Difference between revisions of "Gastric cancer, HER2-positive"

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[[#top|Back to Top]]
 
[[#top|Back to Top]]
 
</div>
 
</div>
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{{#lst:Section editor transclusions|gi}}
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{{#lst:Editorial board transclusions|gi}}
 
<big>'''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.'''</big>
 
<big>'''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.'''</big>
 
{| 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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</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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<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 2 onwards: 6 mg/kg IV once on day 1
+
**Cycles 2 to 6: 6 mg/kg IV once on day 1
−
'''21-day cycle for up to 6 cycles'''
+
**Cycle 7 onwards: 10 mg/kg IV once on day 1
−
</div>
+
'''21-day cycles'''
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
====Subsequent treatment====
 
−
*Trastuzumab maintenance
 
 
</div></div><br>
 
</div></div><br>
 
<div class="toccolours" style="background-color:#eeeeee">
 
<div class="toccolours" style="background-color:#eeeeee">
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|-
 
|-
 
|[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"
+
<!-- {| 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>]'''
 
|'''[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)
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|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.2C_Trastuzumab_88|CX, Pertuzumab, Trastuzumab]]
+
|[[#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] [http://www.ncbi.nlm.nih.gov/pmc/articles/pmc9813086/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/36066725/ PubMed]
+
##'''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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|2008-2012
 
|2008-2012
 
| style="background-color:#1a9851" |Phase 3 (C)
 
| style="background-color:#1a9851" |Phase 3 (C)
−
|[[#CapeOx_.26_Lapatinib_99|CapeOx & Lapatinib]]
+
|[[#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)
 
|-
 
|-
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</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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|-
 
|-
 
|[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"
+
<!-- {| 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>]'''
 
|'''[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_.2C_Fluorouracil_.28CF.29_.26_Trastuzumab|CF & Trastuzumab]]
+
|1a. [[#CapeOx_.26_Trastuzumab|CapeOx & Trastuzumab]]<br>1b. [[#Cisplatin_.26_Fluorouracil_.28CF.29_.26_Trastuzumab|CF & Trastuzumab]]
−
| style="background-color:#1a9850" |Superior ORR<sup>1</sup>
+
| 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>This is an interim secondary endpoint; primary endpoints are PFS and OS.''
+
''<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====
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**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 219: 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_.2C_Fluorouracil_.28CF.29.2C_Pembrolizumab.2C_Trastuzumab_88|CF, Pembrolizumab, Trastuzumab]]
+
|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 ORR<sup>1</sup>
+
| style="background-color:#d73027" |Inferior PFS<sup>1</sup><br><br>Might have inferior OS<sup>1</sup>
 
|-
 
|-
 
|}
 
|}
−
''<sup>1</sup>This is an interim secondary endpoint; primary endpoints are PFS and OS.''<br>
+
''<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 240: 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 272: 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 285: 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"
+
<!-- {| 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>]'''
 
|'''[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]]
 
|1a. [[#Cisplatin_.26_Fluorouracil_.28CF.29_4|CF]]<br>1b. [[#Capecitabine_.26_Cisplatin_.28CX.29|CX]]
 
| 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)
 
| 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 311: 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 326: 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_99|T-DM1]]
+
|[[#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 344: 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">
Line 356: Line 445:
 
|-
 
|-
 
|[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. [[#Irinotecan_monotherapy_2|Irinotecan]]<br>1b. [[#Paclitaxel_monotherapy|Paclitaxel]]
+
|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====
Line 378: Line 467:
 
'''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}}==
Line 408: 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">
Line 420: 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_99|T-DM1]]
+
|[[#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 433: 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 per day on days 1, 8, 15
+
*[[Paclitaxel (Taxol)]] 80 mg/m<sup>2</sup> IV once on day 1
−
'''21-day cycles'''
+
'''7-day cycles'''
 
</div></div><br>
 
</div></div><br>
 
<div class="toccolours" style="background-color:#eeeeee">
 
<div class="toccolours" style="background-color:#eeeeee">
Line 448: Line 538:
 
|2007-2009
 
|2007-2009
 
| style="background-color:#1a9851" |Phase 3 (C)
 
| style="background-color:#1a9851" |Phase 3 (C)
−
|[[#Lapatinib_.26_Paclitaxel_99|Lapatinib & Paclitaxel]]
+
|[[#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 468: 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 481: Line 571:
 
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
|-
 
|-
−
|[https://www.clinicaltrials.gov/ct2/show/NCT04704934 Awaiting publication (DESTINY-Gastric04)]
+
|[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)
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</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 12:16, 23 June 2024

Back to Top

Section editor
Traviszack.jpeg
 Travis Zack, MD, PhD
University of California San Francisco
San Francisco, CA, USA
LinkedIn

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

NCCN

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

21-day cycles

References

  1. 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

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

Targeted therapy

21-day cycles

References

  1. 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
  2. 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
  3. 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
    1. 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

Targeted therapy

21-day cycles

References

  1. 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
    1. 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

21-day cycle for up to 8 cycles

References

  1. 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
  2. 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

Immunotherapy

Targeted therapy

21-day cycle for up to 35 cycles (2 years)

References

  1. 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
    1. 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

Targeted therapy

21-day cycles

References

  1. 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
    1. 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

  1. 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

Targeted therapy

21-day cycles

References

  1. 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
  2. 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
    1. 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
  3. 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

Immunotherapy

Targeted therapy

21-day cycles

References

  1. 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
    1. 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

Chemotherapy

21-day cycles

References

  1. 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

21-day cycles

References

  1. 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

Chemotherapy

14-day cycles

References

  1. 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

Chemotherapy

7-day cycles


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

28-day cycles

References

  1. 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
  2. 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
  3. 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

Chemotherapy

28-day cycles

References

  1. DESTINY-Gastric04: NCT04704934
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