Tumor mutational burden and survival on immune checkpoint inhibition in >8000 patients across 24 cancer types

作者：David R. Gandara, Neeraj Agarwal, Shilpa Gupta, Samuel Jacob Klempner, Miles Cameron Andrews, Amit Mahipal, Vivek Subbiah, Ramez Nassef Eskander, David Paul Carbone, Jonathan Wesley Riess, Sarah LeNoir Sammons, Jeremy Williams Snider, Lilia Bouzit, Cheryl D. Cho-Phan, Megan M. Price, Gerald Li, Júlia C.F. Quintanilha, Richard S.P. Huang, Jeffrey S. Ross, David A. Fabrizio, Geoffrey R. Oxnard, Ryon P. Graf · 发表于：Journal for ImmunoTherapy of Cancer · 年份：2025 · DOI：10.1136/jitc-2024-010311 · 被引用次数：57 · 研究领域：Cancer Immunotherapy and Biomarkers、Lung Cancer Diagnosis and Treatment、Inflammatory Biomarkers in Disease Prognosis

BACKGROUND: There is uncertainty around clinical applicability of tumor mutational burden (TMB) across cancer types, in part because of inconsistency between TMB measurements from different platforms. The KEYNOTE 158 trial supported United States Food and Drug Administration (FDA) approval of the Foundation Medicine test (FoundationOneCDx) at TMB≥10 mut/Mb as a companion diagnostic (CDx) for single-agent pembrolizumab in second+line. Using a large real-world dataset with validated survival endpoint data, we evaluated clinical validity of TMB measurement by the test in over 8000 patients across 24 cancer types who received single-agent immune checkpoint inhibitor (ICI). METHODS: Patients with advanced-stage cancers from 24 cancer types treated with single-agent anti-PD(L)1 therapy in standard-of-care settings were included. Deidentified data from electronic health records from approximately 280 cancer treatment facilities were captured into a clinico-genomic database. This study used the TMB algorithm from the FDA-approved test supporting solid tumor CDx and composite mortality variable validated against the national death index: real-world overall survival (rwOS). Following a prespecified analysis plan, rwOS by TMB level was assessed using Cox PH models adjusted for Eastern Cooperative Oncology Group performance status, prior treatment, microsatellite instability, sex, age, opioid rx pretherapy, and socioeconomic assessment. RESULTS: 8440 patients met inclusion criteria. Adju...