European Cancer Congress (ECC) 2015
Presented by the European Society for Medical Oncology
ECC 2015. Abstract 3010. Phase 3, randomized trial (CheckMate 057) of nivolumab (NIVO) vs docetaxel (DOC) in advanced non-squamous (non-SQ) non-small cell lung cancer (NSCLC): Subgroup analyses and patient reported outcomes (PROs)
L. Horn et al. (USA)
Background: Treatment options are limited for patients (pts) with advanced non-SQ NSCLC who progress after platinum-based doublet chemotherapy (PT-DC). DOC is approved for second-line treatment of advanced NSCLC; however, no single agent therapy has shown superior survival and improved tolerability vs DOC in this setting. We report results from a randomized, global phase 3 study of NIVO, a fully human IgG4 programmed death-1 (PD-1) immune checkpoint inhibitor antibody, vs DOC in pts with advanced non-SQ NSCLC after failure of PT-DC and tyrosine kinase inhibitor, if eligible.
Methods: Pts were randomized to NIVO 3mg/kg Q2W (n=292) or DOC 75mg/m2 Q3W (n=290) until progression or discontinuation due to toxicity/other reasons. Primary objective was OS; secondary objectives were investigator-assessed ORR (per RECIST v1.1), PFS, efficacy by PD-L1 expression, PROs, and safety.
Results: NIVO improved OS (hazard ratio [HR]=0.73; 96% CI: 0.59, 0.89; P=0.00155) (figure1) and ORR (19.2% vs 12.4%; P=0.0235) vs DOC. HR for PFS was 0.92 (95%CI: 0.77, 1.11; P=0.393) (Table 1). Grade 3–5 treatment-related adverse events (AEs) occurred in 10.5% (30/287) of NIVO and 53.7% (144/268) of DOC pts. Treatment-related serious AEs (SAEs) were less frequent in the NIVO arm. Treatment-related AEs leading to discontinuation (DC) were more common with DOC vs NIVO (Table 2). No deaths were related to NIVO vs 1 DOC-related death. Additional subgroup analyses, including efficacy by tumor PD-L1 expression, and PROs, will be presented.
Figure 1. Overall Survival.
Table 1. Efficacy measures
Table 2. Treatment-related adverse events (AE)
Figure 2. Change in LCSS ASBI (on-treatment)
Conclusions: NIVO significantly improved OS vs DOC in pts with advanced, previously-treated non-SQ NSCLC. The safety profile of NIVO 3mg/kg Q2W was favorable vs DOC. NIVO demonstrated survival benefit across histologies in two randomized phase 3 trials.
CARE Faculty Canadian Perspective:
Nivolumab a PD-1 monoclonal antibody has already been approved in NSLCL squamous cell histology in second-line therapy. Checkmate 057 was performed in non-squamous histology. Nivolumab was well tolerated with few (10.5%) grade 3-5 toxicity and less than 4% discontinuing treatment because of these toxicities.
Quality of life was presented and was surprisingly not superior at 12 weeks, a secondary endpoint. However, this reflects a flaw in design as quality of life in responding patients was seen beyond twelve weeks up to a year. It is unusual for quality of life to go up or stay up for extended periods of time with drug exposure. This is unique with the PD-1 checkpoint inhibitors and reflects their positive side effect profile.
- CARE Oncology Faculty