Impact Of Somatic Mutations On Recurrence Free Survival (Rfs) And Overall Survival (Os) For Resected Nonsmall Cell Lung Cancer (Nsclc): Results From The Japan Molecular Epidemiology For Lung Cancer Study (Jme).

8549 Background: We previously reported molecular profiling as a primary endpoint in a prospective multicenter molecular epidemiology study, collecting 876 surgically resected NSCLC and examining 72-gene somatic mutation status using the next-generation sequencing (JME study; Kawaguchi T, J Clin Oncol 2016). The secondary endpoint was OS and RFS analysis (UMIN 000008177). Here, we report follow-up data and clinical outcomes in the JME study and the impact of somatic mutations on RFS and OS. Methods: All the patients were enrolled from July 2012 to December 2013, and clinical and prognostic data were obtained until the end of November 2017. Cox proportional hazards model were applied to assess the impact of the gene mutations on RFS and OS, considering gender, smoking history, age, stage, histology, history of adjuvant chemotherapy, EGFR, KRAS, TP53, and number of coexisting mutations. Results: Median follow up time was 48.4 months, and 876 patients were analyzed: 419 were men; 734 were non-squamous carcinoma; 441 had smoking history; 450 were ≥70 years; 618/131/127 were stage I/II/III-IV, 309 received the adjuvant chemotherapy. Among these, 141 had ≥ two somatic mutations. Multivariate analysis showed the number of coexisting mutations (≥2 vs. 0 or 1, HR = 1.643, 95%CI: 1.126-2.373), age (≥70 vs. < 70, HR = 1.561, 95%CI: 1.201-2.035) and pathological stage (II vs. I, HR = 3.103, 95%CI: 2.217-4.304; ≥III vs. I, HR = 6.382, 95%CI: 4.641-8.758) were significantly associated with RFS, while in OS, EGFR mutations (yes vs. no, HR = 0.450, 95%CI: 0.277-0.715), adjuvant chemotherapy (yes vs. no, HR = 0.493, 95%CI: 1.406-2.967), age (≥70 vs. < 70, HR = 1.694, 95%CI: 1.201-2.415) and pathological stage (II vs. I, HR = 2.448, 95%CI: 1.581-3.723; ≥III vs. I, HR = 6.601, 95%CI: 4.498-9.665) were also significant prognostic factors. Conclusions: Our prospective study showed less number of coexisting mutations, earlier stage and younger age were associated with longer RFS, while in OS, EGFR mutation and adjuvant chemotherapy were significantly associated with improved OS as well as earlier stage and younger age in resected NSCLC.