As reported in the Journal of Clinical Oncology by Markus Moehler, MD, and colleagues, the phase III JAVELIN Gastric 100 trial showed no improvement in overall survival with avelumab maintenance vs continued chemotherapy after first-line induction in HER2-negative, unresectable, locally advanced or metastatic gastric or gastroesophageal junction cancer.

Study Details

In the open-label trial, 805 patients from sites in 17 countries, enrolled between December 2015 and November 2017, received 12 weeks of induction therapy consisting of one of three oxaliplatin/fluoropyrimidine regimens. Of these, 499 patients with disease control at end of induction were randomly assigned to receive avelumab maintenance at 10 mg/kg every 2 weeks (n = 249) or continued chemotherapy (n = 250), including 54 (30 vs 24) patients with PD-L1–positive tumors (expression in ≥ 1% of tumor cells).

Markus Moehler, MD

The primary endpoint was overall survival after induction chemotherapy in all randomly assigned patients or in the PD-L1–positive population.

Overall Survival

Median follow-up for overall survival was 24 months in both groups (minimum = 18 months).

Median overall survival was 10.4 months (95% confidence interval [CI] = 9.1–12.0 months) in the avelumab group vs 10.9 months (95% CI = 9.6–12.4 months) in the continued chemotherapy group (hazard ratio [HR] = 0.91, 95% CI = 0.74–1.11, P = .1779), with 24-month rates of 22.1% vs 15.5%.

In the prespecified PD-L1–positive population (n = 54), median overall survival was 16.2 months (95% CI = 8.2 months–not reached) vs 17.7 months (95% CI = 9.6 months–not reached; HR = 1.13, 95% CI = 0.57–2.23, P = .6352). In an exploratory analysis among 137 patients with PD-L1 combined positive score (CPS) ≥ 1, median overall survival was 14.9 months (95% CI = 8.7–17.3 months) vs 11.6 months (95% CI = 8.4–12.6 months; unstratified HR = 0.72, 95% CI = 0.49–1.05).

Median progression-free survival was 3.2 months vs 4.4 months among all patients (HR = 1.04, 95% CI = 0.85–1.28), 4.1 months vs 9.7 months in the prespecified PD-L1–positive population, and 4.3 months vs 5.1 months in the PD-L1 CPS ≥ 1 population (unstratified HR = 0.87, 95% CI = 0.60–1.27).

Objective response—consisting of additional or deepening tumor responses in patients with partial response or stable disease with induction chemotherapy—was observed in 13.3% vs 14.4% of patients.

Adverse Events

In the maintenance phase, treatment-related grade ≥ 3 adverse events occurred in 12.8% of patients in the avelumab group vs 32.8% of the chemotherapy group. The most commonly reported events in the avelumab group were increased amylase, increased lipase, asthenia, colitis, decreased appetite, hypertension, and pneumonitis in two patients (0.8%) each. The most commonly reported events in the chemotherapy group were neutropenia (8.0%), decreased neutrophil count (4.2%), and peripheral sensory neuropathy (3.4%). Serious treatment-related adverse events occurred in 7.8% vs 9.7% of patients, and treatment-related adverse events led to permanent discontinuation of treatment in 10.3% vs 27.3% of patients. One patient in the chemotherapy group died from a treatment-related adverse event (cerebrovascular event). In the avelumab group, 13.2% of patients had immune-related adverse events, including grade ≥ 3 events in eight (3.3%).

The investigators concluded: “Gastric 100 did not demonstrate superior overall survival with avelumab maintenance vs continued chemotherapy in patients with advanced gastric cancer or gastroesophageal junction cancer overall or in a prespecified PD-L1–positive population.”

Dr. Moehler, of the Department of Internal Medicine, Johannes-Gutenberg University, Mainz, Germany, is the corresponding author for the Journal of Clinical Oncology article.

Disclosure: The study was supported by Merck KGaA as part of an alliance with Pfizer. For full disclosures of the study authors, visit ascopubs.org.