Phase 3, randomised trial of avelumab versus physician’s choice of chemotherapy as third-line treatment for patients with advanced gastric or gastro-oesophageal junction cancer: primary analysis of JAVELIN Gastric 300

Abstract

Background

There currently are no internationally recognised treatment guidelines for patients with advanced gastric cancer/gastro-oesophageal junction cancer (GC/GEJC) in whom two prior lines of therapy have failed. The randomised, phase 3 JAVELIN Gastric 300 trial compared avelumab vs physician's choice of chemotherapy as third-line therapy in patients with advanced GC/GEJC.

Patients and methods

Patients with unresectable, recurrent, locally advanced, or metastatic GC/GEJC were recruited at 147 sites globally. All patients were randomised to receive either avelumab 10 mg/kg by intravenous infusion every 2 weeks or physician's choice of chemotherapy (paclitaxel 80 mg/m² on days 1, 8, and 15 or irinotecan 150 mg/m² on days 1 and 15, each of a 4-week treatment cycle); patients ineligible for chemotherapy received best supportive care. The primary endpoint was overall survival (OS). Secondary endpoints included progression-free survival (PFS), objective response rate (ORR), and safety.

Results

A total of 371 patients were randomised. The trial did not meet its primary endpoint of improving OS (median, 4.6 vs 5.0 months; hazard ratio [HR] = 1.1 [95% CI 0.9–1.4]; P = 0.81) or the secondary endpoints of PFS (median, 1.4 vs 2.7 months; HR = 1.73 [95% CI 1.4–2.2]; P > 0.99) or ORR (2.2% vs 4.3%) in the avelumab vs chemotherapy arms, respectively. Treatment-related adverse events (TRAEs) of any grade occurred in 90 patients (48.9%) and 131 patients (74.0%) in the avelumab and chemotherapy arms, respectively. Grade ≥3 TRAEs occurred in 17 patients (9.2%) in the avelumab arm and in 56 patients (31.6%) in the chemotherapy arm.

Conclusions

Treatment of patients with GC/GEJC with single-agent avelumab in the third-line setting did not result in an improvement in OS or PFS compared to chemotherapy. Avelumab showed a more manageable safety profile than chemotherapy.

Trial registration

ClinicalTrials.gov: NCT02625623