Chinese patients with advanced gastric cancer, gastroesophageal junction (GEJ) cancer, or esophageal adenocarcinoma demonstrated a clinically meaningful, long-term improvement in overall survival (OS) compared with chemotherapy alone after first-line treatment with Opdivo (nivolumab) plus chemotherapy during the phase 3 CheckMate 649 trial.
Updated data presented at the 2025 Gastrointestinal Cancers Symposium demonstrated that, at a minimum follow-up of 61.2 months for the Chinese population treated during the study, Opdivo plus chemotherapy (99 patients) generated a median OS of 14.3 months compared with 10.3 months for chemotherapy alone (109 patients) The 60-month OS rates were 20% and 7%, respectively.
Among patients with a PD-L1 combined positive score (CPS) of at least 5, those in the Opdivo group (75 patients) achieved a median OS of 15.5 months versus 9.6 months for patients in the chemotherapy group (81 patients). The respective 60-month OS rates were 24% and 8%.
Glossary:
Thrombocytopenia: low platelet count.
Neutropenia: low neutrophil count.
Overall survival (OS): how long patients live after diagnosis.
Progression-free survival (PFS): how long patients live without disease progression.
Objective response rate (ORR): percentage of patients showing tumor shrinkage.
Complete response (CR): tumor is completely gone.
Partial response (PR): tumor shrinks by at least 30%.
Stable disease (SD): tumor neither shrinks nor grows.
Progressive disease (PD): tumor grows.
Duration of response (DOR): how long a response lasts.
ECOG performance status: a measure of a patient's general health.
PD-L1 combined positive score (CPS): a measure of PD-L1 expression on tumor cells.
Immunologic etiology: immune system-related cause of disease.
The OS benefit with Opdivo plus chemotherapy was consistent across prespecified subgroups in the Chinese population.
In the overall population, the median progression-free survival (PFS) was 8.3 months for the Opdivo group versus 5.6 months for the chemotherapy alone group. In the population with a PD-L1 CPS of at least 5, the median PFS was 8.5 months and 4.3 months for Opdivo plus chemotherapy and chemotherapy alone, respectively.
“These extended follow-up results align with the overall CheckMate 649 trial population, reinforcing Opdivo plus chemotherapy as the standard first-line treatment for Chinese patients with advanced gastric cancer, GEJ cancer, [or] esophageal adenocarcinoma,” lead study author Dr. Lin Shen, and colleagues wrote in a poster presentation of the data.
Shen is vice president of Clinical Oncology at Beijing Cancer Hospital and Peking University, as well as deputy director at Beijing Institute for Cancer Research in China.
In April 2021, the FDA approved Opdivo combined with select types of chemotherapy for the frontline treatment of patients with advanced or metastatic gastric cancer, GEJ cancer, and esophageal adenocarcinoma, based on prior data from CheckMate 649.
Safety and Additional Efficacy Data for the Chinese Population
No new safety signals with Opdivo plus chemotherapy were reported with longer-term follow-up. Any-grade treatment-related side effects (TRAEs) occurred in 99% of patients in the Opdivo group versus 94% of patients in the control group. The rates of grade 3 (severe) or 4 (life-threatening) TRAEs were 66% and 50%, respectively. Serious any-grade TRAEs were reported in 26% of patients in the experimental group versus 13% of patients in the chemotherapy alone group. The respective rates of grade 3 or 4 serious TRAEs were 19% and 10%.
The most common grade 3 or 4 TRAEs reported in the Opdivo group included decreased neutrophil count (17%), decreased platelet count (7%), thrombocytopenia (7%), decreased white blood cell count (6%), anemia (6%) and neutropenia (6%).
In the chemotherapy alone group, the most frequent grade 3 or 4 TRAEs comprised decreased platelet count (11%), decreased neutrophil count (11%), neutropenia (8%) and vomiting (5%).
TRAEs led to treatment discontinuation in 51% of patients in the Opdivo group versus 26% of patients in the chemotherapy alone group. Four treatment-related deaths (4%) were reported in the experimental group versus 1 treatment-related death (1%) in the control group.
Notably, grade 3 or 4 TRAEs with potential immunologic etiology occurred in no more than 7% of Chinese patients in the Opdivo plus chemotherapy group across organ categories; no grade 5 (death) events occurred in either group.
In the overall population, the ORR was 66% in the Opdivo group versus 45% in the chemotherapy alone group. In the experimental group, the complete response (CR), partial response (PR), stable disease (SD) and progressive disease (PD) rates were 17%, 49%, 25% and 9%, respectively. These respective rates were 8%, 37%, 30% and 14% in the control group.
The median duration of response (DOR) in the overall population was 12.5 months for the Opdivo group versus 5.6 months for the chemotherapy alone group.
In the PD-L1 CPS of at least 5 population, the ORR was 68% in the Opdivo group versus 48% in the chemotherapy alone group. The respective CR, PR, SD and PD in the Opdivo group were 19%, 49%, 23% and 9%. These respective rates were 11%, 37%, 25% and 17% in the control group. The median DOR in this population was 12.5 months and 6.9 months for the experimental and control groups, respectively.
The OS, PFS and ORR benefits with the Opdivo regimen were consistent across different PD-L1 CPS subgroups.
Among all randomly assigned patients in the experimental group, patients who responded to Opdivo plus chemotherapy (49 patients) experienced a median OS of 21.5 months compared with nine months for those who had SD or PD (33 patients). In the chemotherapy group, responders (42 patients) achieved a median OS of 14.5 months versus 9.1 months for non-responders (34 patients).
In the population of patients with a PD-L1 CPS of at least 5, those who responded to Opdivo plus chemotherapy (40 patients) had a median OS of 23.3 months versus 11.5 months for those who did not respond to the experimental regimen (23 patients). In the chemotherapy group, the median OS was 13.1 months for responders (33 patients) versus 9.1 months for non-responders (22 patients).
CheckMate 649 Overview
The randomized, open-label, global phase 3 study enrolled patients with previously untreated, unresectable, advanced or metastatic gastric cancer, GEJ cancer and esophageal adenocarcinoma. Patients were not permitted to have HER2-positive disease, and an ECOG performance status of 0 to 1 was required.
Patients were randomly assigned in a 1:1:1 fashion. In the first experimental group, patients received Opdivo at 360 milligrams (mg) in combination with XELOX (oxaliplatin and capecitabine) once every three weeks; or Opdivo at 240 mg plus FOLFOX (oxaliplatin, leucovorin and fludarabine) once every two weeks. In the control group, patients received chemotherapy alone in the form of XELOX once every three weeks or FOLFOX once every two weeks. Treatment continued until disease progression, unacceptable toxicity, withdrawal of consent or end of study.
In the Opdivo group, 15% of patients received FOLFOX, and 85% were given XELOX. These rates were 13% and 87%, respectively, in the control group.
The study also included a second experimental group where patients received Opdivo at 1 mg per kilogram (mg/kg) plus Yervoy (ipilimumab) at 3 mg/kg once every three weeks for 4 cycles, followed by Opdivo alone at 240 mg once every two weeks.
Blinded independent central review–assessed PFS and OS in the population of patients with a PD-L1 CPS of at least 5 served as the trial’s dual primary end goal. Secondary end goals included OS and PFS in the overall population, the population of patients with a PD-L1 CPS of at least 1 and the population of patients with a PD-L1 CPS of at least 10; and overall response rate.
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Reference
“First-line (1L) nivolumab (NIVO) plus chemotherapy (chemo) versus chemo in patients (pts) with advanced gastric cancer, gastroesophageal junction cancer, and esophageal adenocarcinoma (GC/GEJC/EAC): 5-year (y) follow-up of Chinese pts from CheckMate 649.” By Dr. Shen L et al. J Clin Oncol. 2025; suppl.392
