FDA Approval Insights: Nivolumab Plus Chemo for Frontline Gastric Cancer

Welcome to OncLive On Air^®! I’m your host today, Jessica Hergert.

OncLive On Air^® is a podcast from OncLive^®, which provides oncology professionals with the resources and information they need to provide the best patient care. In both digital and print formats, OncLive^® covers every angle of oncology practice, from new technology to treatment advances to important regulatory decisions.

In today’s episode, we had the pleasure of speaking with Yelena Y. Janjigian, MD, a medical oncologist at Memorial Sloan Kettering Cancer Center, to discuss the FDA approval of nivolumab (Opdivo) plus chemotherapy for the frontline treatment of patients with advanced or metastatic gastric cancer, gastroesophageal junction (GEJ) cancer, and esophageal adenocarcinoma.

On April 16, 2021, the FDA approved nivolumab to be combined with select types of chemotherapy for the frontline treatment of patients with advanced or metastatic gastric cancer, GEJ cancer, and esophageal adenocarcinoma.

Data from the phase 3 CheckMate-649 trial (NCT02872116), which served as the basis for the approval, showed that nivolumab plus leucovorin, 5-fluorouracil, and oxaliplatin (FOLFOX) or capecitabine and oxaliplatin (CapeOX) resulted in a significant improvement in survival in treatment-naïve patients with PD-L1–positive advanced gastric cancer, GEJ cancer, and esophageal adenocarcinoma vs chemotherapy alone.

At a minimum follow-up of 12 months, the median overall survival (OS) with nivolumab/chemotherapy was 14.4 months (95% CI, 13.1-16.2) vs 11.1 months with chemotherapy alone (95% CI, 10-12.1) in patients with a PD-L1 combined positive score (CPS) of 5 or greater (HR, 0.71; 98.4% CI, 0.59-0.86; P <.0001); this translated to a 29% reduction in the risk of death with the nivolumab combination. Moreover, nivolumab plus chemotherapy resulted in a 32% reduction in the risk of disease progression or death vs chemotherapy alone (HR, 0.68; 95% CI, 0.56-0.81; P <.0001). The CheckMate-649 trial enrolled 1581 patients who were randomized 1:1 to receive nivolumab at a dose of 360 mg in combination with CapeOX given every 3 weeks or nivolumab at a dose of 240 mg with FOLFOX given every 2 weeks (n = 789) vs CapeOX or FOLFOX alone (n = 792). Sixty percent of patients had a PD-L1 CPS of 5 or greater.

The median OS in the combination arm was 14 months in patients with a PD-L1 CPS of 1 or greater vs 11.3 months in the chemotherapy-alone arm (HR, 0.77; 99.3% CI, 0.64-0.92; P = .0001). Additionally, the median OS with the combination vs chemotherapy alone was 13.8 months vs 11.6 months, respectively, among all patients who underwent randomization (HR, 0.80; 99.3% CI, 0.68-0.94; P = .0002).

The most common adverse effects with nivolumab plus chemotherapy include peripheral neuropathy, nausea, fatigue, diarrhea, vomiting, decreased appetite, abdominal pain,

constipation and musculoskeletal pain. The immunotherapy agent can also cause immune-mediated effects like pneumonitis, colitis, and hepatitis, as well as endocrinopathies and nephritis.

In our exclusive interview, Janjigian discussed the FDA approval of nivolumab plus chemotherapy in advanced or metastatic gastric cancer, gastroesophageal junction cancer, and esophageal adenocarcinoma, key findings from the pivotal CheckMate-649 trial, and future directions with immunotherapy in the field.