Gastric cancer, HER2-positive

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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.

12 regimens on this page
13 variants on this page


Guidelines

CAP/ASCP/ASCO

Metastatic or locally advanced disease, first-line

Capecitabine & Cisplatin (CX)

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 3 (C) 1. CF & Trastuzumab
2. 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 Years 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

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 3 (E-RT-esc) 1. CF
2. CX
Superior OS
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 OS
Median OS: 14.2 vs 17.5 mo
(HR 1.19, 95% CI 1.00-1.41)

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

CapeOx

CapeOx: Capecitabine and Oxaliplatin

Regimen

Study Years 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 Years of enrollment Evidence Comparator Comparative Efficacy
Janjigian et al. 2021 (KEYNOTE-811) 2018-2020 Phase 3 (E-RT-esc) 1. CapeOx & Trastuzumab
2. CF & Trastuzumab
Superior ORR1

1This is an interim secondary endpoint; primary endpoints are PFS and OS.

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 contains dosing details in manuscript PubMed NCT03615326

CapeOx & Trastuzumab

CapeOx & Trastuzumab: Capecitabine, Oxaliplatin, Trastuzumab

Regimen

Study Years of enrollment Evidence Comparator Comparative Efficacy
Janjigian et al. 2021 (KEYNOTE-811) 2018-2020 Phase 3 (C) 1. CapeOx, Pembrolizumab, Trastuzumab
2. 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 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

Cisplatin & Fluorouracil (CF)

CF: Cisplatin & Fluorouracil
FP: Fluorouracil & Platinol (Cisplatin)

Regimen

Study Years of enrollment Evidence Comparator Comparative Efficacy
Bang et al. 2010 (ToGA) 2005-2008 Phase 3 (C) 1. CF & Trastuzumab
2. 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 Years of enrollment Evidence Comparator Comparative Efficacy
Bang et al. 2010 (ToGA) 2005-2008 Phase 3 (E-esc) 1. CF
2. CX
Superior OS
Median OS: 13.8 vs 11.1 mo
(HR 0.74, 95% CI 0.60-0.91)

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. HERIZON-GEA-01: NCT05152147
  3. KEYNOTE-811: NCT03615326

Metastatic or locally advanced disease, subsequent lines of therapy

Docetaxel monotherapy

Regimen

Study Years of enrollment Evidence Comparator Comparative Efficacy
Thuss-Patience et al. 2017 (GATSBY) 2012-2013 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 Years 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:
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

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 Years 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 Years of enrollment Evidence Comparator Comparative Efficacy
Thuss-Patience et al. 2017 (GATSBY) 2012-2013 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

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 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 Years 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