Durvalumab in Patients With Treatment-Naive Stage IV NSCLC With an ECOG Performance Status of 2 to 3 and High PD-L1 Tumor Expression (IFCT-1802 SAVIMMUNE): A Multicenter Phase 2 Trial

Introduction Eastern Cooperative Oncology Group performance status 2 to 3 is associated with poor survival and chemotherapy-related adverse events (AEs). The impact of poor PS on the safety and efficacy of immune checkpoint inhibitors has not been elucidated. This study aimed to assess first-line durvalumab in patients with PS 2 to 3 with advanced NSCLC and high programmed cell death-ligand 1 (PD-L1) expression. Methods In this single-arm, prospective, multicenter, phase II trial, patients with PS 2 to 3 aged 18 to 75 years with metastatic NSCLC and PD-L1 tumor proportion score more than or equal to 25% received durvalumab until progression or toxicity. Primary end point was safety, that is incidence of grade more than or equal to 3 TRAEs during the first 8 weeks. Secondary end points included blinded independent central review overall response rate, progression-free survival, duration of response, overall survival (OS), and PS improvement at 8 weeks and health-related quality of life. Results A total of 50 patients were enrolled. Median follow-up was 26.2 (19.9–35.2) months. Prevalence of grade more than or equal to 3 TRAEs during the first 8 weeks was 10.0% (five of 50, 95% confidence interval [CI] 1.7–18.3), and no grade 5 occurred. Overall response rate at 8 weeks was 26% (95% CI 13.8–38.2). Median duration of response, progression-free survival, and OS were 11.8 months (95% CI, 7.2-not reached), 2.3 months (95% CI 1.7–5.6), and 7.1 months (95% CI 3.9–14.5), respectively. The 12-month OS rate was 40% (95% CI 26.5–53.1). Median OS in patients with PS 2 and PS 3 was 11.4 (95% CI 4.4–32.8) and 3.0 (95% CI 0.2–5.6) months, respectively. Of 27 patients, 12 (44.4%) still receiving durvalumab at 8 weeks had improved PS ( p = 0.0096). Mean global QLQ-C30 score significantly increased at 8 weeks. Conclusions In patients with a PS of 2 to 3 with advanced NSCLC and high PD-L1 expression, first-line durvalumab was safe with 40% 1-year OS.