Robert L Ferris1, George Blumenschein2, Jerome Fayette3, Joel Guigay4, A Dimitrios Colevas5, Lisa Licitra6, Kevin J Harrington7, Stefan Kasper8, Everett E Vokes9, Caroline Even10, Francis Worden11, Nabil F Saba12, Lara Carmen Iglesias Docampo13, Robert Haddad14, Tamara Rordorf15, Naomi Kiyota16, Makoto Tahara17, Mark Lynch18, Vijayvel Jayaprakash18, Li Li18, Maura L Gillison2. 1. University of Pittsburgh Medical Center Hillman Cancer Center, Pittsburgh, PA, USA. Electronic address: ferrisrl@upmc.edu. 2. MD Anderson Cancer Center, Houston, TX, USA. 3. Centre Leon Berard, Lyon, France. 4. Centre Antoine Lacassagne, FHU OncoAge, Université Côte d'Azur, Nice, France. 5. Stanford University, Stanford, CA, USA. 6. Fondazione IRCCS Istituto Nazionale dei Tumori and University of Milan, Milan, Italy. 7. Royal Marsden NHS Foundation Trust/The Institute of Cancer Research National Institute of Health Research Biomedical Research Centre, London, UK. 8. West German Cancer Center, University Hospital, Essen, Germany. 9. University of Chicago Medical Center, Chicago, IL, USA. 10. Gustave Roussy, Villejuif Cedex, France. 11. University of Michigan, Ann Arbor, MI, USA. 12. Winship Cancer Institute of Emory University, Atlanta, GA, USA. 13. Hospital Universitario 12 de Octubre, Madrid, Spain. 14. Dana-Farber/Harvard Cancer Center, Boston, MA, USA. 15. Universitätsspital Zurich, Zurich, Switzerland. 16. Kobe University Hospital, Kobe, Japan. 17. National Cancer Center Hospital East, Kashiwa, Japan. 18. Bristol-Myers Squibb, Princeton, NJ, USA.
Abstract
OBJECTIVES: We report 2-year results from CheckMate 141 to establish the long-term efficacy and safety profile of nivolumab and outcomes by tumor PD-L1 expression in patients with recurrent or metastatic (R/M),platinum-refractory squamous cell carcinoma of the head and neck (SCCHN). METHODS:Patients with R/M SCCHN with tumor progression/recurrence within 6 months of platinum therapy were randomized 2:1 to nivolumab 3 mg/kg every 2 weeks or investigator's choice (IC). Primary endpoint: overall survival (OS). Data cutoff: September 2017. RESULTS: With 24.2 months' minimum follow-up, nivolumab (n = 240) continued to improve OS vs IC (n = 121), hazard ratio (HR) = 0.68 (95% CI 0.54-0.86). Nivolumab nearly tripled the estimated 24-month OS rate (16.9%) vs IC (6.0%), and demonstrated OS benefit across patients with tumor PD-L1 expression ≥1% (HR [95% CI] = 0.55 [0.39-0.78]) and < 1% (HR [95% CI] = 0.73 [0.49-1.09]), and regardless of tumor HPV status. Estimated OS rates at 18, 24, and 30 months with nivolumab were consistent irrespective of PD-L1 expression (<1%/≥1%). In the nivolumab arm, there were no observed differences in baseline characteristics or safety profile between long-term survivors and the overall population. Grade 3-4 treatment-related adverse event rates were 15.3% and 36.9% for nivolumab and IC, respectively. CONCLUSION:Nivolumab significantly improved OS at the primary analysis and demonstrated prolonged OS benefit vs IC and maintenance of a manageable and consistent safety profile with 2-year follow-up. OS benefit was observed with nivolumab irrespective of PD-L1 expression and HPV status. (Clinicaltrials.gov: NCT02105636).
RCT Entities:
OBJECTIVES: We report 2-year results from CheckMate 141 to establish the long-term efficacy and safety profile of nivolumab and outcomes by tumorPD-L1 expression in patients with recurrent or metastatic (R/M),platinum-refractory squamous cell carcinoma of the head and neck (SCCHN). METHODS:Patients with R/M SCCHN with tumor progression/recurrence within 6 months of platinum therapy were randomized 2:1 to nivolumab 3 mg/kg every 2 weeks or investigator's choice (IC). Primary endpoint: overall survival (OS). Data cutoff: September 2017. RESULTS: With 24.2 months' minimum follow-up, nivolumab (n = 240) continued to improve OS vs IC (n = 121), hazard ratio (HR) = 0.68 (95% CI 0.54-0.86). Nivolumab nearly tripled the estimated 24-month OS rate (16.9%) vs IC (6.0%), and demonstrated OS benefit across patients with tumorPD-L1 expression ≥1% (HR [95% CI] = 0.55 [0.39-0.78]) and < 1% (HR [95% CI] = 0.73 [0.49-1.09]), and regardless of tumor HPV status. Estimated OS rates at 18, 24, and 30 months with nivolumab were consistent irrespective of PD-L1 expression (<1%/≥1%). In the nivolumab arm, there were no observed differences in baseline characteristics or safety profile between long-term survivors and the overall population. Grade 3-4 treatment-related adverse event rates were 15.3% and 36.9% for nivolumab and IC, respectively. CONCLUSION:Nivolumab significantly improved OS at the primary analysis and demonstrated prolonged OS benefit vs IC and maintenance of a manageable and consistent safety profile with 2-year follow-up. OS benefit was observed with nivolumab irrespective of PD-L1 expression and HPV status. (Clinicaltrials.gov: NCT02105636).
Keywords:
CD274 protein, human (PD-L1 Protein, Human); Carcinoma, squamous cell of head and neck; Clinical Trial, Phase III; Head and Neck Neoplasms; Immunotherapy; Nivolumab; Papillomaviridae (HPV, Human Papillomavirus Viruses); Programmed Cell Death 1 Receptor; Survival Analysis; Survivors (Long-term Survivors)
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