Opdivo (Nivolumab) Plus Chemotherapy Demonstrates Significant Improvement in Overall and Progression-Free Survival as First-Line Treatment for Gastric and Esophageal Cancers

PRINCETON, N.J., Sept. 22, 2020 /PRNewswire/ -- Bristol-Myers Squibb (NYSE: BMY) today announced the primary results from the pivotal Phase 3 CheckMate -649 study. Opdivo (nivolumab) in combination with chemotherapy demonstrated statistically significant and clinically meaningful improvements in overall survival (OS) and progression-free survival (PFS) as a first-line treatment for patients with unresectable advanced or metastatic gastric cancer, gastroesophageal junction (GEJ) cancer, or esophageal adenocarcinoma, compared to chemotherapy alone. Opdivo is the first PD-1 inhibitor to demonstrate significant OS and PFS benefits when combined with chemotherapy versus chemotherapy alone in the treatment of gastric cancer, GEJ cancer, or esophageal adenocarcinoma. The study met both of its primary endpoints, with OS and PFS benefits observed in patients with PD-L1 positive expression, defined as a Combined Positive Score (CPS) ≥5. An OS benefit was also observed in the all-randomized population.

In patients with PD-L1–positive expression, defined as a Combined Positive Score (CPS) ≥5, the median OS in the Opdivo plus chemotherapy group was 14.4 months (95% CI: 13.1–16.2; hazard ratio [HR]: 0.71; 98.4% CI: 0.59–0.86; p<0.0001), compared with 11.1 months (95% CI: 10.0–12.1) in the chemotherapy-alone control group. The median PFS in the Opdivo plus chemotherapy group was 7.7 months (95% CI: 7.0–9.2; HR: 0.68; 98% CI: 0.56–0.81; p<0.0001), versus 6.0 months (95% CI: 5.6–6.9) in the chemotherapy-alone group. In this study, the safety profile of Opdivo in combination with chemotherapy was consistent with the known safety profiles of Opdivo and chemotherapy, and no new safety signals were observed.

Among studies investigating immune checkpoint inhibitor-based first-line therapy for gastric and esophageal cancers, CheckMate -649 is the largest randomized, global Phase III trial to date.

“Currently, chemotherapy is the first-line standard of care for patients with advanced or metastatic HER2-negative gastric or gastroesophageal junction cancer. Although chemotherapy is an important treatment option for these patients, those receiving chemotherapy alone as initial therapy typically achieve only limited survival benefits of less than one year,” said Dr. Markus Moehler, Professor of Clinical Gastrointestinal Oncology at the University Medical Center of Johannes Gutenberg University Mainz. “As no immunotherapy regimen has yet been approved for first-line treatment in this setting, there remains an urgent unmet need for innovative therapeutic options among patients with advanced or metastatic upper gastrointestinal cancers worldwide.”

The study results demonstrated that Opdivo in combination with chemotherapy also showed a statistically significant overall survival (OS) benefit in both patients with PD-L1 positivity and a Combined Positive Score (CPS) ≥1, as well as in the overall randomized population. In the overall randomized population, the median OS was 13.8 months (95% CI: 12.6–14.6) in the Opdivo plus chemotherapy group versus 11.6 months (95% CI: 10.9–12.5) in the chemotherapy-alone group (HR: 0.80; 99.3% CI: 0.68–0.94; p=0.0002). In patients with PD-L1 positivity and CPS ≥1, the median OS was 14.0 months (95% CI: 12.6–15.0) in the Opdivo plus chemotherapy group versus 11.3 months (95% CI: 10.6–12.3) in the chemotherapy-alone group (HR: 0.77; 99.3% CI: 0.64–0.92; p=0.0001).

“CheckMate -649 has recently become the first global study in over a decade to demonstrate a significant overall survival benefit surpassing chemotherapy as first-line treatment for HER2-negative gastric cancer, gastroesophageal junction cancer, or esophageal adenocarcinoma. Therefore, regardless of the specific tumor location, the regimen of Opdivo combined with chemotherapy is expected to become the new standard of care for first-line treatment in this patient population.” said Dr. Ian M. Waxman, Head of Gastrointestinal Oncology Research and Development at Bristol-Myers Squibb. “We will discuss the existing data from the CheckMate -649 study with health authorities worldwide, committed to bringing this important new treatment option to patients who truly need it.”

The incidence of treatment-related adverse events (TRAEs) of any grade and Grade 3–4 severity was slightly higher in the Opdivo plus chemotherapy group (22% for any grade; 17% for Grade 3–4) than in the chemotherapy-alone group (12% for any grade; 10% for Grade 3–4). In the Opdivo plus chemotherapy group, 36% and 17% of patients discontinued treatment due to TRAEs of any grade and Grade 3–4 severity, respectively, compared with 24% and 9% in the chemotherapy-alone group. Subgroup analyses showed that the incidence of TRAEs in the Opdivo plus chemotherapy group was generally consistent across all patient subgroups.

Responsible Editor: Liuli

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