2026-04-17T11:37:23Zhttps://recercat.cat/oai/request

oai:recercat.cat:11351/115422025-10-24T10:21:36Zcom_2072_378070com_2072_378040col_2072_378092

00925njm 22002777a 4500 dc Qiu, Miao-Zhen author Cruz-Correa, Marcia author OH, DO-YOUN author Arkenau, Hendrik-Tobias author Tabernero, Josep author Kato, Ken author 2024-06-03T12:09:28Z 2024-06-03T12:09:28Z 2024-05-28 Chemotherapy; Adenocarcinoma; Gastro-oesophageal junction Quimioterapia; Adenocarcinoma; Unión gastroesofágica Quimioteràpia; Adenocarcinoma; Unió gastroesofàgica Objective To evaluate the efficacy and safety of tislelizumab added to chemotherapy as first line (primary) treatment for advanced gastric or gastro-oesophageal junction adenocarcinoma compared with placebo plus chemotherapy. Design Randomised, double blind, placebo controlled, phase 3 study. Setting 146 medical centres across Asia, Europe, and North America, between 13 December 2018 and 28 February 2023. Participants 1657 patients aged ≥18 years with human epidermal growth factor receptor 2 negative locally advanced unresectable or metastatic gastric or gastro-oesophageal junction adenocarcinoma, regardless of programmed death-ligand 1 (PD-L1) expression status, who had not received systemic anticancer therapy for advanced disease. Interventions Patients were randomly (1:1) assigned to receive either tislelizumab 200 mg or placebo intravenously every three weeks in combination with chemotherapy (investigator’s choice of oxaliplatin and capecitabine, or cisplatin and 5-fluorouracil) and stratified by region, PD-L1 expression, presence or absence of peritoneal metastases, and investigator’s choice of chemotherapy. Treatment continued until disease progression or unacceptable toxicity. Main outcome measures The primary endpoint was overall survival, both in patients with a PD-L1 tumour area positivity (TAP) score of ≥5% and in all randomised patients. Safety was assessed in all those who received at least one dose of study treatment. Results Of 1657 patients screened between 13 December 2018 and 9 February 2021, 660 were ineligible due to not meeting the eligibility criteria, withdrawal of consent, adverse events, or other reasons. Overall, 997 were randomly assigned to receive tislelizumab plus chemotherapy (n=501) or placebo plus chemotherapy (n=496). Tislelizumab plus chemotherapy showed statistically significant improvements in overall survival versus placebo plus chemotherapy in patients with a PD-L1 TAP score of ≥5% (median 17.2 months v 12.6 months; hazard ratio 0.74 (95% confidence interval 0.59 to 0.94); P=0.006 (interim analysis)) and in all randomised patients (median 15.0 months v 12.9 months; hazard ratio 0.80 (0.70 to 0.92); P=0.001 (final analysis)). Grade 3 or worse treatment related adverse events were observed in 54% (268/498) of patients in the tislelizumab plus chemotherapy arm versus 50% (246/494) in the placebo plus chemotherapy arm. Conclusions Tislelizumab added to chemotherapy as primary treatment for advanced or metastatic gastric or gastro-oesophageal junction adenocarcinoma provided superior overall survival with a manageable safety profile versus placebo plus chemotherapy in patients with a PD-L1 TAP score of ≥5%, and in all randomised patients. Trial registration ClinicalTrials.gov NCT03777657 This study was funded by BeiGene. The funder had a role in study design, data collection, data analysis, data interpretation and writing of the clinical study report, and provided medical writing support. The clinical researchers were independent from the funder, and all authors had access to all relevant aggregated study data and provided final approval for the decision to submit the manuscript for publication. All authors take responsibility for the integrity of the data and the accuracy of the data analysis. http://hdl.handle.net/11351/11542 Quimioteràpia combinada Avaluació de resultats (Assistència sanitària) Adenocarcinoma - Tractament Estómac - Càncer - Tractament Esòfag - Càncer - Tractament ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT::Diagnosis::Prognosis::Treatment Outcome DISEASES::Neoplasms::Neoplasms by Histologic Type::Neoplasms, Glandular and Epithelial::Carcinoma::Adenocarcinoma Other subheadings::Other subheadings::Other subheadings::/drug therapy ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT::Therapeutics::Therapeutics::Drug Therapy::Antineoplastic Protocols::Therapeutics::Drug Therapy::Antineoplastic Combined Chemotherapy Protocols ANATOMY::Digestive System::Gastrointestinal Tract::Upper Gastrointestinal Tract::Esophagus::Esophagogastric Junction TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS::diagnóstico::pronóstico::resultado del tratamiento ENFERMEDADES::neoplasias::neoplasias por tipo histológico::neoplasias glandulares y epiteliales::carcinoma::adenocarcinoma Otros calificadores::Otros calificadores::Otros calificadores::/farmacoterapia TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS::terapéutica::terapéutica::farmacoterapia::protocolos antineoplásicos::terapéutica::farmacoterapia::protocolos de quimioterapia antineoplásica combinada ANATOMÍA::sistema digestivo::tracto gastrointestinal::tracto gastrointestinal superior::esófago::unión esofagogástrica Tislelizumab plus chemotherapy versus placebo plus chemotherapy as first line treatment for advanced gastric or gastro-oesophageal junction adenocarcinoma: RATIONALE-305 randomised, double blind, phase 3 trial