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Among 330 patients whose lung cancer carried a mutated KRAS gene, the ones who also had a broken KEAP1 gene did worse on every treatment: chemotherapy stopped working sooner and immunotherapy barely worked at all.
Patients with advanced KRAS-mutant non-small-cell lung cancer were identified and their most common co-occurring genomic alterations evaluated, with multivariate analyses of association with overall survival, response to platinum and pemetrexed chemotherapy and response to immune checkpoint inhibitors. Among 330 patients, the most frequent co-mutations were TP53 (42%), STK11 (29%) and KEAP1 or NFE2L2 (27%). In multivariate analysis, co-mutation in KEAP1 or NFE2L2 carried significantly shorter survival (hazard ratio 1.96), while STK11 (1.3) and TP53 (1.11) co-mutation status were not associated with survival. KEAP1 or NFE2L2 co-mutation was also associated with a shorter duration of initial chemotherapy (hazard ratio 1.64) and shorter overall survival from the start of immune therapy (3.54).
It separated the prognostic co-mutation, KEAP1, from the predictive one, STK11, in a disease where the two are often quoted together, and it is the reason KEAP1 status is worth reading off a report even though no treatment depends on it.
Shares STK11 / KEAP1 co-mutations, STK11 or KEAP1 loss in KRAS-mutant lung adenocarcinoma, KEAP1-NRF2 antioxidant pathway, KEAP1.
Shares Gregory J. Riely, STK11 / KEAP1 co-mutations, KEAP1, STK11.
Shares STK11 / KEAP1 co-mutations, STK11 or KEAP1 loss in KRAS-mutant lung adenocarcinoma, KEAP1, KRAS G12C.
Shares STK11 / KEAP1 co-mutations, KEAP1-NRF2 antioxidant pathway, KEAP1, STK11.
Shares Gregory J. Riely, STK11 / KEAP1 co-mutations, KEAP1, STK11.
Shares STK11 / KEAP1 co-mutations, STK11 or KEAP1 loss in KRAS-mutant lung adenocarcinoma, KEAP1, STK11.
Shares STK11 / KEAP1 co-mutations, STK11 or KEAP1 loss in KRAS-mutant lung adenocarcinoma, KEAP1, STK11.
Shares STK11 / KEAP1 co-mutations, STK11, Memorial Sloan Kettering Cancer Center, Comprehensive genomic profiling.