Nivolumab with chemotherapy

In a randomized, open-label, international, phase III study (CheckMate-649 [NCT02872116]), patients with HER2-negative gastric or gastroesophageal junction adenocarcinomas were randomly assigned 1:1:1 to receive either nivolumab with chemotherapy (nivolumab 360 mg with CAPOX every 3 weeks or nivolumab 240 mg with leucovorin, 5-FU, and oxaliplatin [FOLFOX] every 2 weeks), chemotherapy alone (CAPOX every 3 weeks or FOLFOX every 2 weeks), or nivolumab 1 mg/kg and ipilimumab 3 mg/kg every 3 weeks × 4 (followed by maintenance nivolumab). The trial randomly assigned 1,581 patients (including 955 with PD-L1 CPS ≥5) to the chemotherapy-plus-nivolumab arm (n = 789; n = 473 with PD-L1 CPS ≥5) or the chemotherapy-alone arm (n = 792; n = 482 with PD-L1 CPS ≥5).[28]

In a randomized, open-label, international, phase III study (CheckMate-649 [NCT02872116]), patients with HER2-negative gastric or gastroesophageal junction adenocarcinomas were randomly assigned 1:1:1 to receive either nivolumab with chemotherapy (nivolumab 360 mg with CAPOX every 3 weeks or nivolumab 240 mg with leucovorin, 5-FU, and oxaliplatin [FOLFOX] every 2 weeks), chemotherapy alone (CAPOX every 3 weeks or FOLFOX every 2 weeks), or nivolumab 1 mg/kg and ipilimumab 3 mg/kg every 3 weeks × 4 (followed by maintenance nivolumab). The trial randomly assigned 1,581 patients (including 955 with PD-L1 CPS ≥5) to the chemotherapy-plus-nivolumab arm (n = 789; n = 473 with PD-L1 CPS ≥5) or the chemotherapy-alone arm (n = 792; n = 482 with PD-L1 CPS ≥5).[28]

For all patients (regardless of PD-L1 status), the median OS was 14.0 months (95% CI, 12.6–15.0) in the nivolumab-plus-chemotherapy arm compared with 11.3 months (95 % CI, 10.6–12.3) in the chemotherapy-alone arm (HR, 0.77; 99.3% CI, 0.64–0.92; P < .0001).

In a randomized, open-label, international, phase III study (CheckMate-649 [NCT02872116]), patients with HER2-negative gastric or gastroesophageal junction adenocarcinomas were randomly assigned 1:1:1 to receive either nivolumab with chemotherapy (nivolumab 360 mg with CAPOX every 3 weeks or nivolumab 240 mg with leucovorin, 5-FU, and oxaliplatin [FOLFOX] every 2 weeks), chemotherapy alone (CAPOX every 3 weeks or FOLFOX every 2 weeks), or nivolumab 1 mg/kg and ipilimumab 3 mg/kg every 3 weeks × 4 (followed by maintenance nivolumab). The trial randomly assigned 1,581 patients (including 955 with PD-L1 CPS ≥5) to the chemotherapy-plus-nivolumab arm (n = 789; n = 473 with PD-L1 CPS ≥5) or the chemotherapy-alone arm (n = 792; n = 482 with PD-L1 CPS ≥5).[28]

Patients with tumors with PD-L1 CPS greater than 5 had a median OS of 14.4 months (95% CI, 13.1–16.2) in the nivolumab-plus-chemotherapy arm compared with 11.1 months (95% CI, 10.0−12.1) in the chemotherapy-alone arm (HR, 0.71; 98.4% CI, 0.59–0.86; P = .0001).

In a randomized, open-label, international, phase III study (CheckMate-649 [NCT02872116]), patients with HER2-negative gastric or gastroesophageal junction adenocarcinomas were randomly assigned 1:1:1 to receive either nivolumab with chemotherapy (nivolumab 360 mg with CAPOX every 3 weeks or nivolumab 240 mg with leucovorin, 5-FU, and oxaliplatin [FOLFOX] every 2 weeks), chemotherapy alone (CAPOX every 3 weeks or FOLFOX every 2 weeks), or nivolumab 1 mg/kg and ipilimumab 3 mg/kg every 3 weeks × 4 (followed by maintenance nivolumab). The trial randomly assigned 1,581 patients (including 955 with PD-L1 CPS ≥5) to the chemotherapy-plus-nivolumab arm (n = 789; n = 473 with PD-L1 CPS ≥5) or the chemotherapy-alone arm (n = 792; n = 482 with PD-L1 CPS ≥5).[28]

Grades 3 and 4 adverse events occurred in 462 patients in the combination arm and in 341 patients in the chemotherapy-alone arm.[28][Level of evidence A1]