The addition of nivolumab to first-line chemotherapy resulted in superior progression-free survival (PFS) and overall survival (OS) in patients with advanced gastric cancers when compared with chemotherapy alone, according to study results presented at the ESMO Virtual Congress 2020.

Standard first-line chemotherapy is associated with poor outcomes in patients with advanced or metastatic HER-2–negative gastric cancer and gastroesophageal junction cancer, with a median OS of less than 1 year.

Markus Moehler, Johannes-Gutenberg University Clinic (Mainz, Germany), and colleagues conducted the CheckMate 649 phase 3 clinical trial to determine whether the addition of nivolumab, a PD-1 immune checkpoint inhibitor, to standard first-line chemotherapy would improve outcomes over chemotherapy alone.

The researchers randomly assigned 1,581 patients with previously untreated, unresectable gastric cancer, gastroesophageal junction cancer or esophageal adenocarcinoma, regardless of PD-L1 expression, to chemotherapy (XELOX every 3 weeks or FOLFOX) alone or with nivolumab (360 mg every 3 weeks or 240 mg every 2 weeks).

OS and PFS by blinded independent central review in a cohort of patients with a PD-L1 Combined Performance Score (CPS) ≥5 served as the study’s dual primary endpoints. The researchers also reported OS outcomes for the entire cohort, as well as patients with a PD-L1 CPS ≥1.

A total of 955 patients had a PD-L1 CPS ≥5 (nivolumab plus chemotherapy, n = 473; chemotherapy alone, n = 482). With a median follow-up of 12 months, the researchers observed a statistically significant improvement in OS (median, 14.4 months vs. 11.1 months; hazard ratio [HR], 0.71; 95% CI, 0.59-0.86; P < .0001) and PFS (median, 7.7 months vs. 6.1 months; HR, 0.68; 95% CI, 0.56-0.81; P < .0001) among patients assigned nivolumab.

The benefit of nivolumab extended to all other subgroups. Among patients with a PD-L1 CPS ≥1 (nivolumab plus chemotherapy, n = 641; chemotherapy alone, n = 655), those assigned the investigational combination achieved a median OS of 14 months, compared with 11.3 months in the chemotherapy arm (HR, 0.77; 95% CI, 0.64-0.92; P = .0001).

In all randomized patients (nivolumab plus chemotherapy, n = 789; chemotherapy alone, n = 792), the combination resulted in a median OS of 13.8 months, compared with 11.6 months in the chemotherapy arm (HR, 0.8; 95% CI, 0.68-0.94; P = .0002).

 “The results are clinically very relevant,” Salah-Eddin Al-Batran, director of the Institute of Clinical Cancer Research and Director of GI Oncology, at Krankenhaus Nordwest-University Cancer Centre in Germany, said in a press release. “Based on this trial, for patients with HER2-negative gastric adenocarcinoma, oesophageal adenocarcinoma, or gastro-oesophageal junctional adenocarcinoma with PD-L1 CPS >5 tumours, the addition of nivolumab to chemotherapy will become the standard of care for first-line treatment. The open question is the effect in patients who have a PD-L1 CPS <5.”

The researchers observed no new safety signals with nivolumab. In the population of patients with a PD-L1 CPS ≥5, 95% of patients assigned nivolumab and 88% of patients assigned chemotherapy alone had a treatment-related adverse event of any grade. Grade 3-4 treatment-related adverse events occurred in 59% of the combination arm and 44% of the chemotherapy arm.

The rates of treatment-related adverse events leading to continuation were 38% and 25%, respectively. Eight patients assigned nivolumab plus chemotherapy and four patients assigned chemotherapy alone died during treatment due to a treatment-related adverse event.

“Nivolumab plus chemotherapy represents a potential new standard first-line treatment option for these patients,” the researchers concluded.