Tumor Mutational Burden and Efficacy of Nivolumab Monotherapy and in Combination with Ipilimumab in Small-Cell Lung Cancer

Matthew D. Hellmann, Margaret K. Callahan, Mark M. Awad, Emiliano Calvo, Paolo A. Ascierto, Akin Atmaca, Naiyer A. Rizvi, Fred R. Hirsch, Giovanni Selvaggi, Joseph D. Szustakowski, Ariella Sasson, Ryan Golhar, Patrik Vitazka, Han Chang, William J. Geese, Scott J. Antonia

Research output: Contribution to journalArticlepeer-review

Abstract

Durable responses and encouraging survival have been demonstrated with immune checkpoint inhibitors in small-cell lung cancer (SCLC), but predictive markers are unknown. We used whole exome sequencing to evaluate the impact of tumor mutational burden on efficacy of nivolumab monotherapy or combined with ipilimumab in patients with SCLC from the nonrandomized or randomized cohorts of CheckMate 032. Patients received nivolumab (3 mg/kg every 2 weeks) or nivolumab plus ipilimumab (1 mg/kg plus 3 mg/kg every 3 weeks for four cycles, followed by nivolumab 3 mg/kg every 2 weeks). Efficacy of nivolumab ± ipilimumab was enhanced in patients with high tumor mutational burden. Nivolumab plus ipilimumab appeared to provide a greater clinical benefit than nivolumab monotherapy in the high tumor mutational burden tertile. Hellmann et al. evaluate the impact of tumor mutational burden on the efficacy of nivolumab monotherapy or combination with ipilimumab in patients with small-cell lung cancer (SCLC). They show that treatment efficacy and the increased benefit of the combination are most substantial in SCLC with high tumor mutational burden.

Original languageEnglish
JournalCancer Cell
DOIs
Publication statusPublished - Jan 1 2018

Keywords

  • biomarkers
  • clinical trial
  • CTLA-4
  • immunotherapy
  • ipilimumab
  • nivolumab
  • PD-1
  • small cell lung cancer
  • tumor mutation burden

ASJC Scopus subject areas

  • Oncology
  • Cell Biology
  • Cancer Research

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