For a study, researchers sought to evaluate the impact of tumor mutational burden (TMB) status on the outcomes of first-line pembrolizumab treatment versus chemotherapy in KEYNOTE-062. They investigated the correlations between TMB (continuous variable; square root scale) assessed with FoundationOne CDx and clinical outcomes using logistic (ORR) and Cox proportional hazards (PFS, OS) regression models (objective response rate [ORR], progression-free survival [PFS], and overall survival [OS]). The clinical utility of TMB was assessed using the preset threshold of 10 mut/Mb. TMB data were available for 306 of 763 patients (40.1%; pembrolizumab, 107; pembrolizumab+chemotherapy, 100; chemotherapy, 99). TMB was significantly linked with clinical outcomes for patients receiving pembrolizumab or pembrolizumab in combination with chemotherapy (ORR, PFS, and OS; all P<0.05) but not for those receiving chemotherapy (all P>0.05). Overall, 16% of patients had TMB greater than or equal to 10 mut/Mb, and 44% of those patients had malignancies with notable microsatellite instability (MSI-H). Better clinical outcomes (ORR, PFS, and OS) were observed in patients treated with pembrolizumab (pembrolizumab monotherapy and pembrolizumab+chemotherapy) who had TMB greater than 10 mut/Mb. The therapeutic value of pembrolizumab (with or without chemotherapy) in comparison to chemotherapy by the TMB cutoff and the favorable correlation between clinical results with pembrolizumab or pembrolizumab+chemotherapy and TMB as a continuous variable were attenuated. An exploratory analysis of KEYNOTE-062 suggests a connection between TMB and clinical efficacy with first-line pembrolizumab-based therapy in patients with advanced gastric/gastroesophageal junction cancer. The removal of MSI-H cancer patients did, however, reduce the therapeutic effectiveness of TMB.

Source: aacrjournals.org/clincancerres/article-abstract/28/16/3489/707386/Association-of-Tumor-Mutational-Burden-with?redirectedFrom=fulltext