Phase 2 trial of avelumab in combination with gemcitabine in advanced leiomyosarcoma as a second-line treatment (EAGLES, Korean Cancer Study Group UN18-09).

Abstract

In this single-arm, multicenter, phase 2 trial, the authors evaluated the efficacy and safety of avelumab plus gemcitabine in patients with leiomyosarcoma (LMS) who failed on first-line chemotherapy. Patients with advanced LMS received avelumab 10 mg/kg on days 1 and 15 (for up to 24 months) plus gemcitabine 1000 mg/m² on days 1, 8, and 15 of a 28-day cycle until they developed disease progression or intolerable toxicity. The primary end point was the objective response rate (ORR). In total, 38 patients were enrolled. Of these, 35 patients were evaluable, and the ORR was 20% (95% confidence interval; [CI], 8%-37%). The disease control rate was 71%, and the median duration of response was 21.8 months (range, 7.6 to ≥43.3 months). The median progression free-survival was 5.6 months (95% CI, 4.5-6.8 months), and the median overall survival was 27.5 months (95% CI, 20.4-34.6 months). Grade 3-4 adverse events occurred in 70% of patients, of which neutropenia was the most common (54%). Immune-mediated adverse events occurred in five patients (14%; hypothyroidism, n = 3; hepatitis, n = 2). Patients who had a higher density of tumor-infiltrating lymphocytes (greater than the median) exhibited better ORR (35% vs. 8%; p = .104), progression-free survival (median, 7.3 vs. 3.3 months; p = .024), and overall survival (median, not reached vs. 21.5 months; p = .027). The combination of avelumab and gemcitabine demonstrated promising efficacy and manageable safety in patients with advanced LMS who progressed on first-line therapy. Tumor-infiltrating lymphocyte density may be an important factor in predicting the response to combining immunotherapy with chemotherapy.