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Invited Commentary
April 9, 2020

The Mystic Role of Tumor Mutational Burden in Selecting Patients With Lung Cancer for First-Line Immunotherapy

Author Affiliations
  • 1Division of Oncology, Department of Medicine, Washington University School of Medicine, St Louis, MO
JAMA Oncol. 2020;6(5):674-675. doi:10.1001/jamaoncol.2020.0264

Recent advances in our understanding of the biologic characteristics of tumors and the cancer immunity cycle have led to an important shift in the standard-of-care treatment for metastatic non–small cell lung cancer (NSCLC). First-line platinum-based doublet chemotherapy was established as the standard of care about 2 decades ago and has served as the yardstick for comparing incremental benefits afforded by emerging treatments. This dogma changed with the approval of first-line single-agent anti–programmed cell death 1 (PD-1) therapy, and subsequently anti–PD-1 therapy in combination with platinum-based doublet chemotherapy ushered in a new standard of care: immunotherapy with or without chemotherapy.1,2 Nivolumab in combination with ipilimumab was the first anti–PD-1 and anti–cytotoxic T-lymphocyte–associated antigen 4 (CTLA-4) therapy to show a progression-free survival (PFS) advantage compared with platinum-based chemotherapy in patients with a high tumor mutational burden (TMB), with a 1-year PFS of 42.6% with nivolumab and ipilimumab vs 13.2% with chemotherapy, as shown in the CheckMate 2273 study. In addition, CheckMate 227 met its other coprimary end point of improved overall survival (OS) with nivolumab and ipilimumab (median OS, 17.1 months) compared with chemotherapy (14.9 months) in patients with programmed cell death ligand 1 (PD-L1) expression of 1% or greater.4

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