Avelumab (anti-PD-L1) as first-line switch-maintenance or second-line therapy in patients with advanced gastric or gastroesophageal junction cancer: phase 1b results from the JAVELIN Solid Tumor trial

Abstract

BackgroundWe evaluated the antitumor activity and safety of avelumab, a human anti-PD-L1 IgG1 antibody, as first-line switch-maintenance (1L-mn) or second-line (2L) treatment in patients with advanced gastric/gastroesophageal cancer (GC/GEJC) previously treated with chemotherapy.MethodsIn a phase 1b expansion cohort, patients without (1L-mn) or with (2L) disease progression following first-line chemotherapy for advanced GC/GEJC received avelumab 10mg/kg intravenously every 2weeks. Endpoints included best overall response, progression-free survival (PFS), overall survival (OS), and safety.ResultsOverall, 150 patients were enrolled (1L-mn, n=90; 2L, n=60) and median follow-up in the 1L-mn and 2L subgroups was 36.0 and 33.7months, respectively. The confirmed objective response rate was 6.7% in both subgroups (95% CI, 2.5-13.9% and 1.8-16.2%, respectively), including complete responses in 2.2% of the 1L-mn subgroup (n=2). In the 1L-mn and 2L subgroups, median duration of response was 21.4months (95% CI, 4.0-not estimable) and 3.5months (95% CI, 2.8-8.3) and disease control rates were 56.7 and 28.3%, respectively. Median PFS in the 1L-mn and 2L subgroups was 2.8months (95% CI, 2.3-4.1) and 1.4months (95% CI, 1.3-1.5), with 6-month PFS rates of 23.0% (95% CI, 14.7-32.4%) and 7.9% (95% CI, 2.6-17.2%), and median OS was 11.1months (95% CI, 8.9-13.7) and 6.6months (95% CI, 5.4-9.4), respectively. In the 1L-mn subgroup, median OS measured from start of 1L chemotherapy was 18.7months (95% CI, 15.4-20.6). Across both subgroups, 20.7% had an infusion-related reaction of any grade. Other common treatment-related adverse events (TRAEs) of any grade included fatigue (10.0%) and nausea (6.7%). Treatment-related serious adverse events occurred in 4.0% of patients. Overall, 8.7% had a grade3 TRAE, including 1 treatment-related death.ConclusionAvelumab showed clinical activity and an acceptable safety profile in patients with GC/GEJC.Trial registrationClinicalTrials.govNCT01772004; registered 21 January 2013.