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

2018; Cell Press; Volume: 33; Issue: 5 Linguagem: Inglês

10.1016/j.ccell.2018.04.001

1878-3686

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, Chang Han, William J. Geese, Scott Antonia,

Lung Cancer Treatments and Mutations

Summary 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.