Bristol Myers Squibb announced that the European Commission (EC) has approved nivolumab in combination with fluoropyrimidine- and platinum-based combination chemotherapy for the first-line treatment of adult patients with HER2-negative advanced or metastatic gastric, gastroesophageal junction (GEJ), or oesophagal adenocarcinoma (EAC) whose tumours express PD-L1 with a combined positive score (CPS) ≥ 5.

The EC’s decision is based on results from the Phase 3 CheckMate -649 trial, in which first-line treatment with nivolumab plus leucovorin, 5-fluorouracil and oxaliplatin (FOLFOX) or capecitabine and oxaliplatin was compared with chemotherapy alone.

Results from the trial showed a statistically significant and clinically meaningful improvement in overall survival (OS) and progression-free survival (PFS) in patients with unresectable advanced or metastatic gastric cancer (GC), GEJ cancer (GEJC) or EAC whose tumours express PD-L1 with a CPS ≥ 5 (the primary endpoints of the study).

The statistically significant OS benefit shown with nivolumab plus chemotherapy was also observed in PD-L1 positive patients with CPS ≥ 1 and in the all-randomized population.

The safety profile observed for nivolumab plus chemotherapy in the CheckMate -649 trial was consistent with the known safety profiles of the individual treatments.

“This approval marks a great achievement for many patients with gastric, gastroesophageal junction and oesophagal adenocarcinomas, who now have a new treatment option that has demonstrated superior overall survival compared to the long-standing standard of care,” said Ian M. Waxman, M.D., development lead, gastrointestinal cancers, Bristol Myers Squibb.

“With limited advances for HER2-negative gastric cancers made in the past ten years, we are especially pleased to move the field forward and introduce this Opdivo-based combination for patients in the European Union.”

The EC approval allows for the use of nivolumab in combination with fluoropyrimidine and platinum-based combination chemotherapy for the first-line treatment of adult patients with HER2-negative advanced or metastatic gastric cancer, gastroesophageal junction (GEJ), or oesophagal adenocarcinoma (EAC), whose tumours express PD-L1 with a combined positive score (CPS) ≥ 5 in the 27 member states of the European Union, as well as Iceland, Liechtenstein, and Norway.

CheckMate -649 Efficacy and Safety Results in Patients with PD-L1 CPS ≥ 5

Results from CheckMate -649 include:

OS (minimum follow‑up of 19.4 months): Median OS was 14.4 months in patients receiving nivolumab chemotherapy (95% Confidence Interval [CI]: 13.1 to 16.3) compared to 11.1 months (95% CI: 10.0 to 12.1) in patients receiving chemotherapy alone (Hazard Ratio [HR] 0.69; 95% CI: 0.60 to 0.81).

PFS (minimum follow‑up of 19.4 months): Median PFS was 8.31 months in patients receiving nivolumab chemotherapy (95% CI: 7.03 to 9.26) vs. 6.05 months (95% CI: 5.55 to 6.90) in patients receiving chemotherapy alone (HR = 0.68; 95% CI: 0.59 to 0.79).

Safety: The most frequent adverse reactions were peripheral neuropathy (53%), nausea (48%), fatigue (44%), diarrhoea (39%), vomiting (31%), decreased appetite (29%), abdominal pain (27%), constipation (25%), musculoskeletal pain (20%), pyrexia (19%), rash (18%), stomatitis (17%), palmar-plantar erythrodysaesthesia syndrome (13%), cough (13%), oedema (including peripheral oedema) (12%), headache (11%), and upper respiratory tract infection (10%).

Source: Bristol Myers Squibb