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/m 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.

Anti-Angiogenics: Their Value in Lung Cancer Therapy

“…Throughout all studies, a greater OS benefit was seen in non-sq NSCLC patients with higher PD-L1 expression [42][43][44][45]. However treatment benefits including long durable responses were also seen in patients with PD-L1 < 1% [46]. In the first 3 months, more patients with non-sq carcinoma died in the nivolumab arm than in the docetaxel arm [42].…”

“…Although the numbers of patients with EGFR mutations included in trials with PD-(L)1 inhibitors in stage IV disease were relatively low, their outcomes suggest that immune checkpoint inhibition is not beneficial in these patients [44][45][46]. Evidence implies that AAT on the other hand may have an additional benefit in this subgroup in combination with EGFR TKIs [33,37].…”

Multimodal Anti-tumor Approaches Combined with Immunotherapy to Overcome Tumor Resistance in Esophageal and Gastric Cancer

“…In non-small cell lung cancer (NSCLC) and melanoma, immuno-checkpoint inhibitors have markedly improved patient prognosis and have led to a major change in clinical practice guidelines (13)(14)(15)(16)(17)(18)(19). In gastrointestinal malignancies, tumor-targeted immuno-response has been identified as relevant prognostic parameter and potential therapeutic target (20,21).…”

Personalized therapy for lung cancer: Striking a moving target

“…These developments have completely altered the treatment landscape for patients with NSCLC. Other inhibitors of the PD-1 pathway such as nivolumab and atezolizumab have also demonstrated improved outcomes for patients with advanced-stage NSCLC (131,132). Another emerging novel approach for treatment of cancer includes combinations of immune checkpoint inhibitors.…”