Effects of Co-occurring Genomic Alterations on Outcomes in Patients with KRAS -Mutant Non-Small Cell Lung Cancer

• Published in: Clinical cancer research Vol. 24; no. 2; pp. 334 - 340
• Main Authors: Arbour, Kathryn C, Jordan, Emmett, Kim, Hyunjae Ryan, Dienstag, Jordan, Yu, Helena A, Sanchez-Vega, Francisco, Lito, Piro, Berger, Michael, Solit, David B, Hellmann, Matthew, Kris, Mark G, Rudin, Charles M, Ni, Ai, Arcila, Maria, Ladanyi, Marc, Riely, Gregory J
• Format: Journal Article
• Language: English
• Published: United States American Association for Cancer Research Inc 15.01.2018
• Subjects: Adenocarcinoma; Cancer; Chemotherapy; Confidence intervals; Experimental design; Immune checkpoint inhibitors; K-Ras protein; Lung cancer; Lungs; Multivariate analysis; Mutation; Non-small cell lung carcinoma; p53 Protein; Patients; Platinum; Survival
• ISSN: 1078-0432; 1557-3265
• DOI: 10.1158/1078-0432.CCR-17-1841

mutations occur in approximately 25% of patients with non-small cell lung cancer (NSCLC). Despite the uniform presence of mutations, patients with -mutant NSCLC can have a heterogeneous clinical course. As the pattern of co-occurring mutations may describe different biological subsets of patients with -mutant lung adenocarcinoma, we explored the effects of co-occurring mutations on patient outcomes and response to therapy. We identified patients with advanced -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. Among 330 patients with advanced -mutant lung cancers, the most frequent co-mutations were found in (42%), (29%), and / (27%). In a multivariate analysis, there was a significantly shorter survival in patients with co-mutations in / [HR, 1.96; 95% confidence interval (CI), 1.33-2.92; ≤ 0.001]. (HR, 1.3; = 0.22) and (HR 1.11, = 0.58) co-mutation statuses were not associated with survival. Co-mutation in / was also associated with shorter duration of initial chemotherapy (HR, 1.64; 95% CI, 1.04-2.59; = 0.03) and shorter overall survival from initiation of immune therapy (HR, 3.54; 95% CI, 1.55-8.11; = 0.003). Among people with -mutant advanced NSCLC, , and / are the most commonly co-occurring somatic genomic alterations. Co-mutation of and / is an independent prognostic factor, predicting shorter survival, duration of response to initial platinum-based chemotherapy, and survival from the start of immune therapy. .