Abstract

BackgroundWe evaluated the antitumor activity and safety of avelumab, a human anti–PD-L1 IgG1 antibody, as first-line switch-maintenance (1 L-mn) or second-line (2 L) treatment in patients with advanced gastric/gastroesophageal cancer (GC/GEJC) previously treated with chemotherapy.MethodsIn a phase 1b expansion cohort, patients without (1 L-mn) or with (2 L) disease progression following first-line chemotherapy for advanced GC/GEJC received avelumab 10 mg/kg intravenously every 2 weeks. Endpoints included best overall response, progression-free survival (PFS), overall survival (OS), and safety.ResultsOverall, 150 patients were enrolled (1 L-mn, n = 90; 2 L, n = 60) and median follow-up in the 1 L-mn and 2 L subgroups was 36.0 and 33.7 months, 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 1 L-mn subgroup (n = 2). In the 1 L-mn and 2 L subgroups, median duration of response was 21.4 months (95% CI, 4.0–not estimable) and 3.5 months (95% CI, 2.8–8.3) and disease control rates were 56.7 and 28.3%, respectively. Median PFS in the 1 L-mn and 2 L subgroups was 2.8 months (95% CI, 2.3–4.1) and 1.4 months (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 11.1 months (95% CI, 8.9–13.7) and 6.6 months (95% CI, 5.4–9.4), respectively. In the 1 L-mn subgroup, median OS measured from start of 1 L chemotherapy was 18.7 months (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 grade ≥3 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.

Highlights

  • We evaluated the antitumor activity and safety of avelumab, a human anti–PD-L1 IgG1 antibody, as first-line switch-maintenance (1 First-line switch-maintenance (L-mn)) or second-line (2 L) treatment in patients with advanced gastric/gastroesophageal cancer (GC/Gastroesophageal junction cancer (GEJC)) previously treated with chemotherapy

  • In the 1 L-mn subgroup, median overall survival (OS) measured from start of 1 L chemotherapy was 18.7 months

  • In the 1 L-mn subgroup, 27.8% had achieved a partial response (PR) with prior chemotherapy; in the 2 L subgroup, prior responses were PR in 13.3% and complete response (CR) in 1.7%

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Summary

Introduction

We evaluated the antitumor activity and safety of avelumab, a human anti–PD-L1 IgG1 antibody, as first-line switch-maintenance (1 L-mn) or second-line (2 L) treatment in patients with advanced gastric/gastroesophageal cancer (GC/GEJC) previously treated with chemotherapy. First-line (1 L) standard of care for advanced inoperable GC/GEJC is based on combination fluoropyrimidine and platinum treatment, with trastuzumab added for HER2+ tumors. Maintenance therapy, ie, continued treatment with an agent administered in the 1 L induction regimen or sequential treatment with a different agent until progression (switch maintenance), has the potential to extend durations of response and OS, when an agent with a different mechanism of action is employed, while avoiding potential additive toxicity associated with further chemotherapy or combination treatment. The role of maintenance therapy in treating GC/GEJC is less well defined, observational and retrospective studies of maintenance fluoropyrimidine treatment in advanced GC/GEJC have shown that this approach is feasible and may improve progression-free survival (PFS) compared with observation alone [6,7,8]

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