Posted: Friday, December 9, 2022
Based on the results of an analysis, which were presented at the 2022 Society for Immunotherapy of Cancer (SITC) Annual Meeting (Abstract 29) and published in the Journal for ImmunoTherapy of Cancer, a composite signature extending beyond tumor mutational burden and PD-L1 identified patients with non–small cell lung cancer (NSCLC) benefiting from immune checkpoint inhibitor therapy more effectively than single biomarkers. David R. Gandara, MD, of the University of California Davis Cancer Center, Sacramento, and colleagues suggested this signature may be used to inform treatment selection. A large phase III trial is ongoing to validate these findings.
The investigators focused on patients with squamous cell lung cancer from the Lung Master Protocol (Lung-MAP) substudies S1400A (n = 68; durvalumab) and S1400I (n = 252; nivolumab with or without ipilimumab) who had tissue comprehensive genomic profiling data. Despite the associations observed between tumor mutational burden and ARID1A mutations (P = .009), PD-L1 and KEAP1/NFE2L2 mutations (P = .007), and ARID1A mutations and KEAP1/NFE2L2 mutations (odds ratio = 2.89; P = .0016), the investigators found the magnitude of correlation to be “modest,” thus representing complementary predictors. Higher tumor mutational burden (> 20 vs. 10–20 vs. 0–9) appeared to be the most significant positive predictor of overall survival (hazard ratio [HR] = 0.79; P = .01).
A composite combinatorial signature for immune checkpoint inhibitor efficacy, which included tumor mutational burden, PD-L1, HLA loss of heterozygosity, ARID1A, and KEAP1/NFE2L2 mutations, was found to be associated with better overall (HR = 0.76; P = .005) and progression-free (HR = 0.84; P = .048) survival outcomes. The landmark 3-year overall survival rates were 29% and 6% in the immune checkpoint inhibitor signature–high and –low groups, respectively. A total of 39% of the evaluable population was classified into the immune checkpoint inhibitor signature–high group.
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