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Cancer Cell. 2018 May 14;33(5):853-861.e4. doi: 10.1016/j.ccell.2018.04.001. Epub 2018 May 3.

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

Author information

1
Thoracic Oncology Service, Division of Solid Tumor Oncology, Department of Medicine, Memorial Sloan Kettering Cancer Center, Weill Cornell Medical College, and Parker Center for Cancer Immunotherapy, 885 2nd Avenue, New York, NY 10017, USA. Electronic address: hellmanm@mskcc.org.
2
Thoracic Oncology Service, Division of Solid Tumor Oncology, Department of Medicine, Memorial Sloan Kettering Cancer Center, Weill Cornell Medical College, and Parker Center for Cancer Immunotherapy, 885 2nd Avenue, New York, NY 10017, USA.
3
Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
4
START Madrid, Centro Integral Oncológico Clara Campal, Medical Oncology Division, Hospital Universitario Madrid Norte Sanchinarro, Madrid 28050, Spain.
5
Unit of Melanoma, Cancer Immunotherapy and Innovative Therapy, Istituto Nazionale Tumori Fondazione G. Pascale, Naples 80131, Italy.
6
Department of Hematology and Oncology, Krankenhaus Nordwest, UCT-University Cancer Center, Frankfurt am Main 60488, Germany.
7
Division of Hematology and Oncology, Columbia University Medical Center, New York, NY 10032, USA.
8
Department of Medicine, Division of Medical Oncology, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.
9
Clinical Development, Bristol-Myers Squibb, Princeton, NJ 08648, USA.
10
Translational Medicine, Bristol-Myers Squibb, Princeton, NJ 08648, USA.
11
Department of Thoracic Oncology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL 33612, USA.

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.

KEYWORDS:

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

PMID:
29731394
PMCID:
PMC6750707
DOI:
10.1016/j.ccell.2018.04.001
[Indexed for MEDLINE]
Free PMC Article

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