First-line nivolumab plus platinum chemotherapy and bevacizumab for advanced nonsquamous non-small cell lung cancer: A 3-year follow-up of the phase 3 randomized TASUKI-52 trial

Objectives: In the randomized phase III TASUKI-52 trial, nivolumab with carboplatin, paclitaxel, and bevacizumab significantly prolonged the progression-free survival (PFS) of treatment-naive patients with advanced or recurrent nonsquamous non-small cell lung cancer (NSCLC). Here, we report the long-term outcomes of patients treated with nivolumab plus carboplatin, paclitaxel, and bevacizumab with 3 years of follow-up. Methods: Patients with stage IIIB/IV or recurrent nonsquamous NSCLC without sensitizing EGFR, ALK, or ROS1 mutations were randomized (1:1) to receive either nivolumab or placebo, in addition to carboplatin, paclitaxel, and bevacizumab, every 3 weeks. Treatment was continued for a maximum of six cycles. The endpoints included PFS, overall survival (OS), and safety. Exploratory analyses included efficacy and safety in subgroups. Results: A total of 550 patients were randomized to the nivolumab arm (n = 275) and placebo arm (n = 275). At the minimum follow-up of 36.1 months, PFS was consistently longer in the nivolumab arm than in the placebo arm (median, 10.6 vs. 8.2 months; hazard ratio [HR], 0.59; 95 % confidence interval [CI], 0.47–0.73; P < 0.0001), with PFS rates of 20.2 % vs. 4.9 %. The median OS was 31.6 months (95 % CI, 26.8–36.5) in the nivolumab arm and 24.7 months (95 % CI, 21.1–28.0) in the placebo arm (HR, 0.71; 95 % CI, 0.57–0.88), with OS rates of 44.2 % and 32.3 %, respectively. Of note, PFS and OS favored the nivolumab arm across patients with different PD-L1 expression levels, and regardless of baseline brain metastasis status. Grade 3–4 treatment-related adverse events occurred in 76.2 % and 74.9 % of the patients in the nivolumab and placebo arms, respectively, while no new safety concerns were identified. Conclusion: Nivolumab, in addition to carboplatin, paclitaxel, and bevacizumab, remained to demonstrate significantly longer PFS and long-term OS benefit compared with placebo in the first-line treatment of patients with nonsquamous NSCLC. The extended follow-up identified no new safety signals.