Nivolumab Plus Chemotherapy Demonstrates Sustained Survival Benefit in Advanced Gastroesophageal Cancers

Five-year follow-up data from the phase 3 CheckMate 649 trial demonstrates that first-line nivolumab查看药品详情 (Opdivo查看药品详情) in combination with chemotherapy continues to provide a significant overall survival (OS) benefit compared to chemotherapy alone in patients with advanced gastric cancer (搜索)搜索该疾病, gastroesophageal junction (GEJ) cancer, and esophageal adenocarcinoma (搜索)搜索该疾病 (EAC). The study's extended follow-up reinforces nivolumab plus chemotherapy as a standard first-line treatment option for these cancers.

The updated results, presented at the 2025 ASCO Gastrointestinal Cancers Symposium, showed that in the subgroup of patients with a PD-L1 (搜索)搜索该靶点 combined positive score (CPS) of 5 or higher, the median OS was 14.4 months (95% CI, 13.1-16.2) with nivolumab查看药品详情 plus chemotherapy compared to 11.1 months (95% CI, 10.1-12.1) with chemotherapy alone (HR, 0.71; 95% CI, 0.61-0.81). The 5-year OS rates were 16% and 6%, respectively. These results highlight the lasting impact of the nivolumab combination in this patient population.

Sustained Progression-Free Survival

The progression-free survival (PFS) benefit initially reported with the addition of nivolumab查看药品详情 to chemotherapy was also sustained with longer follow-up. In patients with a PD-L1 (搜索)搜索该靶点 CPS of ≥5, the median PFS at 5 years was 8.3 months (95% CI, 7.0-9.4) in the nivolumab/chemotherapy arm versus 6.1 months (95% CI, 5.6-6.9) in the chemotherapy-alone arm (HR, 0.71; 95% CI, 0.61-0.82). Across all randomized patients, the 5-year median PFS was 7.8 months (95% CI, 7.1-8.6) versus 6.9 months (95% CI, 6.7-7.2), respectively (HR, 0.79; 95% CI, 0.71-0.89).

Durable Responses Observed

Five-year response data underscored the durability of the clinically meaningful activity of the nivolumab查看药品详情 combination in the frontline setting. The objective response rate (ORR) in the CPS ≥5 subgroup was 60% in the nivolumab/chemo arm compared with 45% in the control arm. The median duration of response (mDOR) was 9.6 months versus 7.0 months, respectively. Among all patients, the ORR was 58% versus 46% and the mDOR was 8.5 versus 6.9 months, respectively.

Outcomes in Chinese Patients

Analysis of Chinese patients enrolled in the CheckMate 649 trial revealed consistent benefits with the nivolumab查看药品详情 combination. At a minimum follow-up of 61.2 months, nivolumab plus chemotherapy (n = 99) yielded a median OS of 14.3 months (95% CI, 11.5-16.5) compared with 10.3 months (95% CI, 8.1-12.1) for chemotherapy alone (n = 109; HR, 0.63; 95% CI, 0.46-0.85). The 60-month OS rates were 20% and 7%, respectively. In patients with a PD-L1 (搜索)搜索该靶点 CPS of at least 5, the nivolumab arm (n = 75) achieved a median OS of 15.5 months (95% CI, 11.9-21.1) vs 9.6 months (95% CI, 8.09-12.1) for the chemotherapy arm (n = 81; HR, 0.57; 95% CI, 0.40-0.82), with 60-month OS rates of 24% and 8%, respectively.

Safety Profile

No new safety signals were observed with the extended follow-up. The most common grade 3/4 treatment-related adverse events (TRAEs) in the nivolumab查看药品详情 plus chemotherapy arm were neutropenia (16%), decreased neutrophil count (11%), anemia (6%), and increased lipase (6%). In the chemotherapy-alone arm, the most common grade 3/4 TRAEs were neutropenia (13%), decreased neutrophil count (9%), diarrhea (3%), peripheral neuropathy (3%), anemia (3%), and vomiting (3%).

Study Design

The CheckMate 649 trial was an open-label, randomized, global phase 3 study that enrolled patients with previously untreated, unresectable, advanced or metastatic gastric cancer (搜索)搜索该疾病, GEJ cancer, and EAC. Patients had no known HER2 positivity and an ECOG performance status of 0 or 1. Patients were randomized to nivolumab查看药品详情 plus chemotherapy (XELOX or FOLFOX), chemotherapy alone (XELOX or FOLFOX), or nivolumab plus ipilimumab查看药品详情. The primary endpoints were OS and PFS in patients with a PD-L1 (搜索)搜索该靶点 CPS of 5 or higher.