Difference between revisions of "Gastric cancer, HER2-positive"
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| style="background-color:#1a9851" |Randomized Phase II (E-RT-switch-ooc) | | style="background-color:#1a9851" |Randomized Phase II (E-RT-switch-ooc) | ||
|Investigator's choice of:<br> 1. [[#Irinotecan_monotherapy_2|Irinotecan]]<br> 2. [[#Paclitaxel_monotherapy|Paclitaxel]] | |Investigator's choice of:<br> 1. [[#Irinotecan_monotherapy_2|Irinotecan]]<br> 2. [[#Paclitaxel_monotherapy|Paclitaxel]] | ||
− | | style="background-color:#1a9850" |Superior OS | + | | style="background-color:#1a9850" |Superior OS<br>Median OS: 12.5 vs 8.4 mo<br>(HR 0.59, 95% CI 0.39-0.88) |
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Revision as of 02:00, 3 November 2021
Page editor | Section editor | ||
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Ivy Abraham, MD University of Illinois at Chicago Chicago, IL |
Neeta K. Venepalli, MD, MBA University of Illinois at Chicago Chicago, IL |
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.
15 regimens on this page
16 variants on this page
|
Guidelines
CAP/ASCP/ASCO
- 2017: Bartley et al. HER2 testing and clinical decision making in gastroesophageal adenocarcinoma PubMed
Metastatic or locally advanced disease, first-line
Capecitabine & Cisplatin (CX)
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CX: Cisplatin & Xeloda (Capecitabine)
XP: Xeloda (Capecitabine) & Platinol (Cisplatin)
Regimen
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Bang et al. 2010 (ToGA) | 2005-2008 | Phase III (C) | 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 verified protocol PubMed
Capecitabine & Cisplatin (CX) & Trastuzumab
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CX & Trastuzumab: Cisplatin, Xeloda (Capecitabine), Trastuzumab
Regimen variant #1, 80/1600
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Shah et al. 2017 (HELOISE) | 2011-2015 | Phase IIIb (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) 80 mg/m2 IV once on day 1
- Capecitabine (Xeloda) 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 (compared to HD-Trastuzumab at 10 mg/kg IV)
- Subsequent cycles: 6 mg/kg IV once on day 1
21-day cycle for up to 6 cycles
Subsequent treatment
- Trastuzumab maintenance
Regimen variant #2, 80/2000
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Bang et al. 2010 (ToGA) | 2005-2008 | Phase III (E-RT-esc) | CX | Superior OS |
Tabernero et al. 2018 (JACOB) | 2013-2016 | Phase III (C) | CX, Pertuzumab, Trastuzumab | Might have inferior OS |
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
- Subsequent cycles: 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 verified protocol 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 verified protocol 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 protocol PubMed NCT01774786
CapeOx
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CapeOx: Capecitabine and Oxaliplatin
Regimen
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Hecht et al. 2015 (LOGiC) | 2008-2012 | Phase III (C) | CapeOx & Lapatinib | Did not meet primary endpoint of OS |
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
CapeOx & Trastuzumab
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CapeOx & Trastuzumab: Capecitabine, Oxaliplatin, Trastuzumab
Regimen
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Awaiting publication (KEYNOTE-811) | 2018-ongoing | Phase III (C) | 1. CapeOx, Pembrolizumab, Trastuzumab 2. Cisplatin & Fluorouracil (CF), Pembrolizumab, Trastuzumab |
Inferior ORR1 |
1This is an interim secondary endpoint; primary endpoints are PFS and OS.
Note: to our knowledge, this regimen was not tested as an experimental arm in an RCT prior to becoming a standard comparator arm. Treatment details are from ClinicalTrials.gov.
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: NCT03615326
Cisplatin & Fluorouracil (CF)
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CF: Cisplatin & Fluorouracil
FP: Fluorouracil & Platinol (Cisplatin)
Regimen
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Bang et al. 2010 (ToGA) | 2005-2008 | Phase III (C) | CF & 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 verified protocol PubMed NCT01041404
Cisplatin & Fluorouracil (CF) & Trastuzumab
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CF & Trastuzumab: Cisplatin, Fluorouracil, Trastuzumab
Regimen
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Bang et al. 2010 (ToGA) | 2005-2008 | Phase III (E-esc) | CF | Superior OS |
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
- Subsequent cycles: 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 verified protocol PubMed NCT01041404
- KEYNOTE-811: NCT03615326
Metastatic or locally advanced disease, subsequent lines of therapy
Docetaxel monotherapy
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Regimen
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Thuss-Patience et al. 2017 (GATSBY) | 2012-2013 | Phase II/III (C) | T-DM1 | Did not meet primary endpoint of OS |
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
- Docetaxel (Taxotere) 75 mg/m2 IV once on day 1
21-day cycles
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 protocol PubMed NCT01641939
Fam-trastuzumab deruxtecan monotherapy
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Regimen
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Shitara et al. 2020 (DESTINY-Gastric01) | 2017-2019 | Randomized Phase II (E-RT-switch-ooc) | Investigator's choice of: 1. Irinotecan 2. Paclitaxel |
Superior OS Median OS: 12.5 vs 8.4 mo (HR 0.59, 95% CI 0.39-0.88) |
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
- Fam-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 verified protocol PubMed NCT03329690
Irinotecan monotherapy
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Regimen
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Shitara et al. 2020 (DESTINY-Gastric01) | 2017-2019 | Randomized Phase II (C) | Trastuzumab deruxtecan | Inferior OS |
=Biomarker eligibility criteria
- DESTINY-Gastric01: HER2 over-expression
Chemotherapy
- Irinotecan (Camptosar) 150 mg/m2 IV once on day 1
14-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 verified protocol PubMed NCT03329690
Paclitaxel monotherapy
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Regimen variant #1, 80 mg/m2 weekly
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Thuss-Patience et al. 2017 (GATSBY) | 2012-2013 | Phase II/III (C) | T-DM1 | Did not meet primary endpoint of OS |
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
- Paclitaxel (Taxol) 80 mg/m2 IV once per day on days 1, 8, 15
21-day cycles
Regimen variant #2, 80 mg/m2, 3 out of 4 weeks
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Satoh et al. 2014 (TyTAN) | 2007-2009 | Phase III (C) | Lapatinib & Paclitaxel | Did not meet primary endpoint of OS |
Shitara et al. 2020 (DESTINY-Gastric01) | 2017-2019 | Randomized Phase II (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 verified protocol 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 protocol 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 verified protocol PubMed NCT03329690
Paclitaxel & Ramucirumab
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Regimen
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
(DESTINY-Gastric04) | 2021-ongoing | Phase III (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