Nivolumab versus Docetaxel in Advanced Squamous-Cell Non-Small-Cell Lung Cancer

Abstract

Background: Patients with advanced squamous-cell non-small-cell lung cancer (NSCLC) who have disease progression during or after first-line chemotherapy have limited treatment options. This randomized, open-label, international, phase 3 study evaluated the efficacy and safety of nivolumab, a fully human IgG4 programmed death 1 (PD-1) immune-checkpoint-inhibitor antibody, as compared with docetaxel in this patient population.

Methods: We randomly assigned 272 patients to receive nivolumab, at a dose of 3 mg per kilogram of body weight every 2 weeks, or docetaxel, at a dose of 75 mg per square meter of body-surface area every 3 weeks. The primary end point was overall survival.

Results: The median overall survival was 9.2 months (95% confidence interval [CI], 7.3 to 13.3) with nivolumab versus 6.0 months (95% CI, 5.1 to 7.3) with docetaxel. The risk of death was 41% lower with nivolumab than with docetaxel (hazard ratio, 0.59; 95% CI, 0.44 to 0.79; P<0.001). At 1 year, the overall survival rate was 42% (95% CI, 34 to 50) with nivolumab versus 24% (95% CI, 17 to 31) with docetaxel. The response rate was 20% with nivolumab versus 9% with docetaxel (P=0.008). The median progression-free survival was 3.5 months with nivolumab versus 2.8 months with docetaxel (hazard ratio for death or disease progression, 0.62; 95% CI, 0.47 to 0.81; P<0.001). The expression of the PD-1 ligand (PD-L1) was neither prognostic nor predictive of benefit. Treatment-related adverse events of grade 3 or 4 were reported in 7% of the patients in the nivolumab group as compared with 55% of those in the docetaxel group.

Conclusions: Among patients with advanced, previously treated squamous-cell NSCLC, overall survival, response rate, and progression-free survival were significantly better with nivolumab than with docetaxel, regardless of PD-L1 expression level. (Funded by Bristol-Myers Squibb; CheckMate 017 ClinicalTrials.gov number, NCT01642004.).

Figure 1. Kaplan–Meier Curves for Overall Survival

The analysis included all the patients who underwent randomization. Symbols indicate censored observations, and horizontal lines the rates of overall survival at 1 year.

Figure 2. Efficacy of Nivolumab versus Docetaxel in Patients with Advanced Squamous-Cell Non–Small-Cell Lung Cancer

Panel A shows the characteristics of response and disease progression as assessed by the investigator, according to the Response Evaluation Criteria in Solid Tumors, version 1.1. Bars indicate the duration of response. Arrows indicate ongoing response at the time of data censoring. Panel B shows the Kaplan–Meier curves for progression-free survival, defined as the time from randomization to the date of the first documented event of tumor progression, death, or last tumor assessment that could be evaluated (data-censoring date). The analysis included all the patients who underwent randomization. Symbols indicate censored observations, and the horizontal lines the rates of progression-free survival at 1 year. Panel C shows the plot of hazard ratios for death (in the analysis of overall survival) and death or disease progression (in the analysis of progression-free survival), according to the level of expression of the ligand for programmed death 1 (PD-L1) at baseline. The prespecified expression levels for the PD-L1 biomarker analysis were 1%, 5%, and 10% of cells in a section with at least 100 tumor cells that could be evaluated.