Overview
The clinical relevance of tumor mutational burden (TMB) as a biomarker for predicting the efficacy of immunotherapy in cancer treatment has been a subject of ongoing research and debate. The KEYNOTE 158 trial, led to the FDA approval of the FoundationOneCDx assay as a companion diagnostic (CDx) for single-agent pembrolizumab for the treatment of patients with unresectable or metastatic TMB-high (TMB-H) [≥10 mutations/megabase (mut/Mb)] solid tumors.
Researchers of this study further explored the clinical validity of TMB measurement using the FoundationOneCDx test across a diverse cohort of over 8,000 patients spanning 24 cancer types, all treated with single-agent immune checkpoint inhibitors (ICIs). By leveraging a large, real-world dataset, from the US-based deidentified Flatiron Health (FH)-Foundation Medicine (FMI) solid tumor and pantumor Clinico-Genomic Databases with clinical data from the FH Research Database linked to genomic data derived from FMI comprehensive genomic profiling tests, this research found elevated TMB levels were significantly associated with improved real-world overall survival (rwOS) in patients receiving anti-PD-(L)1 monotherapy. This association was consistent across various cancer types and particularly pronounced in patients with TMB levels ≥10 mut/Mb, confirming the threshold set by the KEYNOTE 158 trial.
Why this matters
As immunotherapy becomes more widely used in cancer treatment, finding reliable ways to predict which patients will benefit is crucial. This large real-world study provides strong evidence that the FDA-approved TMB test can help identify patients who may benefit from immunotherapy across multiple cancer types. By validating TMB's predictive value in a real-world context, this research contributes to the evolving landscape of personalized medicine, where biomarkers like TMB could play a crucial role in optimizing cancer treatment strategies and improving patient outcomes.