Effects of co-occurring genomic alterations on outcomes in patients with KRAS-mutant non-small cell lung cancer

Background: KRAS mutations occur in approximately 25% of patients with non-small cell lung cancer (NSCLC).  Despite the uniform presence of KRAS mutations, patients with KRAS-mutant NSCLC can have a heterogeneous clinical course. Since the pattern of co-occurring mutations may describe different biological subsets of patients with KRAS-mutant lung adenocarcinoma, we explored the effects of co-occurring mutations on patient outcomes and response to therapy. Methods: We identified patients with advanced KRAS-mutant NSCLC and evaluated the most common co-occurring genomic alterations. Multivariate analyses were performed incorporating the most frequent co-mutations and clinical characteristics to evaluate association with overall survival as well as response to platinum-pemetrexed chemotherapy and immune checkpoint inhibitors. Results: Among 330 patients with advanced KRAS-mutant lung cancers, the most frequent comutations were found in TP53 (42%), STK11 (29%), and KEAP1/NFE2L2 (27%). In a multivariate analysis, there was a significantly shorter survival in patients with co-mutations in KEAP1/NFE2L2 (HR 1.96, 95%CI 1.33-2.92, p=<0.001). STK11 (HR1.3, p=0.22) and TP53 (HR 1.11, p= 0.58) co-mutation status were not associated with survival. Co-mutation in KEAP1/NFE2L2 was also associated with shorter duration of initial chemotherapy (HR 1.64, 95% CI 1.04-2.59, p=0.03) and shorter overall survival from initiation of immune therapy (HR 3.54, 95% CI 1.55-8.11, p=0.003). Conclusions: Among people with KRAS-mutant advanced NSCLC, TP53, STK11, and KEAP1/NFE2L2 are the most commonly co-occurring somatic genomic alterations. Comutation of KRAS and KEAP1/ NFE2L2 is an independent prognostic factor, predicting shorter survival, duration of response to initial platinum based chemotherapy, and survival from start of immune therapy.

from Cancer via ola Kala on Inoreader http://ift.tt/2ijBaKG
via IFTTT