Checkmate 017: A Phase 3 Study of Nivolumab vs Docetaxel in Previously Treated Advanced or Metastatic Squamous Cell NSCLC
Treatment options are limited for patients with advanced squamous (SQ) NSCLC who fail platinum-based doublet chemotherapy (PT-DC).a In this presentation, Spigel and colleaguesb reported the results of a randomized, open-label, global phase 3 study of nivolumab (NIVO), a fully human IgG4 anti-PD-1 immune checkpoint inhibitor antibody, versus docetaxel (DOC) in patients with SQ NSCLC who had disease progression (PD) during or after one prior PT-DC regimen. A total of 272 patients were randomized 1:1 to receive NIVO 3 mg/kg (n = 135) every 2 weeks or DOC 75 mg/m2 (n = 137) every 3 weeks until disease progression or discontinuation due to toxicity. The primary objective was overall survival (OS). Secondary objectives included investigator-assessed objective response rate (ORR; by RECIST v1.1), progression-free survival (PFS), efficacy stratified by PD-L1 expression, quality of life, and safety.
Significantly improved mean OS was observed with NIVO versus DOC (9.2 months vs. 6.0 months; HR = 0.59; 95% CI: 0.44, 0.79; P = 0.00025). NIVO also improved mean PFS vs DOC (3.5 months vs. 2.8 months; HR = 0.62; 95% CI: 0.47, 0.81; P = 0.0004). ORR was 20% for NIVO and 9% for DOC (P = 0.0083). OS hazard ratios favored NIVO regardless of PD-L1 expression.; mean OS was higher with NIVO versus DOC in patients with PD-L1 levels at 1%, 5%, and 10% cut points. The average Symptom Burden Index was better in patients treated with NIVO compared with those receiving DOC. Grade 3–5 drug-related AEs occurred in 7% of NIVO and 57% of DOC pts. No deaths were related to NIVO versus 3 DOC-related deaths. The authors concluded that there was significantly superior OS with NIVO versus DOC in patients with advanced, previously treated SQ NSCLC and that NIVO also demonstrated PFS and ORR superiority over DOC. Tumor PD-L1 status was neither prognostic nor predictive for efficacy endpoints. The safety profile of NIVO 3 mg/kg Q2W was acceptable and favorable vs DOC. Thus, NIVO is the first PD-1 inhibitor to demonstrate an OS benefit versus standard of care in previously-treated patients with advanced SQ NSCLC and represents a significant improvement as second-line therapy for these patients. In a lively discussion of this presentation, it was suggested that in SQ NSCLC, where patients on DOC treatment do poorly, NIVO could be the best option as second-line therapy in this patient population.
- Ang YL, et al. Ther Adv Respir Dis. 2015;Apr 22 [Epub ahead or print].
- Spigel DR, et al. ASCO 2015. Abstract 8009.