Effect of metformin on recurrence-free survival and overall survival in diabetic patients affected by advanced ovarian cancer.

Abstract

5522^ Background: Metformin, has recently shown some anti-cancer activities in ovarian cancer, both in vitro and in vivo. Methods: Analysis of Recurrence Free Survival (RFS) and Overall Survival (OS) was performed in patients (pts) with diabetes (D) treated with metformin (DMet+) or not (DMet-) enrolled in the MIMOSA trial, a randomized double-blind placebo-controlled international trial of Abagovomab maintenance therapy in 888 pts with advanced ovarian cancer. In the MIMOSA trial, no differences in the RFS and OS were observed between Abagovomab (n = 593) and Placebo arm (n = 295); hence, the present RFS and OS analysis (DMet+ vs DMet-) was run regardless of treatment allocation. A Cox proportional hazards model was used for adjusting the analysis for the predefined prognostic factors: Figo stage (III, IV), tumor size after debulking (residual tumor <1 cm, >1cm); CA125 serum level after 3th cycle (<35U/ml, >35U/ml). In addition, comparison of RFS and OS was done between DMet+and the overall MIMOSA population not exposed to metformin (ALLMet-), and between the overall diabetic pts (ALLD+) and non-diabetic pts (ALLD-). Results: In the ALL population (n = 888), 42 pts were affected by diabetes (ALLD+) divided to DMet+ (n = 27) and DMet- (n = 15), without difference in the prognostic factors distribution. When analysis was done in ALLD+, RFS median time was not reached in the DMet+ group whereas it was 328 days [CI: 30-660] in DMet- group with HR favoring DMet+=0.419 [CI:0.175-1.002]; p = 0.05. Median OS time was also not reached in the DMet+ group whereas it was 786 days [CI:262-NE] in DMet- group with HR=0.295 [CI:0.109-0.803]; p = 0.02. Interestingly HR for RFS time was still in favour of DMet+ group when compared to the ALLMet- (n=861) with HR=0.575 (CI=0.324-1.022); p = 0.06. When ALLD+ were compared with ALLD-(n = 846), no significant differences was detected in RFS and OS time. Conclusions: The present results are the first prospectively analyzed data demonstrating a favourable impact of metformin treatment on RFS and OS in pts affected by advanced ovarian cancer. Clinical trial information: NCT00418574.