Relationship between metformin use and recurrence and survival in patients (pts) with resected stage III colon cancer (CC) receiving adjuvant chemotherapy: Results from NCCTG N0147 (Alliance).

3531 Background: Although preclinical and epidemiological data suggest that metformin may have antineoplastic properties in CC, the impact of metformin use on pt survival in stage III CC undergoing curative resection is unknown. Methods: Before randomization to FOLFOX +/- cetuximab, 1958 stage III CC pts enrolled on N0147 study completed a questionnaire that included information on diabetes mellitus (DM) and metformin use. Cox models assessed the association between metformin use and outcomes of disease free survival (DFS), overall survival (OS) and time to recurrence (TTR), adjusting for clinical/pathological factors. Results: 1691 (86%), 115 (6%) and 152 (8%) of 1958 pts reported no history of DM, DM with metformin use, or DM with no metformin use, respectively. The two treatment arms were pooled since metformin use showed homogeneous effects on outcomes across arms. There was no difference in DFS, OS and TTR irrespective of metformin use when DM pts were compared to non-DM pts, after adjusting for tumor/pt factors (Table). Within the cohort of DM pts (n = 267), DFS (HR = 0.90; 95% CI: 0.59-1.35; p = 0.595), OS (HR = 0.99; 95% CI: 0.65-1.49; p = 0.948) and TTR (HR = 0.87; 95% CI: 0.56-1.35; p = 0.534) were similar in metformin users compared to non-users. Survival outcomes were comparable regardless of duration of metformin use ( < 1, 1-5, 6-10, 11+ years) before randomization (p = 0.361 for DFS; p = 0.068 for OS). There were no interaction effects observed between metformin use and clinical/pathological factors (KRAS, BRAF mutation status, tumor site, T/N stage, gender, and age). Conclusions: Stage III CC patients treated with adjuvant chemotherapy who used metformin experienced similar DFS, OS, or TTR compared to non-DM pts or DM pts without metformin use. Group DFS OS TTR HR (95% CI) p value HR (95% CI) p value HR (95% CI) p value Non-DM Ref Ref Ref DM, metformin use 0.95 (0.67-1.36) 0.796 1.17 (0.82-1.67) 0.383 0.91 (0.62-1.33) 0.616 DM, no metformin use 1.15 (0.86-1.54) 0.361 1.26 (0.93-1.72) 0.138 1.14 (0.84-1.57) 0.401