Pertuzumab, trastuzumab, and chemotherapy in HER2-positive gastric/gastroesophageal junction cancer: end-of-study analysis of the JACOB phase III randomized clinical trial

Autor: Josep Tabernero, Paulo M. Hoff, Lin Shen, Atsushi Ohtsu, Manish A. Shah, Asna Siddiqui, Sarah Heeson, Astrid Kiermaier, Harrison Macharia, Eleonora Restuccia, Yoon-Koo Kang
Přispěvatelé: Institut Català de la Salut, [Tabernero J] Servei d’Oncologia Mèdica, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. UVic-UCC, IOB-Quirón, Barcelona, Spain. [Hoff PM] IDOR, Hospital Vila Nova Star, Rede D’Or-Sao Luiz, Sao Paulo, Brazil. [Shen L] Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Gastrointestinal Oncology, Peking University Cancer Hospital and Institute, Haidian District, Beijing, People’s Republic of China. [Ohtsu A] Exploratory Oncology Research & Clinical Trial Center, National Cancer Center Hospital, Kashiwa, Japan. [Shah MA] Meyer Cancer Center at Weill Cornell Medical College, New York, NY, USA. [Siddiqui A] Product Development Oncology, Roche Products Limited, Welwyn Garden City, UK, Vall d'Hebron Barcelona Hospital Campus
Rok vydání: 2022
Předmět:
Cancer Research
Oncology
Therapeutics::Therapeutics::Drug Therapy::Antineoplastic Protocols::Therapeutics::Drug Therapy::Antineoplastic Combined Chemotherapy Protocols [ANALYTICAL
DIAGNOSTIC AND THERAPEUTIC TECHNIQUES
AND EQUIPMENT]
terapéutica::terapéutica::farmacoterapia::protocolos antineoplásicos::terapéutica::farmacoterapia::protocolos de quimioterapia antineoplásica combinada [TÉCNICAS Y EQUIPOS ANALÍTICOS
DIAGNÓSTICOS Y TERAPÉUTICOS]
Gastroenterology
Medicaments antineoplàstics - Ús terapèutic
neoplasias::neoplasias por localización::neoplasias del sistema digestivo::neoplasias gastrointestinales::neoplasias del esófago [ENFERMEDADES]
Digestive System::Gastrointestinal Tract::Upper Gastrointestinal Tract::Esophagus::Esophagogastric Junction [ANATOMY]
sistema digestivo::tracto gastrointestinal::tracto gastrointestinal superior::esófago::unión esofagogástrica [ANATOMÍA]
General Medicine
Neoplasms::Neoplasms by Site::Digestive System Neoplasms::Gastrointestinal Neoplasms::Esophageal Neoplasms [DISEASES]
Quimioteràpia combinada
Esòfag - Càncer - Tractament
Zdroj: Scientia
ISSN: 1436-3305
1436-3291
0177-4786
DOI: 10.1007/s10120-022-01335-4
Popis: Background Dual-targeted anti-HER2 therapy significantly improves outcomes in HER2-positive breast cancer and could be beneficial in other HER2-positive cancers. JACOB’s end-of study analyses aimed to evaluate the long-term efficacy and safety of pertuzumab plus trastuzumab and chemotherapy for previously untreated HER2-positive metastatic gastric or gastroesophageal junction cancer. Methods Eligible patients were randomized 1:1 to pertuzumab/placebo plus trastuzumab and chemotherapy every 3 weeks. Primary endpoint: overall survival (OS). Secondary endpoints included progression-free survival (PFS), objective response rate (ORR), duration of response (DoR), and safety. Results The intention-to-treat population comprised 388 patients in the pertuzumab arm and 392 in the placebo arm. The safety population comprised 385 and 388 patients, respectively. Median follow-up was ≥ 44.4 months. Median OS was increased by 3.9 months (hazard ratio 0.85 [95% confidence intervals, 0.72–0.99]) and median PFS by 1.3 months (hazard ratio 0.73 [95% confidence intervals, 0.62–0.85]) in the pertuzumab vs. the placebo arm. ORR was numerically higher (57.0% vs. 48.6%) and median DoR 1.8 months longer with pertuzumab treatment. There was a trend for more favorable hazard ratios in certain subgroups related to HER2 amplification/overexpression. Safety was comparable between arms, except for serious and grade 3–5 adverse events, and any-grade diarrhea, which were more frequent with pertuzumab. Conclusions JACOB did not meet its primary endpoint. Nonetheless, the study continues to demonstrate some, albeit limited, evidence of treatment activity and an acceptable safety profile for pertuzumab plus trastuzumab and chemotherapy in previously untreated HER2-positive metastatic gastric or gastroesophageal junction cancer after long-term follow-up. Trial registration NCT01774786; https://clinicaltrials.gov/ct2/show/NCT01774786.
Databáze: OpenAIRE
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