| Abstrakt: |
Key Points: Question: Does adding sintilimab, an IgG4 monoclonal antibody that binds to programmed cell death 1 (PD-1), to first-line chemotherapy improve survival for patients with previously untreated advanced gastric and gastroesophageal junction adenocarcinoma, both overall and in the subset of patients with the PD ligand 1 (PD-L1) combined positive score (CPS) of 5 or more? Findings: In this randomized clinical trial of 650 patients, from 62 centers in China, with previously untreated advanced gastric or gastroesophageal junction adenocarcinoma, the combination of sintilimab with chemotherapy compared with placebo with chemotherapy significantly improved overall survival in all randomized patients (median, 15.2 vs 12.3 months) and in patients with a CPS of 5 or more (median, 18.4 vs 12.9 months). Meaning: Among patients with previously untreated advanced gastric or gastroesophageal junction adenocarcinoma, adding sintilimab to chemotherapy significantly improved overall survival, compared with placebo with chemotherapy, among all randomized patients and in patients with a CPS of 5 or more. Importance: Gastric and gastroesophageal junction cancers are diagnosed in more than 1 million people worldwide annually, and few effective treatments are available. Sintilimab, a recombinant human IgG4 monoclonal antibody that binds to programmed cell death 1 (PD-1), in combination with chemotherapy, has demonstrated promising efficacy. Objective: To compare overall survival of patients with unresectable locally advanced or metastatic gastric or gastroesophageal junction cancers who were treated with sintilimab with chemotherapy vs placebo with chemotherapy. Also compared were a subset of patients with a PD ligand 1 (PD-L1) combined positive score (CPS) of 5 or more (range, 1-100). Design, Setting, and Participants: Randomized, double-blind, placebo-controlled, phase 3 clinical trial conducted at 62 hospitals in China that enrolled 650 patients with unresectable locally advanced or metastatic gastric or gastroesophageal junction adenocarcinoma between January 3, 2019, and August 5, 2020. Final follow-up occurred on June 20, 2021. Interventions: Patients were randomized 1:1 to either sintilimab (n = 327) or placebo (n = 323) combined with capecitabine and oxaliplatin (the XELOX regimen) every 3 weeks for a maximum of 6 cycles. Maintenance therapy with sintilimab or placebo plus capecitabine continued for up to 2 years. Main Outcomes and Measures: The primary end point was overall survival time from randomization. Results: Of the 650 patients (mean age, 59 years; 483 [74.3%] men), 327 were randomized to sintilimab plus chemotherapy and 323 to placebo plus chemotherapy. Among the randomized patients, 397 (61.1%) had tumors with a PD-L1 CPS of 5 or more; 563 (86.6%) discontinued study treatment and 388 (59.7%) died; 1 patient (<0.1%) was lost to follow-up. Among all randomized patients, sintilimab improved overall survival compared with placebo (median, 15.2 vs 12.3 months; stratified hazard ratio [HR], 0.77 [95% CI, 0.63-0.94]; P =.009). Among patients with a CPS of 5 or more, sintilimab improved overall survival compared with placebo (median, 18.4 vs 12.9 months; HR, 0.66 [95% CI, 0.50-0.86]; P =.002). The most common grade 3 or higher treatment-related adverse events were decreased platelet count (sintilimab, 24.7% vs placebo, 21.3%), decreased neutrophil count (sintilimab, 20.1% vs placebo, 18.8%), and anemia (sintilimab, 12.5% vs placebo, 8.8%). Conclusions and Relevance: Among patients with unresectable locally advanced or metastatic gastric and gastroesophageal junction adenocarcinoma treated with first-line chemotherapy, sintilimab significantly improved overall survival for all patients and for patients with a CPS of 5 or more compared with placebo. Trial Registration: ClinicalTrials.gov Identifier: NCT03745170 This randomized clinical trial evaluates whether sintilimab plus chemotherapy vs placebo plus chemotherapy improved overall survival in patients in China with unresectable, locally advanced, recurrent, or metastatic gastric or gastroesophageal junction adenocarcinoma. [ABSTRACT FROM AUTHOR] |
