Since completion of the Trastuzumab for Gastric Cancer study, trastuzumab with doublet chemotherapy (a fluoropyrimidine and a platinum) has been the gold-standard first-line therapy for patients with locally advanced unresectable or metastatic human epidermal growth factor receptor 2-positive (HER2+) gastroesophageal adenocarcinoma (GEA). The safety and efficacy of 23 studies of first-line trastuzumab plus doublet chemotherapy, without checkpoint inhibitors (n = 19) or with checkpoint inhibitors (n = 4), conducted in patients with locally advanced unresectable or metastatic HER2+ GEA, including phase II/III, prospective, and retrospective observational studies, were summarized. In studies without checkpoint inhibitors, the median duration of trastuzumab treatment ranged from 19.5 to 39.0 weeks and from 15.3 to 30.0 weeks for chemotherapy. In studies with checkpoint inhibitors, the median duration of pembrolizumab/trastuzumab/chemotherapy was 30 weeks, and 18 weeks for chemotherapy. In studies without checkpoint inhibitors, treatment-emergent adverse events (TEAEs) of grade ≥3 ranged from 32% to 84%. Serious adverse events (SAEs) ranged from 15% to 39%. Adverse events resulting in discontinuation ranged from 0% to 30%. Treatment-related deaths occurred in 0%-9% of patients. In studies with checkpoint inhibitors, TEAEs of grade ≥3 were 57%. SAEs ranged from 31% to 38%. Adverse events resulting in discontinuation ranged from 5% to 24%. Treatment-related deaths occurred in 0%-3% of patients. In studies without checkpoint inhibitors, objective response rate (ORR) ranged from 39% to 82%, median progression-free survival (PFS) from 5.7 to 11.6 months, and median overall survival (OS) from 11.2 to 27.6 months. In studies with checkpoint inhibitors, ORR ranged from 39% to 86%, median PFS from 8.0 to 13.0 months, and median OS from 19.3 to 27.3 months. This review provides a historical benchmark on safety and efficacy of available first-line chemotherapy-based standard of care for patients with locally advanced unresectable or metastatic HER2+ GEA.
|Publication status||Published - 2022 Feb|
Bibliographical noteFunding Information:
Medical writing and/or editorial assistance was provided by Emily Cullinan, PhD, CMPP, and Francesca Balordi, PhD, of The Lockwood Group (Stamford, CT, USA), in accordance with Good Publication Practice (GPP3) guidelines, funded by MacroGenics, Inc .
Medical writing and/or editorial assistance was provided by Emily Cullinan, PhD, CMPP, and Francesca Balordi, PhD, of The Lockwood Group (Stamford, CT, USA), in accordance with Good Publication Practice (GPP3) guidelines, funded by MacroGenics, Inc. Funding for this review was provided by MacroGenics, Inc. DVTC reports personal fees from Archer, Astellas Pharma, Bristol-Myers Squibb, Daiichi Sankyo, Five Prime, Foundation Medicine, Guardant Health, Genentech/Roche, Gritstone Oncology, Lilly, Merck, Natera, Pieris Pharmaceuticals, QED Therapeutics, Seattle Genetics, Taiho Pharmaceutical, Tempus Labs, and Zymeworks; HCC has received consultation fees from Taiho Pharmaceutical, Celltrion, Merck Sharpe & Dohme, Eli Lilly, Bristol Myers Squibb, Merck-Serono, Gloria Pharmaceuticals, BeiGene, Amgen, and Zymeworks; grants to institution for clinical trial from Eli Lilly, GlaxoSmithKline, Merck Sharpe & Dohme, Merck-Serono, Bristol Myers Squibb/Ono Pharmaceutical, Taiho Pharmaceutical, Amgen, BeiGene, and Incyte; and honoraria from Merck-Serono and Eli Lilly; LS reports grants from Beijing Xiantong Biomedical Technology, Beihai Kangcheng (Beijing) Medical Technology, Boehringer Ingelheim, Jacobio Pharmaceuticals, Qilu Pharmaceutical, and Zaiding Pharmaceutical (Shanghai); and consulting fees from Harbour BioMed and Merck; MM reports grants and nonfinancial support from Arbeitsgemeinschaft Internistische Onkologie, German Ministry of Education and Research, the European Organisation for Research and Treatment of Cancer, and German Cancer Aid; personal fees from Amgen, Bristol-Myers Squibb, Falk Foundation, Lilly, MCI Group, Merck Serono, Merck Sharp & Dohme Corp. Pfizer and Roche; grants to the university from Amgen, Bristol-Myers Squibb, Merck Serono, Merck Sharp & Dohme Corp. and Pfizer; and nonfinancial support from Amgen and Bristol-Myers Squibb; HHY reports honoraria for advisory board and steering committee from MacroGenics, honoraria for advisory boards from Bristol-Myers Squibb and Zymeworks, and honoraria for steering committees from BeiGene and Merck; Y-KK reports consulting fees from ALX Oncology, Amgen, Astellas Pharma, Bristol-Myers Squibb, Daehwa Pharmaceutical, MacroGenics, Merck, Novartis, Ono Pharmaceutical, Surface Oncology, Taiho Pharmaceutical, and Zymeworks; MKR is a full-time employee of MacroGenics. Not applicable. Not applicable.
© 2021 The Authors
All Science Journal Classification (ASJC) codes
- Cancer Research