**2. Nivolumab in Clinical Trials**

The CheckMate 057 trial was designed for patients with non-squamous NSCLC. Eligible patients had primary CS IIIB/IV NSCLC or recurrent NSCLC after radiation therapy or surgical resection and documented disease progression during or after one platinum-based doublet chemotherapy regimen [3]. Patients with an acceptable general condition and adequate organ function without major comorbidities were included [3]. In all, 582 patients were randomized: 292 were assigned to receive nivolumab at a dose of 3 mg/kg every 2 weeks, and 290 to receive docetaxel at a dose of 75 mg/m2 every 3 weeks. OS was the primary endpoint. The key secondary endpoints were investigator-assessed confirmed objective response rate and progression-free survival (PFS). Tumor response was assessed with the use of the Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST 1.1), at week 9 and then every 6 weeks until disease progression. Safety was assessed with the Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE), version 4.0.

The median OS was longer in the nivolumab group than in the docetaxel group (12.2 months, 95% confidence interval (CI) 9.7–15.0, versus 9.4 months, 95% CI 8.1–10.7; hazard ratio (HR) 0.73, 95% CI 0.59–0.89; *p* = 0.002). The objective response rate was 19% with nivolumab versus 12% with docetaxel (*p* = 0.02). Treatment-related adverse events (AEs) of any grade were reported in 69% of patients in the nivolumab group and in 88% in the docetaxel group, while grade 3–4 AEs occurred in 10% of the nivolumab group and in 54% of the docetaxel group [3]. The most important data from that study are presented in Table 1.

**Table 1.** Nivolumab for previously treated non-small-cell lung cancer—CheckMate 017/057 [2,3].


HR—hazard ratio, ORR—overall response rate, PFS—progression-free survival, OS—overall survival, AE—adverse event.

The CheckMate 017 trial was designed for patients with squamous NSCLC. Eligible patients had CS IIIB/IV NSCLC and documented disease progression after one platinum-based doublet chemotherapy [4]. The main inclusion or exclusion criteria and treatment outline were similar to those for the CheckMate 057 trial. In all, 272 patients underwent randomization: 135 patients were assigned to receive nivolumab and 137 to receive docetaxel [4].

The median OS was longer with nivolumab than with docetaxel (9.2 months, 95% CI 7.3–13.3, versus 6.0 months, 95% CI 5.1–7.3; HR 0.59, 95% CI 0.44–0.79; *p* < 0.001). The response rate was 20% with nivolumab versus 9% with docetaxel (*p* = 0.008). Treatment-related AEs of any grade occurred in 58% of patients in the nivolumab group and in 86% in the docetaxel group. Grade 3–4 AEs occurred in 7% of the nivolumab group and in 55% of the docetaxel group. The most important data from that study are presented in Table 1.

A pooled analysis of long-term outcomes confirmed the efficacy of nivolumab [4,5]. The 4-year OS rate was 14% in patients treated with nivolumab, compared with 5% in patients treated with docetaxel (14.9% for patients with non-squamous NSCLC and 9.4% for patients with squamous NSCLC in the nivolumab population); the 5-year OS rate was 13.4% with nivolumab versus 2.6% with docetaxel (HR 0.68, 95% CI 0.59–0.78) [4,5]. Patients in the nivolumab group who achieved an objective response had the best long-term results. Median OS in patients with an objective response was not reached in the nivolumab group (95% CI 25.6–not reached) versus 17.1 months (95% CI 11.1–28.7) in the docetaxel group. The 4-year OS rate in patients with an objective response was 58% with nivolumab and 12% with docetaxel [4].
