DURHAM, NC — Non-small-cell lung cancer (NSCLC) patients showed significant benefit from the use of immune checkpoint inhibitors (ICIs) in a study looking at use of the therapy for five major cancer types in the VA healthcare system.
The study from the VA’s National Oncology Program, the Durham, NC, VAMC and Duke University Department of Medicine noted that ICIs “are used for an increasing number of indications across various tumor types, as well as several tumor-agnostic indications in patients with advanced cancer. Although many patients benefit from ICI therapy, others do not, highlighting a need for better predictive biomarkers.”
The report in JCO Precision Oncology explained that tumor mutational burden (TMB) “reflects the global number of mutations within a tumor and has been widely explored as a predictive biomarker of ICI response. The current tumor type-agnostic U. S. Food and Drug Administration approval of pembrolizumab for metastatic solid tumors defines high TMB (TMB-H) as ≥10 mut/Mb as measured by FoundationOne CDx. This fixed cutoff may not be the ideal value across all solid tumors.”
The study team performed a retrospective analysis of the association of survival outcomes with TMB in patients treated with ICI for five major cancer types – NSCLC, head and neck (H&N), urothelial, melanoma or esophageal/gastric — using real-world data from the VA.
Results indicated that overall survival (OS) was significantly longer for patients with TMB-H vs. TMB low tumors in NSCLC (n = 1,593), head and neck (H&N) cancer (n = 222), and urothelial cancer (n = 332). On the other hand, overall survival was not significantly different based on TMB status in melanoma (n = 207) or esophageal/gastric cancer (n = 248).
“Consistent with previous studies, a predictive value of TMB ≥10 mut/Mb for ICI response was found in NSCLC and H&N, but not in esophageal/gastric cancer,” the authors wrote. “Although inconclusive in the literature, significant association was found in urothelial cancer. The predictive value of TMB in melanoma was inconclusive. Our analysis does not support the use of a fixed threshold for TMB as a standalone predictive biomarker for ICI across all solid tumors.”
- Scobie MR, Zhou KI, Ahmed S, Kelley MJ. Utility of Tumor Mutational Burden as a Biomarker for Response to Immune Checkpoint Inhibition in the VA Population. JCO Precis Oncol. 2023 Sep;7:e2300176. doi: 10.1200/PO.23.00176. PMID: 38039430.
