Poster Presentation COSA 2015 ASM

Phase 3, randomized trial (CheckMate 017) of nivolumab (Nivo) vs docetaxel in advanced squamous (SQ) cell non-small cell lung cancer (NSCLC) (#214)

Karen Reckamp 1 , David R Spigel 2 , Naiyer Rizvi 3 , Elena Poddubskaya 4 , Howard West 5 , Wilfried Eberhardt 6 , Paul Baas 7 , Scott J Antonia 8 , Adam Pluzanski 9 , Everett E Vokes 10 , Esther Holgado 11 , David Waterhouse 12 , Neal Reddy 13 , Justin Gainor 14 , Osvaldo Arén Frontera 15 , Leora Horn 16 , Luis Paz-Ares 17 , Jin Zhu 18 , Mark Lynch 18 , Julie Brahmer 19
  1. City of Hope Comprehensive Cancer Center, Duarte, CA, USA
  2. Sarah Cannon Research Institute/Tennessee Oncology, PLLC, Nashville, TN, USA
  3. Memorial Sloan-Kettering Cancer Centre, New York, NY, USA
  4. N.N. Blokhin Russian Cancer Research Center, Moscow, Russian Federation
  5. Swedish Cancer Institute, Seattle, WA, USA
  6. University Hospital Essen, West German Cancer Center, University Duisburg-Essen , Ruhrlandklinik, Germany
  7. The Netherlands Cancer Institute, Amsterdam, Netherlands
  8. H. Lee Moffitt Cancer Centre & Research Institute, Tampa, FL, USA
  9. Centrum Onkologii - Instytut Im. Marii Sklodowskiej-Curie, Warsaw, Poland
  10. University of Chicago Medicine & Biological Sciences, Chicago, IL, USA
  11. Hospital De Madrid, Norte Sanchinarro, Spain
  12. Oncology Hematology Care, Cincinnati, OH, USA
  13. Duke University Medical Centre, Durham, NC, USA
  14. Massachusetts General Hospital Cancer Center, Boston, MA, USA
  15. Centro Internacional de Estudios Clinicos, Santiago, Chile
  16. Vanderbilt University Medical Center, Nashville, TN, USA
  17. Hospital Universitario Virgen Del Rocio, Sevilla, Spain
  18. Bristol-Myers Squibb, Princeton, NJ, USA
  19. The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD, USA

Aim: We report results from a randomized, open-label, phase 3 study comparing nivolumab vs docetaxel in patients with previously treated squamous NSCLC and disease progression during/after 1 prior platinum-doublet chemotherapy regimen.

Methods: Patients (N=272) were randomized 1:1 to nivolumab 3 mg/kg Q2W (n=135) or docetaxel 75 mg/m2 Q3W (n=137) until disease progression or discontinuation due to toxicity/other reasons. For nivolumab patients, treatment after initial progression was permitted at the investigator’s discretion, per protocol. Primary objective was overall survival (OS). Secondary objectives included investigator-assessed overall response rate (ORR; per RECIST v1.1), progression-free survival (PFS), efficacy by programmed death ligand-1 (PD-L1) expression (PD-L1 testing not required for enrollment), patient-reported outcomes, and safety.

Results: Nivolumab led to 41% reduction in risk of death (hazard ratio [HR]=0.59; 95% CI: 0.44, 0.79; P=0.00025) and improved ORR (20% vs 9%; P=0.0083) and PFS (HR=0.62; 95% CI: 0.47, 0.81; P=0.0004) vs docetaxel. Twenty-eight patients were treated with nivolumab beyond initial progression; 9 demonstrated non-conventional patterns of benefit (ie, reduction in target lesions with simultaneous appearance of new lesions, initial progression followed by tumor reduction, or no further progression for ≥2 tumor assessments). Tumor PD-L1 expression of 1%, 5%, or 10% was neither prognostic nor predictive of benefit. OS HRs favored nivolumab across most predefined patient subgroups; 7% (9/131) of nivolumab and 55% (71/129) of docetaxel patients experienced grade 3–4 drug-related adverse events (AEs). No deaths were related to nivolumab vs 3 docetaxel-related deaths.

Conclusions: CheckMate 017 achieved its primary objective, with nivolumab demonstrating clinically superior and statistically significant OS vs docetaxel in patients with advanced, previously treated, squamous NSCLC. Benefit was seen regardless of PD-L1 status. The safety profile of nivolumab is favorable vs docetaxel and consistent with prior studies. AEs were manageable with established guidelines. Nivolumab represents a new standard of care in these patients.