumab]]<br>1b. [[#Cisplatin_.26_Fluorouracil_.28CF.29_.26_Trastuzumab|CF & Trastuzumab]] |
− | | style="background-color:#1a9850" |Superior | + | | style="background-color:#1a9850" |Superior PFS<sup>1</sup> (co-primary endpoint)<br>Median PFS: 10 vs 8.1 mo<br>(HR 0.73, 95% CI 0.61-0.87)<br><br>Might have superior OS<sup>1</sup> (co-primary endpoint)<br>Median OS: 20 vs 16.8 mo<br>(HR 0.84, 95% CI 0.70-1.01) |
|- | |- | ||
|} | |} | ||
− | ''<sup>1</sup> | + | ''<sup>1</sup>Reported efficacy is based on the 2023 update.'' |
<div class="toccolours" style="background-color:#fdcdac"> | <div class="toccolours" style="background-color:#fdcdac"> | ||
====Biomarker eligibility criteria==== | ====Biomarker eligibility criteria==== | ||
Line 193: | Line 236: | ||
**Cycle 1: 8 mg/kg IV once on day 1 | **Cycle 1: 8 mg/kg IV once on day 1 | ||
**Cycle 2 onwards: 6 mg/kg IV once on day 1 | **Cycle 2 onwards: 6 mg/kg IV once on day 1 | ||
− | '''21-day cycles''' | + | '''21-day cycle for up to 35 cycles (2 years)''' |
</div></div> | </div></div> | ||
===References=== | ===References=== | ||
− | #'''KEYNOTE-811:''' Janjigian YY, Kawazoe A, Yañez P, Li N, Lonardi S, Kolesnik O, Barajas O, Bai Y, Shen L, Tang Y, Wyrwicz LS, Xu J, Shitara K, Qin S, Van Cutsem E, Tabernero J, Li L, Shah S, Bhagia P, Chung HC. The KEYNOTE-811 trial of dual PD-1 and HER2 blockade in HER2-positive gastric cancer. Nature. 2021 Dec;600(7890):727-730. Epub 2021 Dec 15. [https://doi.org/10.1038/s41586-021-04161-3 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc8959470/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/34912120/ PubMed] NCT03615326 | + | #'''KEYNOTE-811:''' Janjigian YY, Kawazoe A, Yañez P, Li N, Lonardi S, Kolesnik O, Barajas O, Bai Y, Shen L, Tang Y, Wyrwicz LS, Xu J, Shitara K, Qin S, Van Cutsem E, Tabernero J, Li L, Shah S, Bhagia P, Chung HC. The KEYNOTE-811 trial of dual PD-1 and HER2 blockade in HER2-positive gastric cancer. Nature. 2021 Dec;600(7890):727-730. Epub 2021 Dec 15. [https://doi.org/10.1038/s41586-021-04161-3 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc8959470/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/34912120/ PubMed] [https://clinicaltrials.gov/study/NCT03615326 NCT03615326] |
+ | ##'''Update:''' Janjigian YY, Kawazoe A, Bai Y, Xu J, Lonardi S, Metges JP, Yanez P, Wyrwicz LS, Shen L, Ostapenko Y, Bilici M, Chung HC, Shitara K, Qin SK, Van Cutsem E, Tabernero J, Li K, Shih CS, Bhagia P, Rha SY; KEYNOTE-811 Investigators. Pembrolizumab plus trastuzumab and chemotherapy for HER2-positive gastric or gastro-oesophageal junction adenocarcinoma: interim analyses from the phase 3 KEYNOTE-811 randomised placebo-controlled trial. Lancet. 2023 Dec 9;402(10418):2197-2208. Epub 2023 Oct 20. [https://doi.org/10.1016/s0140-6736(23)02033-0 link to original article] [https://pubmed.ncbi.nlm.nih.gov/37871604/ PubMed] | ||
==CapeOx & Trastuzumab {{#subobject:gh6cc3|Regimen=1}}== | ==CapeOx & Trastuzumab {{#subobject:gh6cc3|Regimen=1}}== | ||
CapeOx & Trastuzumab: '''<u>Cape</u>'''citabine, '''<u>Ox</u>'''aliplatin, Trastuzumab | CapeOx & Trastuzumab: '''<u>Cape</u>'''citabine, '''<u>Ox</u>'''aliplatin, Trastuzumab | ||
Line 203: | Line 247: | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
!style="width: 20%"|Study | !style="width: 20%"|Study | ||
− | !style="width: 20%"| | + | !style="width: 20%"|Dates of enrollment |
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
!style="width: 20%"|Comparator | !style="width: 20%"|Comparator | ||
Line 211: | Line 255: | ||
|2018-2020 | |2018-2020 | ||
| style="background-color:#1a9851" |Phase 3 (C) | | style="background-color:#1a9851" |Phase 3 (C) | ||
− | | | + | |1a. [[#CapeOx.2C_Pembrolizumab.2C_Trastuzumab|CapeOx, Pembrolizumab, Trastuzumab]]<br>1b. [[#Cisplatin_.26_Fluorouracil_.28CF.29.2C_Pembrolizumab.2C_Trastuzumab|CF, Pembrolizumab, Trastuzumab]] |
− | | style="background-color:#d73027" |Inferior | + | | style="background-color:#d73027" |Inferior PFS<sup>1</sup><br><br>Might have inferior OS<sup>1</sup> |
|- | |- | ||
|} | |} | ||
− | ''<sup>1</sup> | + | ''<sup>1</sup>Reported efficacy is based on the 2023 update.''<br> |
''Note: to our knowledge, this regimen was not tested as an experimental arm in an RCT in this context, prior to becoming a standard comparator arm.'' | ''Note: to our knowledge, this regimen was not tested as an experimental arm in an RCT in this context, prior to becoming a standard comparator arm.'' | ||
<div class="toccolours" style="background-color:#fdcdac"> | <div class="toccolours" style="background-color:#fdcdac"> | ||
Line 232: | Line 276: | ||
</div></div> | </div></div> | ||
===References=== | ===References=== | ||
− | #'''KEYNOTE-811:''' Janjigian YY, Kawazoe A, Yañez P, Li N, Lonardi S, Kolesnik O, Barajas O, Bai Y, Shen L, Tang Y, Wyrwicz LS, Xu J, Shitara K, Qin S, Van Cutsem E, Tabernero J, Li L, Shah S, Bhagia P, Chung HC. The KEYNOTE-811 trial of dual PD-1 and HER2 blockade in HER2-positive gastric cancer. Nature. 2021 Dec;600(7890):727-730. Epub 2021 Dec 15. [https://doi.org/10.1038/s41586-021-04161-3 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc8959470/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/34912120/ PubMed] NCT03615326 | + | #'''KEYNOTE-811:''' Janjigian YY, Kawazoe A, Yañez P, Li N, Lonardi S, Kolesnik O, Barajas O, Bai Y, Shen L, Tang Y, Wyrwicz LS, Xu J, Shitara K, Qin S, Van Cutsem E, Tabernero J, Li L, Shah S, Bhagia P, Chung HC. The KEYNOTE-811 trial of dual PD-1 and HER2 blockade in HER2-positive gastric cancer. Nature. 2021 Dec;600(7890):727-730. Epub 2021 Dec 15. [https://doi.org/10.1038/s41586-021-04161-3 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc8959470/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/34912120/ PubMed] [https://clinicaltrials.gov/study/NCT03615326 NCT03615326] |
+ | ##'''Update:''' Janjigian YY, Kawazoe A, Bai Y, Xu J, Lonardi S, Metges JP, Yanez P, Wyrwicz LS, Shen L, Ostapenko Y, Bilici M, Chung HC, Shitara K, Qin SK, Van Cutsem E, Tabernero J, Li K, Shih CS, Bhagia P, Rha SY; KEYNOTE-811 Investigators. Pembrolizumab plus trastuzumab and chemotherapy for HER2-positive gastric or gastro-oesophageal junction adenocarcinoma: interim analyses from the phase 3 KEYNOTE-811 randomised placebo-controlled trial. Lancet. 2023 Dec 9;402(10418):2197-2208. Epub 2023 Oct 20. [https://doi.org/10.1016/s0140-6736(23)02033-0 link to original article] [https://pubmed.ncbi.nlm.nih.gov/37871604/ PubMed] | ||
==Cisplatin & Fluorouracil (CF) {{#subobject:4d9936|Regimen=1}}== | ==Cisplatin & Fluorouracil (CF) {{#subobject:4d9936|Regimen=1}}== | ||
CF: '''<u>C</u>'''isplatin & '''<u>F</u>'''luorouracil | CF: '''<u>C</u>'''isplatin & '''<u>F</u>'''luorouracil | ||
Line 240: | Line 285: | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
! style="width: 20%" |Study | ! style="width: 20%" |Study | ||
− | ! style="width: 20%" | | + | ! style="width: 20%" |Dates of enrollment |
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]] | ! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]] | ||
! style="width: 20%" |Comparator | ! style="width: 20%" |Comparator | ||
Line 248: | Line 293: | ||
|2005-2008 | |2005-2008 | ||
| style="background-color:#1a9851" |Phase 3 (C) | | style="background-color:#1a9851" |Phase 3 (C) | ||
− | | | + | |1a. [[#Cisplatin_.26_Fluorouracil_.28CF.29_.26_Trastuzumab|CF & Trastuzumab]]<br>1b. [[#Capecitabine_.26_Cisplatin_.28CX.29_.26_Trastuzumab|CX & Trastuzumab]] |
| style="background-color:#d73027" |Inferior OS | | style="background-color:#d73027" |Inferior OS | ||
|- | |- | ||
Line 264: | Line 309: | ||
</div></div> | </div></div> | ||
===References=== | ===References=== | ||
− | #'''ToGA:''' Bang YJ, Van Cutsem E, Feyereislova A, Chung HC, Shen L, Sawaki A, Lordick F, Ohtsu A, Omuro Y, Satoh T, Aprile G, Kulikov E, Hill J, Lehle M, Rüschoff J, Kang YK; ToGA Trial Investigators. Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer (ToGA): a phase 3, open-label, randomised controlled trial. Lancet. 2010 Aug 28;376(9742):687-97. Epub 2010 Aug 19. [https://doi.org/10.1016/S0140-6736(10)61121-X link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/20728210 PubMed] NCT01041404 | + | #'''ToGA:''' Bang YJ, Van Cutsem E, Feyereislova A, Chung HC, Shen L, Sawaki A, Lordick F, Ohtsu A, Omuro Y, Satoh T, Aprile G, Kulikov E, Hill J, Lehle M, Rüschoff J, Kang YK; ToGA Trial Investigators. Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer (ToGA): a phase 3, open-label, randomised controlled trial. Lancet. 2010 Aug 28;376(9742):687-97. Epub 2010 Aug 19. [https://doi.org/10.1016/S0140-6736(10)61121-X link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/20728210/ PubMed] [https://clinicaltrials.gov/study/NCT01041404 NCT01041404] |
==Cisplatin & Fluorouracil (CF) & Trastuzumab {{#subobject:ca9cd1|Regimen=1}}== | ==Cisplatin & Fluorouracil (CF) & Trastuzumab {{#subobject:ca9cd1|Regimen=1}}== | ||
CF & Trastuzumab: '''<u>C</u>'''isplatin, '''<u>F</u>'''luorouracil, Trastuzumab | CF & Trastuzumab: '''<u>C</u>'''isplatin, '''<u>F</u>'''luorouracil, Trastuzumab | ||
Line 271: | Line 316: | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
!style="width: 20%"|Study | !style="width: 20%"|Study | ||
− | !style="width: 20%"| | + | !style="width: 20%"|Dates of enrollment |
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
!style="width: 20%"|Comparator | !style="width: 20%"|Comparator | ||
Line 277: | Line 322: | ||
|- | |- | ||
|[https://doi.org/10.1016/S0140-6736(10)61121-X Bang et al. 2010 (ToGA)] | |[https://doi.org/10.1016/S0140-6736(10)61121-X Bang et al. 2010 (ToGA)] | ||
+ | <!-- {| class="wikitable" style="margin:auto; color:white; background-color:#1B4F26" | ||
+ | |'''[https://www.esmo.org/guidelines/esmo-mcbs/esmo-mcbs-scorecards/scorecard-295-1 <span style="color:white;">ESMO-MCBS (3)</span>]''' | ||
+ | |- | ||
+ | |} --> | ||
|2005-2008 | |2005-2008 | ||
− | | style="background-color:#1a9851" |Phase 3 (E-esc) | + | | style="background-color:#1a9851" |Phase 3 (E-RT-esc) |
− | | | + | |1a. [[#Cisplatin_.26_Fluorouracil_.28CF.29_4|CF]]<br>1b. [[#Capecitabine_.26_Cisplatin_.28CX.29|CX]] |
− | | style="background-color:#1a9850" |Superior OS<br>Median OS: 13.8 vs 11.1 mo<br>(HR 0.74, 95% CI 0.60-0.91) | + | | style="background-color:#1a9850" |Superior OS (primary endpoint)<br>Median OS: 13.8 vs 11.1 mo<br>(HR 0.74, 95% CI 0.60-0.91) |
+ | |- | ||
+ | |[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc8959470/ Janjigian et al. 2021 (KEYNOTE-811)] | ||
+ | |2018-2020 | ||
+ | | style="background-color:#1a9851" |Phase 3 (C) | ||
+ | |1a. [[#CapeOx.2C_Pembrolizumab.2C_Trastuzumab|CapeOx, Pembrolizumab, Trastuzumab]]<br>1b. [[#Cisplatin_.26_Fluorouracil_.28CF.29.2C_Pembrolizumab.2C_Trastuzumab|CF, Pembrolizumab, Trastuzumab]] | ||
+ | | style="background-color:#d73027" |Inferior PFS<sup>1</sup><br><br>Might have inferior OS<sup>1</sup> | ||
|- | |- | ||
|} | |} | ||
+ | ''<sup>1</sup>Reported efficacy is based on the 2023 update.''<br> | ||
''Patients: 100% adenocarcinoma (19% gastroesophageal junction, 81% gastric). 10% with ECOG of 2.'' | ''Patients: 100% adenocarcinoma (19% gastroesophageal junction, 81% gastric). 10% with ECOG of 2.'' | ||
<div class="toccolours" style="background-color:#fdcdac"> | <div class="toccolours" style="background-color:#fdcdac"> | ||
Line 299: | Line 355: | ||
</div></div> | </div></div> | ||
===References=== | ===References=== | ||
− | #'''ToGA:''' Bang YJ, Van Cutsem E, Feyereislova A, Chung HC, Shen L, Sawaki A, Lordick F, Ohtsu A, Omuro Y, Satoh T, Aprile G, Kulikov E, Hill J, Lehle M, Rüschoff J, Kang YK; ToGA Trial Investigators. Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer (ToGA): a phase 3, open-label, randomised controlled trial. Lancet. 2010 Aug 28;376(9742):687-97. Epub 2010 Aug 19. [https://doi.org/10.1016/S0140-6736(10)61121-X link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/20728210 PubMed] NCT01041404 | + | #'''ToGA:''' Bang YJ, Van Cutsem E, Feyereislova A, Chung HC, Shen L, Sawaki A, Lordick F, Ohtsu A, Omuro Y, Satoh T, Aprile G, Kulikov E, Hill J, Lehle M, Rüschoff J, Kang YK; ToGA Trial Investigators. Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer (ToGA): a phase 3, open-label, randomised controlled trial. Lancet. 2010 Aug 28;376(9742):687-97. Epub 2010 Aug 19. [https://doi.org/10.1016/S0140-6736(10)61121-X link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/20728210/ PubMed] [https://clinicaltrials.gov/study/NCT01041404 NCT01041404] |
− | #'''HERIZON-GEA-01:''' NCT05152147 | + | #'''KEYNOTE-811:''' Janjigian YY, Kawazoe A, Yañez P, Li N, Lonardi S, Kolesnik O, Barajas O, Bai Y, Shen L, Tang Y, Wyrwicz LS, Xu J, Shitara K, Qin S, Van Cutsem E, Tabernero J, Li L, Shah S, Bhagia P, Chung HC. The KEYNOTE-811 trial of dual PD-1 and HER2 blockade in HER2-positive gastric cancer. Nature. 2021 Dec;600(7890):727-730. Epub 2021 Dec 15. [https://doi.org/10.1038/s41586-021-04161-3 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc8959470/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/34912120/ PubMed] [https://clinicaltrials.gov/study/NCT03615326 NCT03615326] |
− | #'''KEYNOTE-811:''' NCT03615326 | + | ##'''Update:''' Janjigian YY, Kawazoe A, Bai Y, Xu J, Lonardi S, Metges JP, Yanez P, Wyrwicz LS, Shen L, Ostapenko Y, Bilici M, Chung HC, Shitara K, Qin SK, Van Cutsem E, Tabernero J, Li K, Shih CS, Bhagia P, Rha SY; KEYNOTE-811 Investigators. Pembrolizumab plus trastuzumab and chemotherapy for HER2-positive gastric or gastro-oesophageal junction adenocarcinoma: interim analyses from the phase 3 KEYNOTE-811 randomised placebo-controlled trial. Lancet. 2023 Dec 9;402(10418):2197-2208. Epub 2023 Oct 20. [https://doi.org/10.1016/s0140-6736(23)02033-0 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/37871604/ PubMed] |
+ | #'''HERIZON-GEA-01:''' [https://clinicaltrials.gov/study/NCT05152147 NCT05152147] | ||
+ | ==Cisplatin & Fluorouracil (CF), Pembrolizumab, Trastuzumab {{#subobject:cfg8c3|Regimen=1}}== | ||
+ | CF, Pembrolizumab, Trastuzumab: '''<u>C</u>'''isplatin, '''<u>F</u>'''luorouracil, Pembrolizumab, Trastuzumab | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
+ | ===Regimen {{#subobject:y15bc0|Variant=1}}=== | ||
+ | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
+ | !style="width: 20%"|Study | ||
+ | !style="width: 20%"|Dates of enrollment | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | !style="width: 20%"|Comparator | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
+ | |- | ||
+ | |[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc8959470/ Janjigian et al. 2021 (KEYNOTE-811)] | ||
+ | <!-- {| class="wikitable" style="margin:auto; color:white; background-color:#1B4F26" | ||
+ | |'''[https://www.esmo.org/guidelines/esmo-mcbs/esmo-mcbs-scorecards/scorecard-318-1 <span style="color:white;">ESMO-MCBS (2)</span>]''' | ||
+ | |- | ||
+ | |} --> | ||
+ | |2018-2020 | ||
+ | | style="background-color:#1a9851" |Phase 3 (E-RT-esc) | ||
+ | |1a. [[#CapeOx_.26_Trastuzumab|CapeOx & Trastuzumab]]<br>1b. [[#Cisplatin_.26_Fluorouracil_.28CF.29_.26_Trastuzumab|CF & Trastuzumab]] | ||
+ | | style="background-color:#1a9850" |Superior PFS<sup>1</sup> (co-primary endpoint)<br>Median PFS: 10 vs 8.1 mo<br>(HR 0.73, 95% CI 0.61-0.87)<br><br>Might have superior OS<sup>1</sup> (co-primary endpoint)<br>Median OS: 20 vs 16.8 mo<br>(HR 0.84, 95% CI 0.70-1.01) | ||
+ | |- | ||
+ | |} | ||
+ | ''<sup>1</sup>Reported efficacy is based on the 2023 update.'' | ||
+ | <div class="toccolours" style="background-color:#fdcdac"> | ||
+ | ====Biomarker eligibility criteria==== | ||
+ | *HER2 positive | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Chemotherapy==== | ||
+ | *[[Cisplatin (Platinol)]] 80 mg/m<sup>2</sup> IV once on day 1 | ||
+ | *[[Fluorouracil (5-FU)]] 800 mg/m<sup>2</sup>/day IV continuous infusion over 120 hours, started on day 1 (total dose per cycle: 4000 mg/m<sup>2</sup>) | ||
+ | ====Immunotherapy==== | ||
+ | *[[Pembrolizumab (Keytruda)]] 200 mg IV once on day 1 | ||
+ | ====Targeted therapy==== | ||
+ | *[[Trastuzumab (Herceptin)]] as follows: | ||
+ | **Cycle 1: 8 mg/kg IV once on day 1 | ||
+ | **Cycle 2 onwards: 6 mg/kg IV once on day 1 | ||
+ | '''21-day cycles''' | ||
+ | </div></div> | ||
+ | ===References=== | ||
+ | #'''KEYNOTE-811:''' Janjigian YY, Kawazoe A, Yañez P, Li N, Lonardi S, Kolesnik O, Barajas O, Bai Y, Shen L, Tang Y, Wyrwicz LS, Xu J, Shitara K, Qin S, Van Cutsem E, Tabernero J, Li L, Shah S, Bhagia P, Chung HC. The KEYNOTE-811 trial of dual PD-1 and HER2 blockade in HER2-positive gastric cancer. Nature. 2021 Dec;600(7890):727-730. Epub 2021 Dec 15. [https://doi.org/10.1038/s41586-021-04161-3 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc8959470/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/34912120/ PubMed] [https://clinicaltrials.gov/study/NCT03615326 NCT03615326] | ||
+ | ##'''Update:''' Janjigian YY, Kawazoe A, Bai Y, Xu J, Lonardi S, Metges JP, Yanez P, Wyrwicz LS, Shen L, Ostapenko Y, Bilici M, Chung HC, Shitara K, Qin SK, Van Cutsem E, Tabernero J, Li K, Shih CS, Bhagia P, Rha SY; KEYNOTE-811 Investigators. Pembrolizumab plus trastuzumab and chemotherapy for HER2-positive gastric or gastro-oesophageal junction adenocarcinoma: interim analyses from the phase 3 KEYNOTE-811 randomised placebo-controlled trial. Lancet. 2023 Dec 9;402(10418):2197-2208. Epub 2023 Oct 20. [https://doi.org/10.1016/s0140-6736(23)02033-0 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/37871604/ PubMed] | ||
+ | |||
=Metastatic or locally advanced disease, subsequent lines of therapy= | =Metastatic or locally advanced disease, subsequent lines of therapy= | ||
==Docetaxel monotherapy {{#subobject:4f3230|Regimen=1}}== | ==Docetaxel monotherapy {{#subobject:4f3230|Regimen=1}}== | ||
Line 308: | Line 408: | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
! style="width: 20%" |Study | ! style="width: 20%" |Study | ||
− | ! style="width: 20%" | | + | ! style="width: 20%" |Dates of enrollment |
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]] | ! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]] | ||
! style="width: 20%" |Comparator | ! style="width: 20%" |Comparator | ||
Line 314: | Line 414: | ||
|- | |- | ||
|[https://doi.org/10.1016/S1470-2045(17)30111-0 Thuss-Patience et al. 2017 (GATSBY)] | |[https://doi.org/10.1016/S1470-2045(17)30111-0 Thuss-Patience et al. 2017 (GATSBY)] | ||
− | |2012-2013 | + | |2012-09-03 to 2013-10-14 |
| style="background-color:#1a9851" |Phase 2/3 (C) | | style="background-color:#1a9851" |Phase 2/3 (C) | ||
− | |[[# | + | |[[#Trastuzumab_emtansine_monotherapy_999|T-DM1]] |
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS<br>Median OS: 8.6 vs 7.9 mo<br>(HR 0.87, 95% CI 0.66-1.15) | | style="background-color:#ffffbf" |Did not meet primary endpoint of OS<br>Median OS: 8.6 vs 7.9 mo<br>(HR 0.87, 95% CI 0.66-1.15) | ||
|- | |- | ||
Line 332: | Line 432: | ||
</div></div> | </div></div> | ||
===References=== | ===References=== | ||
− | #'''GATSBY:''' Thuss-Patience PC, Shah MA, Ohtsu A, Van Cutsem E, Ajani JA, Castro H, Mansoor W, Chung HC, Bodoky G, Shitara K, Phillips GDL, van der Horst T, Harle-Yge ML, Althaus BL, Kang YK. Trastuzumab emtansine versus taxane use for previously treated HER2-positive locally advanced or metastatic gastric or gastro-oesophageal junction adenocarcinoma (GATSBY): an international randomised, open-label, adaptive, phase 2/3 study. Lancet Oncol. 2017 May;18(5):640-653. Epub 2017 Mar 23. [https://doi.org/10.1016/S1470-2045(17)30111-0 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/28343975 PubMed] NCT01641939 | + | #'''GATSBY:''' Thuss-Patience PC, Shah MA, Ohtsu A, Van Cutsem E, Ajani JA, Castro H, Mansoor W, Chung HC, Bodoky G, Shitara K, Phillips GDL, van der Horst T, Harle-Yge ML, Althaus BL, Kang YK. Trastuzumab emtansine versus taxane use for previously treated HER2-positive locally advanced or metastatic gastric or gastro-oesophageal junction adenocarcinoma (GATSBY): an international randomised, open-label, adaptive, phase 2/3 study. Lancet Oncol. 2017 May;18(5):640-653. Epub 2017 Mar 23. [https://doi.org/10.1016/S1470-2045(17)30111-0 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/28343975/ PubMed] [https://clinicaltrials.gov/study/NCT01641939 NCT01641939] |
+ | |||
==Trastuzumab deruxtecan monotherapy {{#subobject:d2616v|Regimen=1}}== | ==Trastuzumab deruxtecan monotherapy {{#subobject:d2616v|Regimen=1}}== | ||
<div class="toccolours" style="background-color:#eeeeee"> | <div class="toccolours" style="background-color:#eeeeee"> | ||
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{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
! style="width: 20%" |Study | ! style="width: 20%" |Study | ||
− | ! style="width: 20%" | | + | ! style="width: 20%" |Dates of enrollment |
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]] | ! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]] | ||
! style="width: 20%" |Comparator | ! style="width: 20%" |Comparator | ||
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|- | |- | ||
|[https://doi.org/10.1056/nejmoa2004413 Shitara et al. 2020 (DESTINY-Gastric01)] | |[https://doi.org/10.1056/nejmoa2004413 Shitara et al. 2020 (DESTINY-Gastric01)] | ||
− | {| class="wikitable" style="margin:auto; color:white; background-color:#1B4F26" | + | <!-- {| class="wikitable" style="margin:auto; color:white; background-color:#1B4F26" |
|'''[https://www.esmo.org/guidelines/esmo-mcbs/esmo-mcbs-scorecards/scorecard-243-1 <span style="color:white;">ESMO-MCBS (4)</span>]''' | |'''[https://www.esmo.org/guidelines/esmo-mcbs/esmo-mcbs-scorecards/scorecard-243-1 <span style="color:white;">ESMO-MCBS (4)</span>]''' | ||
|- | |- | ||
− | |} | + | |} --> |
|2017-2019 | |2017-2019 | ||
| style="background-color:#1a9851" |Randomized Phase 2 (E-RT-switch-ooc) | | style="background-color:#1a9851" |Randomized Phase 2 (E-RT-switch-ooc) | ||
− | |Investigator's choice of:<br>1a. [[# | + | |Investigator's choice of:<br>1a. [[#Irinotecan_monotherapy|Irinotecan]]<br>1b. [[#Paclitaxel_monotherapy|Paclitaxel]] |
− | | style="background-color:#1a9850" |Superior OS (secondary endpoint)<br>Median OS: 12.5 vs 8.4 mo<br>(HR 0.59, 95% CI 0.39-0.88) | + | | style="background-color:#1a9850" |Superior OS (secondary endpoint)<br>Median OS: 12.5 vs 8.4 mo<br>(HR 0.59, 95% CI 0.39-0.88)<br><br>Superior ORR (primary endpoint) |
|- | |- | ||
|} | |} | ||
''Note: the dose is different from the FDA-approved dose for breast cancer.'' | ''Note: the dose is different from the FDA-approved dose for breast cancer.'' | ||
''Patients had received a median of two prior therapies for advanced or metastatic disease (17% had received at least four prior therapies, 72% had previously received ramucirumab and 86% had received taxanes).'' | ''Patients had received a median of two prior therapies for advanced or metastatic disease (17% had received at least four prior therapies, 72% had previously received ramucirumab and 86% had received taxanes).'' | ||
− | ''The median time since the last administration of trastuzumab was 5.9 months in the trastuzumab deruxtecan group and 6.5 months among those in the investigator's choice group.'' | + | ''The median time since the last administration of trastuzumab was 5.9 months in the trastuzumab deruxtecan group and 6.5 months among those in the investigator's choice group.'' |
<div class="toccolours" style="background-color:#fdcdac"> | <div class="toccolours" style="background-color:#fdcdac"> | ||
====Biomarker eligibility criteria==== | ====Biomarker eligibility criteria==== | ||
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'''21-day cycles''' | '''21-day cycles''' | ||
</div></div> | </div></div> | ||
+ | |||
===References=== | ===References=== | ||
− | #'''DESTINY-Gastric01:''' Shitara K, Bang YJ, Iwasa S, Sugimoto N, Ryu MH, Sakai D, Chung HC, Kawakami H, Yabusaki H, Lee J, Saito K, Kawaguchi Y, Kamio T, Kojima A, Sugihara M, Yamaguchi K; DESTINY-Gastric01 Investigators. Trastuzumab Deruxtecan in Previously Treated HER2-Positive Gastric Cancer. N Engl J Med. 2020 Jun 18;382(25):2419-2430. Epub 2020 May 29. [https://doi.org/10.1056/nejmoa2004413 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/32469182 PubMed] NCT03329690 | + | #'''DESTINY-Gastric01:''' Shitara K, Bang YJ, Iwasa S, Sugimoto N, Ryu MH, Sakai D, Chung HC, Kawakami H, Yabusaki H, Lee J, Saito K, Kawaguchi Y, Kamio T, Kojima A, Sugihara M, Yamaguchi K; DESTINY-Gastric01 Investigators. Trastuzumab Deruxtecan in Previously Treated HER2-Positive Gastric Cancer. N Engl J Med. 2020 Jun 18;382(25):2419-2430. Epub 2020 May 29. [https://doi.org/10.1056/nejmoa2004413 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/32469182/ PubMed] [https://clinicaltrials.gov/study/NCT03329690 NCT03329690] |
==Irinotecan monotherapy {{#subobject:6df2c0|Regimen=1}}== | ==Irinotecan monotherapy {{#subobject:6df2c0|Regimen=1}}== | ||
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{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
! style="width: 20%" |Study | ! style="width: 20%" |Study | ||
− | ! style="width: 20%" | | + | ! style="width: 20%" |Dates of enrollment |
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]] | ! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]] | ||
! style="width: 20%" |Comparator | ! style="width: 20%" |Comparator | ||
Line 396: | Line 498: | ||
</div></div> | </div></div> | ||
===References=== | ===References=== | ||
− | #'''DESTINY-Gastric01:''' Shitara K, Bang YJ, Iwasa S, Sugimoto N, Ryu MH, Sakai D, Chung HC, Kawakami H, Yabusaki H, Lee J, Saito K, Kawaguchi Y, Kamio T, Kojima A, Sugihara M, Yamaguchi K; DESTINY-Gastric01 Investigators. Trastuzumab Deruxtecan in Previously Treated HER2-Positive Gastric Cancer. N Engl J Med. 2020 Jun 18;382(25):2419-2430. Epub 2020 May 29. [https://doi.org/10.1056/nejmoa2004413 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/32469182 PubMed] NCT03329690 | + | #'''DESTINY-Gastric01:''' Shitara K, Bang YJ, Iwasa S, Sugimoto N, Ryu MH, Sakai D, Chung HC, Kawakami H, Yabusaki H, Lee J, Saito K, Kawaguchi Y, Kamio T, Kojima A, Sugihara M, Yamaguchi K; DESTINY-Gastric01 Investigators. Trastuzumab Deruxtecan in Previously Treated HER2-Positive Gastric Cancer. N Engl J Med. 2020 Jun 18;382(25):2419-2430. Epub 2020 May 29. [https://doi.org/10.1056/nejmoa2004413 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/32469182/ PubMed] [https://clinicaltrials.gov/study/NCT03329690 NCT03329690] |
==Paclitaxel monotherapy {{#subobject:2dcad9|Regimen=1}}== | ==Paclitaxel monotherapy {{#subobject:2dcad9|Regimen=1}}== | ||
<div class="toccolours" style="background-color:#eeeeee"> | <div class="toccolours" style="background-color:#eeeeee"> | ||
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{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
! style="width: 20%" |Study | ! style="width: 20%" |Study | ||
− | ! style="width: 20%" | | + | ! style="width: 20%" |Dates of enrollment |
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]] | ! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]] | ||
! style="width: 20%" |Comparator | ! style="width: 20%" |Comparator | ||
Line 408: | Line 510: | ||
|- | |- | ||
|[https://doi.org/10.1016/S1470-2045(17)30111-0 Thuss-Patience et al. 2017 (GATSBY)] | |[https://doi.org/10.1016/S1470-2045(17)30111-0 Thuss-Patience et al. 2017 (GATSBY)] | ||
− | |2012-2013 | + | |2012-09-03 to 2013-10-14 |
| style="background-color:#1a9851" |Phase 2/3 (C) | | style="background-color:#1a9851" |Phase 2/3 (C) | ||
− | |[[# | + | |[[#Trastuzumab_emtansine_monotherapy_999|T-DM1]] |
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS<br>Median OS: 8.6 vs 7.9 mo<br>(HR 0.87, 95% CI 0.66-1.15) | | style="background-color:#ffffbf" |Did not meet primary endpoint of OS<br>Median OS: 8.6 vs 7.9 mo<br>(HR 0.87, 95% CI 0.66-1.15) | ||
|- | |- | ||
Line 421: | Line 523: | ||
<div class="toccolours" style="background-color:#b3e2cd"> | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | *[[Paclitaxel (Taxol)]] 80 mg/m<sup>2</sup> IV once | + | *[[Paclitaxel (Taxol)]] 80 mg/m<sup>2</sup> IV once on day 1 |
− | ''' | + | '''7-day cycles''' |
</div></div><br> | </div></div><br> | ||
<div class="toccolours" style="background-color:#eeeeee"> | <div class="toccolours" style="background-color:#eeeeee"> | ||
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{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
! style="width: 20%" |Study | ! style="width: 20%" |Study | ||
− | ! style="width: 20%" | | + | ! style="width: 20%" |Dates of enrollment |
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]] | ! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]] | ||
! style="width: 20%" |Comparator | ! style="width: 20%" |Comparator | ||
Line 436: | Line 538: | ||
|2007-2009 | |2007-2009 | ||
| style="background-color:#1a9851" |Phase 3 (C) | | style="background-color:#1a9851" |Phase 3 (C) | ||
− | |[[#Lapatinib_. | + | |[[#Lapatinib_.26_Paclitaxel_999|Lapatinib & Paclitaxel]] |
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS<br>Median OS: 8.9 vs 11 mo<br>(HR 1.19, 95% CI 0.90-1.56) | | style="background-color:#ffffbf" |Did not meet primary endpoint of OS<br>Median OS: 8.9 vs 11 mo<br>(HR 1.19, 95% CI 0.90-1.56) | ||
|- | |- | ||
Line 456: | Line 558: | ||
</div></div> | </div></div> | ||
===References=== | ===References=== | ||
− | #'''TyTAN:''' Satoh T, Xu RH, Chung HC, Sun GP, Doi T, Xu JM, Tsuji A, Omuro Y, Li J, Wang JW, Miwa H, Qin SK, Chung IJ, Yeh KH, Feng JF, Mukaiyama A, Kobayashi M, Ohtsu A, Bang YJ. Lapatinib plus paclitaxel versus paclitaxel alone in the second-line treatment of HER2-amplified advanced gastric cancer in Asian populations: TyTAN--a randomized, phase III study. J Clin Oncol. 2014 Jul 1;32(19):2039-49. Epub 2014 May 27. [https://doi.org/10.1200/JCO.2013.53.6136 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/24868024 PubMed] NCT00486954 | + | #'''TyTAN:''' Satoh T, Xu RH, Chung HC, Sun GP, Doi T, Xu JM, Tsuji A, Omuro Y, Li J, Wang JW, Miwa H, Qin SK, Chung IJ, Yeh KH, Feng JF, Mukaiyama A, Kobayashi M, Ohtsu A, Bang YJ. Lapatinib plus paclitaxel versus paclitaxel alone in the second-line treatment of HER2-amplified advanced gastric cancer in Asian populations: TyTAN--a randomized, phase III study. J Clin Oncol. 2014 Jul 1;32(19):2039-49. Epub 2014 May 27. [https://doi.org/10.1200/JCO.2013.53.6136 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/24868024/ PubMed] [https://clinicaltrials.gov/study/NCT00486954 NCT00486954] |
− | #'''GATSBY:''' Thuss-Patience PC, Shah MA, Ohtsu A, Van Cutsem E, Ajani JA, Castro H, Mansoor W, Chung HC, Bodoky G, Shitara K, Phillips GDL, van der Horst T, Harle-Yge ML, Althaus BL, Kang YK. Trastuzumab emtansine versus taxane use for previously treated HER2-positive locally advanced or metastatic gastric or gastro-oesophageal junction adenocarcinoma (GATSBY): an international randomised, open-label, adaptive, phase 2/3 study. Lancet Oncol. 2017 May;18(5):640-653. Epub 2017 Mar 23. [https://doi.org/10.1016/S1470-2045(17)30111-0 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/28343975 PubMed] NCT01641939 | + | #'''GATSBY:''' Thuss-Patience PC, Shah MA, Ohtsu A, Van Cutsem E, Ajani JA, Castro H, Mansoor W, Chung HC, Bodoky G, Shitara K, Phillips GDL, van der Horst T, Harle-Yge ML, Althaus BL, Kang YK. Trastuzumab emtansine versus taxane use for previously treated HER2-positive locally advanced or metastatic gastric or gastro-oesophageal junction adenocarcinoma (GATSBY): an international randomised, open-label, adaptive, phase 2/3 study. Lancet Oncol. 2017 May;18(5):640-653. Epub 2017 Mar 23. [https://doi.org/10.1016/S1470-2045(17)30111-0 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/28343975/ PubMed] [https://clinicaltrials.gov/study/NCT01641939 NCT01641939] |
− | #'''DESTINY-Gastric01:''' Shitara K, Bang YJ, Iwasa S, Sugimoto N, Ryu MH, Sakai D, Chung HC, Kawakami H, Yabusaki H, Lee J, Saito K, Kawaguchi Y, Kamio T, Kojima A, Sugihara M, Yamaguchi K; DESTINY-Gastric01 Investigators. Trastuzumab Deruxtecan in Previously Treated HER2-Positive Gastric Cancer. N Engl J Med. 2020 Jun 18;382(25):2419-2430. Epub 2020 May 29. [https://doi.org/10.1056/nejmoa2004413 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/32469182 PubMed] NCT03329690 | + | #'''DESTINY-Gastric01:''' Shitara K, Bang YJ, Iwasa S, Sugimoto N, Ryu MH, Sakai D, Chung HC, Kawakami H, Yabusaki H, Lee J, Saito K, Kawaguchi Y, Kamio T, Kojima A, Sugihara M, Yamaguchi K; DESTINY-Gastric01 Investigators. Trastuzumab Deruxtecan in Previously Treated HER2-Positive Gastric Cancer. N Engl J Med. 2020 Jun 18;382(25):2419-2430. Epub 2020 May 29. [https://doi.org/10.1056/nejmoa2004413 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/32469182/ PubMed] [https://clinicaltrials.gov/study/NCT03329690 NCT03329690] |
==Paclitaxel & Ramucirumab {{#subobject:fdd93f|Regimen=1}}== | ==Paclitaxel & Ramucirumab {{#subobject:fdd93f|Regimen=1}}== | ||
<div class="toccolours" style="background-color:#eeeeee"> | <div class="toccolours" style="background-color:#eeeeee"> | ||
Line 464: | Line 566: | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
! style="width: 20%" |Study | ! style="width: 20%" |Study | ||
− | ! style="width: 20%" | | + | ! style="width: 20%" |Dates of enrollment |
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]] | ! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]] | ||
! style="width: 20%" |Comparator | ! style="width: 20%" |Comparator | ||
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
|- | |- | ||
− | |[https://www.clinicaltrials.gov/ | + | |[https://www.clinicaltrials.gov/study/NCT04704934 Awaiting publication (DESTINY-Gastric04)] |
|2021-ongoing | |2021-ongoing | ||
| style="background-color:#1a9851" |Phase 3 (C) | | style="background-color:#1a9851" |Phase 3 (C) | ||
Line 485: | Line 587: | ||
</div></div> | </div></div> | ||
===References=== | ===References=== | ||
− | #'''DESTINY-Gastric04:''' NCT04704934 | + | #'''DESTINY-Gastric04:''' [https://clinicaltrials.gov/study/NCT04704934 NCT04704934] |
[[Category:Gastric cancer regimens]] | [[Category:Gastric cancer regimens]] | ||
[[Category:Biomarker-specific pages]] | [[Category:Biomarker-specific pages]] | ||
[[Category:Gastroesophageal cancers]] | [[Category:Gastroesophageal cancers]] |
Latest revision as of 00:28, 4 July 2024
Section editor | |
---|---|
Travis Zack, MD, PhD University of California San Francisco San Francisco, CA, USA |
Note: these are regimens tested in biomarker-specific populations and includes gastric and gastroesophageal cancers. Please see the main gastric cancer page or the main esophageal cancer page for other regimens.
14 regimens on this page
15 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.
CAP/ASCP/ASCO
- 2017: Bartley et al. HER2 testing and clinical decision making in gastroesophageal adenocarcinoma PubMed
NCCN
- NCCN does not currently have guidelines at this granular level; please see NCCN Guidelines - Esophageal and Esophagogastric Junction Cancers and NCCN Guidelines - Gastric Cancer.
Metastatic or locally advanced disease, first-line
Capecitabine & Cisplatin (CX)
CX: Cisplatin & Xeloda (Capecitabine)
XP: Xeloda (Capecitabine) & Platinol (Cisplatin)
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Bang et al. 2010 (ToGA) | 2005-2008 | Phase 3 (C-RT) | 1a. CF & Trastuzumab 1b. CX & Trastuzumab |
Inferior OS |
Patients:100% adenocarcinoma (19% gastroesophageal junction, 81% gastric). 10% with ECOG of 2.
Biomarker eligibility criteria
- Overexpression of HER2 protein by immunohistochemistry or gene amplification by fluorescence in-situ hybridisation
Chemotherapy
- Cisplatin (Platinol) 80 mg/m2 IV over 2 hours once on day 1
- Capecitabine (Xeloda) 1000 mg/m2 PO twice per day on days 1 to 14
21-day cycles
References
- ToGA: Bang YJ, Van Cutsem E, Feyereislova A, Chung HC, Shen L, Sawaki A, Lordick F, Ohtsu A, Omuro Y, Satoh T, Aprile G, Kulikov E, Hill J, Lehle M, Rüschoff J, Kang YK; ToGA Trial Investigators. Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer (ToGA): a phase 3, open-label, randomised controlled trial. Lancet. 2010 Aug 28;376(9742):687-97. Epub 2010 Aug 19. link to original article contains dosing details in manuscript PubMed NCT01041404
Capecitabine & Cisplatin (CX) & Trastuzumab
CX & Trastuzumab: Cisplatin, Xeloda (Capecitabine), Trastuzumab
Regimen variant #1, 80/1600
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Shah et al. 2017 (HELOISE) | 2011-2015 | Phase 3b (C) | CX & Trastuzumab; high-dose | Did not meet primary endpoint of OS |
Patients: 79% gastric, 21% GE junction, and all patients had an ECOG of 2
Biomarker eligibility criteria
Patients had overexpression of HER2 protein by immunohistochemistry AND gene amplification by in-situ hybridization.
Chemotherapy
- Cisplatin (Platinol) as follows:
- Cycles 1 to 6: 80 mg/m2 IV once on day 1
- Capecitabine (Xeloda) as follows:
- Cycles 1 to 6: 800 mg/m2 PO twice per day on days 1 to 14
Targeted therapy
- Trastuzumab (Herceptin) as follows:
- Cycle 1: 8 mg/kg IV once on day 1
- Cycles 2 to 6: 6 mg/kg IV once on day 1
- Cycle 7 onwards: 10 mg/kg IV once on day 1
21-day cycles
Regimen variant #2, 80/2000
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Bang et al. 2010 (ToGA) | 2005-2008 | Phase 3 (E-RT-esc) | 1a. CF 1b. CX |
Superior OS (primary endpoint) Median OS: 13.8 vs 11.1 mo (HR 0.74, 95% CI 0.60-0.91) |
Tabernero et al. 2018 (JACOB) | 2013-2016 | Phase 3 (C) | CX, Pertuzumab, Trastuzumab | Seems to have inferior OS1 Median OS: 14.2 vs 18.1 mo (HR 1.18, 95% CI 1.01-1.39) |
1Reported efficacy is based on the 2022 update.
ToGA patients: 81% gastric, 19% GE junction. 10% of patients with ECOG of 2.
Biomarker eligibility criteria
- ToGA: overexpression of HER2 protein by immunohistochemistry OR gene amplification by fluorescence in-situ hybridization.
Chemotherapy
- Cisplatin (Platinol) 80 mg/m2 IV once on day 1
- Capecitabine (Xeloda) 1000 mg/m2 PO twice per day on days 1 to 14
Targeted therapy
- Trastuzumab (Herceptin) as follows:
- Cycle 1: 8 mg/kg IV once on day 1
- Cycle 2 onwards: 6 mg/kg IV once on day 1
21-day cycles
References
- ToGA: Bang YJ, Van Cutsem E, Feyereislova A, Chung HC, Shen L, Sawaki A, Lordick F, Ohtsu A, Omuro Y, Satoh T, Aprile G, Kulikov E, Hill J, Lehle M, Rüschoff J, Kang YK; ToGA Trial Investigators. Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer (ToGA): a phase 3, open-label, randomised controlled trial. Lancet. 2010 Aug 28;376(9742):687-97. Epub 2010 Aug 19. link to original article contains dosing details in manuscript PubMed NCT01041404
- HELOISE: Shah MA, Xu RH, Bang YJ, Hoff PM, Liu T, Herráez-Baranda LA, Xia F, Garg A, Shing M, Tabernero J. HELOISE: Phase IIIb randomized multicenter study comparing standard-of-care and higher-dose trastuzumab regimens combined with chemotherapy as first-line therapy in patients with human epidermal growth factor receptor 2-positive metastatic gastric or gastroesophageal junction adenocarcinoma. J Clin Oncol. 2017 Aug 1;35(22):2558-2567. Epub 2017 Jun 2. link to original article contains dosing details in manuscript PubMed NCT01450696
- JACOB: Tabernero J, Hoff PM, Shen L, Ohtsu A, Shah MA, Cheng K, Song C, Wu H, Eng-Wong J, Kim K, Kang YK. Pertuzumab plus trastuzumab and chemotherapy for HER2-positive metastatic gastric or gastro-oesophageal junction cancer (JACOB): final analysis of a double-blind, randomised, placebo-controlled phase 3 study. Lancet Oncol. 2018 Oct;19(10):1372-1384. Epub 2018 Sep 11. link to original article contains dosing details in abstract PubMed NCT01774786
- Update: Tabernero J, Hoff PM, Shen L, Ohtsu A, Shah MA, Siddiqui A, Heeson S, Kiermaier A, Macharia H, Restuccia E, Kang YK. Pertuzumab, trastuzumab, and chemotherapy in HER2-positive gastric/gastroesophageal junction cancer: end-of-study analysis of the JACOB phase III randomized clinical trial. Gastric Cancer. 2023 Jan;26(1):123-131. Epub 2022 Sep 6. link to original article link to PMC article PubMed
Capecitabine & Cisplatin (CX), Pertuzumab, Trastuzumab
CX, Pertuzumab, Trastuzumab: Cisplatin, Xeloda (Capecitabine), Pertuzumab, Trastuzumab
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Tabernero et al. 2018 (JACOB) | 2013-2016 | Phase 3 (E-esc) | CX & Trastuzumab | Seems to have superior OS1 (primary endpoint) Median OS: 18.1 vs 14.2 mo (HR 0.85, 95% CI 0.72-0.99) |
1Reported efficacy is based on the 2022 update.
Chemotherapy
- Cisplatin (Platinol) 80 mg/m2 IV once on day 1
- Capecitabine (Xeloda) 1000 mg/m2 PO twice per day on days 1 to 14
Targeted therapy
- Pertuzumab (Perjeta) 840 mg IV once on day 1
- Trastuzumab (Herceptin) as follows:
- Cycle 1: 8 mg/kg IV once on day 1
- Cycle 2 onwards: 6 mg/kg IV once on day 1
21-day cycles
References
- JACOB: Tabernero J, Hoff PM, Shen L, Ohtsu A, Shah MA, Cheng K, Song C, Wu H, Eng-Wong J, Kim K, Kang YK. Pertuzumab plus trastuzumab and chemotherapy for HER2-positive metastatic gastric or gastro-oesophageal junction cancer (JACOB): final analysis of a double-blind, randomised, placebo-controlled phase 3 study. Lancet Oncol. 2018 Oct;19(10):1372-1384. Epub 2018 Sep 11. link to original article contains dosing details in abstract PubMed NCT01774786
- Update: Tabernero J, Hoff PM, Shen L, Ohtsu A, Shah MA, Siddiqui A, Heeson S, Kiermaier A, Macharia H, Restuccia E, Kang YK. Pertuzumab, trastuzumab, and chemotherapy in HER2-positive gastric/gastroesophageal junction cancer: end-of-study analysis of the JACOB phase III randomized clinical trial. Gastric Cancer. 2023 Jan;26(1):123-131. Epub 2022 Sep 6. link to original article link to PMC article PubMed
CapeOx
CapeOx: Capecitabine and Oxaliplatin
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Hecht et al. 2015 (LOGiC) | 2008-2012 | Phase 3 (C) | CapeOx & Lapatinib | Did not meet primary endpoint of OS Median OS: 10.5 vs 12.2 mo (HR 1.10, 95% CI 0.89-1.37) |
100% adenocarcinoma histology (4% esophagus, 9% gastroesophageal junction, 87% gastric origin). 9% with ECOG PS of 2.
Biomarker eligibility criteria
- HER2 positive
Chemotherapy
- Capecitabine (Xeloda) 850 mg/m2 PO twice per day on days 1 to 14
- Oxaliplatin (Eloxatin) 130 mg/m2 IV once on day 1
21-day cycle for up to 8 cycles
References
- LOGiC: Hecht JR, Bang YJ, Qin SK, Chung HC, Xu JM, Park JO, Jeziorski K, Shparyk Y, Hoff PM, Sobrero A, Salman P, Li J, Protsenko SA, Wainberg ZA, Buyse M, Afenjar K, Houé V, Garcia A, Kaneko T, Huang Y, Khan-Wasti S, Santillana S, Press MF, Slamon D. Lapatinib in combination with capecitabine plus oxaliplatin in human epidermal growth factor receptor 2-positive advanced or metastatic gastric, esophageal, or gastroesophageal adenocarcinoma: TRIO-013/LOGiC--a randomized phase III trial. J Clin Oncol. 2016 Feb 10;34(5):443-51. Epub 2015 Nov 30. link to original article PubMed NCT00680901
- HERIZON-GEA-01: NCT05152147
CapeOx, Pembrolizumab, Trastuzumab
CapeOx, Pembrolizumab, Trastuzumab: Capecitabine, Oxaliplatin, Pembrolizumab, Trastuzumab
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Janjigian et al. 2021 (KEYNOTE-811) | 2018-2020 | Phase 3 (E-RT-esc) | 1a. CapeOx & Trastuzumab 1b. CF & Trastuzumab |
Superior PFS1 (co-primary endpoint) Median PFS: 10 vs 8.1 mo (HR 0.73, 95% CI 0.61-0.87) Might have superior OS1 (co-primary endpoint) Median OS: 20 vs 16.8 mo (HR 0.84, 95% CI 0.70-1.01) |
1Reported efficacy is based on the 2023 update.
Biomarker eligibility criteria
- HER2 positive
Chemotherapy
- Capecitabine (Xeloda) 1000 mg/m2 PO twice per day on days 1 to 14
- Oxaliplatin (Eloxatin) 130 mg/m2 IV over 2 hours once on day 1
Immunotherapy
- Pembrolizumab (Keytruda) 200 mg IV once on day 1
Targeted therapy
- Trastuzumab (Herceptin) as follows:
- Cycle 1: 8 mg/kg IV once on day 1
- Cycle 2 onwards: 6 mg/kg IV once on day 1
21-day cycle for up to 35 cycles (2 years)
References
- KEYNOTE-811: Janjigian YY, Kawazoe A, Yañez P, Li N, Lonardi S, Kolesnik O, Barajas O, Bai Y, Shen L, Tang Y, Wyrwicz LS, Xu J, Shitara K, Qin S, Van Cutsem E, Tabernero J, Li L, Shah S, Bhagia P, Chung HC. The KEYNOTE-811 trial of dual PD-1 and HER2 blockade in HER2-positive gastric cancer. Nature. 2021 Dec;600(7890):727-730. Epub 2021 Dec 15. link to original article link to PMC article contains dosing details in manuscript PubMed NCT03615326
- Update: Janjigian YY, Kawazoe A, Bai Y, Xu J, Lonardi S, Metges JP, Yanez P, Wyrwicz LS, Shen L, Ostapenko Y, Bilici M, Chung HC, Shitara K, Qin SK, Van Cutsem E, Tabernero J, Li K, Shih CS, Bhagia P, Rha SY; KEYNOTE-811 Investigators. Pembrolizumab plus trastuzumab and chemotherapy for HER2-positive gastric or gastro-oesophageal junction adenocarcinoma: interim analyses from the phase 3 KEYNOTE-811 randomised placebo-controlled trial. Lancet. 2023 Dec 9;402(10418):2197-2208. Epub 2023 Oct 20. link to original article PubMed
CapeOx & Trastuzumab
CapeOx & Trastuzumab: Capecitabine, Oxaliplatin, Trastuzumab
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Janjigian et al. 2021 (KEYNOTE-811) | 2018-2020 | Phase 3 (C) | 1a. CapeOx, Pembrolizumab, Trastuzumab 1b. CF, Pembrolizumab, Trastuzumab |
Inferior PFS1 Might have inferior OS1 |
1Reported efficacy is based on the 2023 update.
Note: to our knowledge, this regimen was not tested as an experimental arm in an RCT in this context, prior to becoming a standard comparator arm.
Biomarker eligibility criteria
- HER2 positive
Chemotherapy
- Capecitabine (Xeloda) 1000 mg/m2 PO twice per day on days 1 to 14
- Oxaliplatin (Eloxatin) 130 mg/m2 IV over 2 hours once on day 1
Targeted therapy
- Trastuzumab (Herceptin) as follows:
- Cycle 1: 8 mg/kg IV once on day 1
- Cycle 2 onwards: 6 mg/kg IV once on day 1
21-day cycles
References
- KEYNOTE-811: Janjigian YY, Kawazoe A, Yañez P, Li N, Lonardi S, Kolesnik O, Barajas O, Bai Y, Shen L, Tang Y, Wyrwicz LS, Xu J, Shitara K, Qin S, Van Cutsem E, Tabernero J, Li L, Shah S, Bhagia P, Chung HC. The KEYNOTE-811 trial of dual PD-1 and HER2 blockade in HER2-positive gastric cancer. Nature. 2021 Dec;600(7890):727-730. Epub 2021 Dec 15. link to original article link to PMC article contains dosing details in manuscript PubMed NCT03615326
- Update: Janjigian YY, Kawazoe A, Bai Y, Xu J, Lonardi S, Metges JP, Yanez P, Wyrwicz LS, Shen L, Ostapenko Y, Bilici M, Chung HC, Shitara K, Qin SK, Van Cutsem E, Tabernero J, Li K, Shih CS, Bhagia P, Rha SY; KEYNOTE-811 Investigators. Pembrolizumab plus trastuzumab and chemotherapy for HER2-positive gastric or gastro-oesophageal junction adenocarcinoma: interim analyses from the phase 3 KEYNOTE-811 randomised placebo-controlled trial. Lancet. 2023 Dec 9;402(10418):2197-2208. Epub 2023 Oct 20. link to original article PubMed
Cisplatin & Fluorouracil (CF)
CF: Cisplatin & Fluorouracil
FP: Fluorouracil & Platinol (Cisplatin)
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Bang et al. 2010 (ToGA) | 2005-2008 | Phase 3 (C) | 1a. CF & Trastuzumab 1b. CX & Trastuzumab |
Inferior OS |
ToGA Patients: 100% adenocarcinoma (19% gastroesophageal junction, 81% gastric). 10% with ECOG of 2.
Biomarker eligibility criteria
- Overexpression of HER2 protein by immunohistochemistry or gene amplification by fluorescence in-situ hybridisation.
Chemotherapy
- Cisplatin (Platinol) 80 mg/m2 IV over 1 to 3 hours once on day 1, given first
- Fluorouracil (5-FU) 800 mg/m2/day IV continuous infusion over 120 hours, started on day 1, given second (total dose per cycle: 4000 mg/m2)
21-day cycle for up to 6 cycles
References
- ToGA: Bang YJ, Van Cutsem E, Feyereislova A, Chung HC, Shen L, Sawaki A, Lordick F, Ohtsu A, Omuro Y, Satoh T, Aprile G, Kulikov E, Hill J, Lehle M, Rüschoff J, Kang YK; ToGA Trial Investigators. Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer (ToGA): a phase 3, open-label, randomised controlled trial. Lancet. 2010 Aug 28;376(9742):687-97. Epub 2010 Aug 19. link to original article contains dosing details in manuscript PubMed NCT01041404
Cisplatin & Fluorouracil (CF) & Trastuzumab
CF & Trastuzumab: Cisplatin, Fluorouracil, Trastuzumab
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Bang et al. 2010 (ToGA) | 2005-2008 | Phase 3 (E-RT-esc) | 1a. CF 1b. CX |
Superior OS (primary endpoint) Median OS: 13.8 vs 11.1 mo (HR 0.74, 95% CI 0.60-0.91) |
Janjigian et al. 2021 (KEYNOTE-811) | 2018-2020 | Phase 3 (C) | 1a. CapeOx, Pembrolizumab, Trastuzumab 1b. CF, Pembrolizumab, Trastuzumab |
Inferior PFS1 Might have inferior OS1 |
1Reported efficacy is based on the 2023 update.
Patients: 100% adenocarcinoma (19% gastroesophageal junction, 81% gastric). 10% with ECOG of 2.
Biomarker eligibility criteria
- Patients had overexpression of HER2 protein by immunohistochemistry or gene amplification by fluorescence in-situ hybridisation.
Chemotherapy
- Cisplatin (Platinol) 80 mg/m2 IV once on day 1
- Fluorouracil (5-FU) 800 mg/m2/day IV continuous infusion over 120 hours, started on day 1 (total dose per cycle: 4000 mg/m2)
Targeted therapy
- Trastuzumab (Herceptin) as follows:
- Cycle 1: 8 mg/kg IV once on day 1
- Cycle 2 onwards: 6 mg/kg IV once on day 1
21-day cycles
References
- ToGA: Bang YJ, Van Cutsem E, Feyereislova A, Chung HC, Shen L, Sawaki A, Lordick F, Ohtsu A, Omuro Y, Satoh T, Aprile G, Kulikov E, Hill J, Lehle M, Rüschoff J, Kang YK; ToGA Trial Investigators. Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer (ToGA): a phase 3, open-label, randomised controlled trial. Lancet. 2010 Aug 28;376(9742):687-97. Epub 2010 Aug 19. link to original article contains dosing details in manuscript PubMed NCT01041404
- KEYNOTE-811: Janjigian YY, Kawazoe A, Yañez P, Li N, Lonardi S, Kolesnik O, Barajas O, Bai Y, Shen L, Tang Y, Wyrwicz LS, Xu J, Shitara K, Qin S, Van Cutsem E, Tabernero J, Li L, Shah S, Bhagia P, Chung HC. The KEYNOTE-811 trial of dual PD-1 and HER2 blockade in HER2-positive gastric cancer. Nature. 2021 Dec;600(7890):727-730. Epub 2021 Dec 15. link to original article link to PMC article PubMed NCT03615326
- Update: Janjigian YY, Kawazoe A, Bai Y, Xu J, Lonardi S, Metges JP, Yanez P, Wyrwicz LS, Shen L, Ostapenko Y, Bilici M, Chung HC, Shitara K, Qin SK, Van Cutsem E, Tabernero J, Li K, Shih CS, Bhagia P, Rha SY; KEYNOTE-811 Investigators. Pembrolizumab plus trastuzumab and chemotherapy for HER2-positive gastric or gastro-oesophageal junction adenocarcinoma: interim analyses from the phase 3 KEYNOTE-811 randomised placebo-controlled trial. Lancet. 2023 Dec 9;402(10418):2197-2208. Epub 2023 Oct 20. link to original article contains dosing details in manuscript PubMed
- HERIZON-GEA-01: NCT05152147
Cisplatin & Fluorouracil (CF), Pembrolizumab, Trastuzumab
CF, Pembrolizumab, Trastuzumab: Cisplatin, Fluorouracil, Pembrolizumab, Trastuzumab
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Janjigian et al. 2021 (KEYNOTE-811) | 2018-2020 | Phase 3 (E-RT-esc) | 1a. CapeOx & Trastuzumab 1b. CF & Trastuzumab |
Superior PFS1 (co-primary endpoint) Median PFS: 10 vs 8.1 mo (HR 0.73, 95% CI 0.61-0.87) Might have superior OS1 (co-primary endpoint) Median OS: 20 vs 16.8 mo (HR 0.84, 95% CI 0.70-1.01) |
1Reported efficacy is based on the 2023 update.
Biomarker eligibility criteria
- HER2 positive
Chemotherapy
- Cisplatin (Platinol) 80 mg/m2 IV once on day 1
- Fluorouracil (5-FU) 800 mg/m2/day IV continuous infusion over 120 hours, started on day 1 (total dose per cycle: 4000 mg/m2)
Immunotherapy
- Pembrolizumab (Keytruda) 200 mg IV once on day 1
Targeted therapy
- Trastuzumab (Herceptin) as follows:
- Cycle 1: 8 mg/kg IV once on day 1
- Cycle 2 onwards: 6 mg/kg IV once on day 1
21-day cycles
References
- KEYNOTE-811: Janjigian YY, Kawazoe A, Yañez P, Li N, Lonardi S, Kolesnik O, Barajas O, Bai Y, Shen L, Tang Y, Wyrwicz LS, Xu J, Shitara K, Qin S, Van Cutsem E, Tabernero J, Li L, Shah S, Bhagia P, Chung HC. The KEYNOTE-811 trial of dual PD-1 and HER2 blockade in HER2-positive gastric cancer. Nature. 2021 Dec;600(7890):727-730. Epub 2021 Dec 15. link to original article link to PMC article PubMed NCT03615326
- Update: Janjigian YY, Kawazoe A, Bai Y, Xu J, Lonardi S, Metges JP, Yanez P, Wyrwicz LS, Shen L, Ostapenko Y, Bilici M, Chung HC, Shitara K, Qin SK, Van Cutsem E, Tabernero J, Li K, Shih CS, Bhagia P, Rha SY; KEYNOTE-811 Investigators. Pembrolizumab plus trastuzumab and chemotherapy for HER2-positive gastric or gastro-oesophageal junction adenocarcinoma: interim analyses from the phase 3 KEYNOTE-811 randomised placebo-controlled trial. Lancet. 2023 Dec 9;402(10418):2197-2208. Epub 2023 Oct 20. link to original article contains dosing details in manuscript PubMed
Metastatic or locally advanced disease, subsequent lines of therapy
Docetaxel monotherapy
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Thuss-Patience et al. 2017 (GATSBY) | 2012-09-03 to 2013-10-14 | Phase 2/3 (C) | T-DM1 | Did not meet primary endpoint of OS Median OS: 8.6 vs 7.9 mo (HR 0.87, 95% CI 0.66-1.15) |
Note: study patients could only have been treated by one other regimen and could not have been exposed to anthracyclines Patients: 68% gastric, 32% GEJ
Biomarker eligibility criteria
- HER2-positive disease
References
- GATSBY: Thuss-Patience PC, Shah MA, Ohtsu A, Van Cutsem E, Ajani JA, Castro H, Mansoor W, Chung HC, Bodoky G, Shitara K, Phillips GDL, van der Horst T, Harle-Yge ML, Althaus BL, Kang YK. Trastuzumab emtansine versus taxane use for previously treated HER2-positive locally advanced or metastatic gastric or gastro-oesophageal junction adenocarcinoma (GATSBY): an international randomised, open-label, adaptive, phase 2/3 study. Lancet Oncol. 2017 May;18(5):640-653. Epub 2017 Mar 23. link to original article contains dosing details in abstract PubMed NCT01641939
Trastuzumab deruxtecan monotherapy
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Shitara et al. 2020 (DESTINY-Gastric01) | 2017-2019 | Randomized Phase 2 (E-RT-switch-ooc) | Investigator's choice of: 1a. Irinotecan 1b. Paclitaxel |
Superior OS (secondary endpoint) Median OS: 12.5 vs 8.4 mo (HR 0.59, 95% CI 0.39-0.88) Superior ORR (primary endpoint) |
Note: the dose is different from the FDA-approved dose for breast cancer. Patients had received a median of two prior therapies for advanced or metastatic disease (17% had received at least four prior therapies, 72% had previously received ramucirumab and 86% had received taxanes). The median time since the last administration of trastuzumab was 5.9 months in the trastuzumab deruxtecan group and 6.5 months among those in the investigator's choice group.
Biomarker eligibility criteria
- HER2 over-expression
Antibody-drug conjugate therapy
- Trastuzumab deruxtecan (Enhertu) 6.4 mg/kg IV once on day 1
21-day cycles
References
- DESTINY-Gastric01: Shitara K, Bang YJ, Iwasa S, Sugimoto N, Ryu MH, Sakai D, Chung HC, Kawakami H, Yabusaki H, Lee J, Saito K, Kawaguchi Y, Kamio T, Kojima A, Sugihara M, Yamaguchi K; DESTINY-Gastric01 Investigators. Trastuzumab Deruxtecan in Previously Treated HER2-Positive Gastric Cancer. N Engl J Med. 2020 Jun 18;382(25):2419-2430. Epub 2020 May 29. link to original article contains dosing details in manuscript PubMed NCT03329690
Irinotecan monotherapy
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Shitara et al. 2020 (DESTINY-Gastric01) | 2017-2019 | Randomized Phase 2 (C) | Trastuzumab deruxtecan | Inferior OS |
Biomarker eligibility criteria
- DESTINY-Gastric01: HER2 over-expression
References
- DESTINY-Gastric01: Shitara K, Bang YJ, Iwasa S, Sugimoto N, Ryu MH, Sakai D, Chung HC, Kawakami H, Yabusaki H, Lee J, Saito K, Kawaguchi Y, Kamio T, Kojima A, Sugihara M, Yamaguchi K; DESTINY-Gastric01 Investigators. Trastuzumab Deruxtecan in Previously Treated HER2-Positive Gastric Cancer. N Engl J Med. 2020 Jun 18;382(25):2419-2430. Epub 2020 May 29. link to original article contains dosing details in manuscript PubMed NCT03329690
Paclitaxel monotherapy
Regimen variant #1, 80 mg/m2 weekly
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Thuss-Patience et al. 2017 (GATSBY) | 2012-09-03 to 2013-10-14 | Phase 2/3 (C) | T-DM1 | Did not meet primary endpoint of OS Median OS: 8.6 vs 7.9 mo (HR 0.87, 95% CI 0.66-1.15) |
GATSBY included patients with GE junction malignancy (68% gastric, 32% GE junction)
Biomarker eligibility criteria
- Overexpression of HER2 protein by immunohistochemistry or gene amplification by fluorescence in-situ hybridisation
Regimen variant #2, 80 mg/m2, 3 out of 4 weeks
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Satoh et al. 2014 (TyTAN) | 2007-2009 | Phase 3 (C) | Lapatinib & Paclitaxel | Did not meet primary endpoint of OS Median OS: 8.9 vs 11 mo (HR 1.19, 95% CI 0.90-1.56) |
Shitara et al. 2020 (DESTINY-Gastric01) | 2017-2019 | Randomized Phase 2 (C) | Trastuzumab deruxtecan | Inferior OS |
Biomarker eligibility criteria
- HER2-positive disease
Chemotherapy
- Paclitaxel (Taxol) 80 mg/m2 IV over 60 minutes once per day on days 1, 8, 15
28-day cycles
References
- TyTAN: Satoh T, Xu RH, Chung HC, Sun GP, Doi T, Xu JM, Tsuji A, Omuro Y, Li J, Wang JW, Miwa H, Qin SK, Chung IJ, Yeh KH, Feng JF, Mukaiyama A, Kobayashi M, Ohtsu A, Bang YJ. Lapatinib plus paclitaxel versus paclitaxel alone in the second-line treatment of HER2-amplified advanced gastric cancer in Asian populations: TyTAN--a randomized, phase III study. J Clin Oncol. 2014 Jul 1;32(19):2039-49. Epub 2014 May 27. link to original article contains dosing details in manuscript PubMed NCT00486954
- GATSBY: Thuss-Patience PC, Shah MA, Ohtsu A, Van Cutsem E, Ajani JA, Castro H, Mansoor W, Chung HC, Bodoky G, Shitara K, Phillips GDL, van der Horst T, Harle-Yge ML, Althaus BL, Kang YK. Trastuzumab emtansine versus taxane use for previously treated HER2-positive locally advanced or metastatic gastric or gastro-oesophageal junction adenocarcinoma (GATSBY): an international randomised, open-label, adaptive, phase 2/3 study. Lancet Oncol. 2017 May;18(5):640-653. Epub 2017 Mar 23. link to original article contains dosing details in abstract PubMed NCT01641939
- DESTINY-Gastric01: Shitara K, Bang YJ, Iwasa S, Sugimoto N, Ryu MH, Sakai D, Chung HC, Kawakami H, Yabusaki H, Lee J, Saito K, Kawaguchi Y, Kamio T, Kojima A, Sugihara M, Yamaguchi K; DESTINY-Gastric01 Investigators. Trastuzumab Deruxtecan in Previously Treated HER2-Positive Gastric Cancer. N Engl J Med. 2020 Jun 18;382(25):2419-2430. Epub 2020 May 29. link to original article contains dosing details in manuscript PubMed NCT03329690
Paclitaxel & Ramucirumab
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Awaiting publication (DESTINY-Gastric04) | 2021-ongoing | Phase 3 (C) | Trastuzumab deruxtecan | In progress |
Note: Dosing information is from CT.gov.
Targeted therapy
- Ramucirumab (Cyramza) 8 mg/kg IV once per day on days 1 & 15
Chemotherapy
- Paclitaxel (Taxol) 80 mg/m2 IV once per day on days 1, 8, 15
28-day cycles
References
- DESTINY-Gastric04: NCT04704934