Nivolumab Versus Docetaxel in Previously Treated Patients With Advanced Non-Small-Cell Lung Cancer: Two-Year Outcomes From Two Randomized, Open-Label, Phase III Trials (CheckMate 017 and CheckMate 057)

Abstract

Purpose Nivolumab, a programmed death-1 inhibitor, prolonged overall survival compared with docetaxel in two independent phase III studies in previously treated patients with advanced squamous (CheckMate 017; ClinicalTrials.gov identifier: NCT01642004) or nonsquamous (CheckMate 057; ClinicalTrials.gov identifier: NCT01673867) non-small-cell lung cancer (NSCLC). We report updated results, including a pooled analysis of the two studies. Methods Patients with stage IIIB/IV squamous (N = 272) or nonsquamous (N = 582) NSCLC and disease progression during or after prior platinum-based chemotherapy were randomly assigned 1:1 to nivolumab (3 mg/kg every 2 weeks) or docetaxel (75 mg/m² every 3 weeks). Minimum follow-up for survival was 24.2 months. Results Two-year overall survival rates with nivolumab versus docetaxel were 23% (95% CI, 16% to 30%) versus 8% (95% CI, 4% to 13%) in squamous NSCLC and 29% (95% CI, 24% to 34%) versus 16% (95% CI, 12% to 20%) in nonsquamous NSCLC; relative reductions in the risk of death with nivolumab versus docetaxel remained similar to those reported in the primary analyses. Durable responses were observed with nivolumab; 10 (37%) of 27 confirmed responders with squamous NSCLC and 19 (34%) of 56 with nonsquamous NSCLC had ongoing responses after 2 years' minimum follow-up. No patient in either docetaxel group had an ongoing response. In the pooled analysis, the relative reduction in the risk of death with nivolumab versus docetaxel was 28% (hazard ratio, 0.72; 95% CI, 0.62 to 0.84), and rates of treatment-related adverse events were lower with nivolumab than with docetaxel (any grade, 68% v 88%; grade 3 to 4, 10% v 55%). Conclusion Nivolumab provides long-term clinical benefit and a favorable tolerability profile compared with docetaxel in previously treated patients with advanced NSCLC.

Fig 1.

CONSORT diagram of disposition of patients with (A) squamous non–small-cell lung cancer (NSCLC) or (B) nonsquamous NSCLC.

Fig 2.

Kaplan-Meier curves of (A and B) overall survival (OS) and (C and D) progression-free survival (PFS; investigator assessed) in patients with (A and C) squamous non–small-cell lung cancer (NSCLC) or (B and D) nonsquamous NSCLC. (*) Not calculable (NC) because no patients continued with follow-up for progression at this time point; the PFS rate at the time of the last event was 3%, and the last observation at 2 years was not an event.

Fig 3.

Swimmer plots that show time to first response and duration of response (per Response Evaluation Criteria in Solid Tumors [RECIST] version 1.1) for responders with (A) squamous non–small-cell lung cancer (NSCLC) treated with nivolumab, (B) squamous NSCLC treated with docetaxel, (C) nonsquamous NSCLC treated with nivolumab, and (D) nonsquamous NSCLC treated with docetaxel.

Fig 4.

Treatment effect on overall survival (OS) by best overall response. (*) Confirmed complete and partial response per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 as assessed by the investigator. (†) Includes death before disease assessment, never treated, early discontinuation because of toxicity, and other. HR, hazard ratio; NR, not reached; NSCLC, non–small-cell lung cancer.

Fig 5.

Efficacy according to programmed death ligand-1 (PD-L1) expression. Two-year overall survival (OS) rates by PD-L1 expression level in patients with (A) squamous non–small-cell lung cancer (NSCLC) and (B) nonsquamous NSCLC and (C) treatment effect on OS by PD-L1 expression (pooled analysis of patients with squamous and nonsquamous NSCLC). (*) All patients include those with no quantifiable PD-L1 expression (CheckMate 017, nivolumab [n = 18; docetaxel, n = 29]; CheckMate 057, nivolumab [n = 61; docetaxel, n = 66]). (†) Hazard ratios (HRs) shown are for overall OS on the basis of 2 years' minimum follow-up.

Fig 6.

(A) Treatment-related adverse events (AEs) reported in ≥ 10% of patients and (B) time to onset of first treatment-related select AE in patients treated with nivolumab (pooled patients with squamous and nonsquamous non–small-cell lung cancer [NSCLC]). (*) Patients with one or more select AEs from first dose until 30 days post-treatment in a given category were counted only once in the time interval corresponding to the first event; patients with multiple events from different categories within the same time interval were counted once in each category. (†) Of the 11 patients with a first AE > 12 months after initiating treatment, one was skin related (grade 2), three were GI related (grade 1 [n = 1] and grade 2 [n = 2]), one was endocrine related (grade 1), three were hepatic related (grade 1 [n = 2] and grade 2 [n = 1]), and three were pulmonary related (grade 1 [n = 1] and grade 2 [n = 2]).