Metformin for patients with advanced stage ovarian cancer: A randomized phase II placebo-controlled trial

Objective

The primary aim of this study was to determine if metformin, an oral biguanide administered with first-line chemotherapy and continued as maintenance therapy, improves progression-free survival (PFS) for patients with advanced-stage ovarian cancer.

Methods

Patients with pathologically confirmed advanced-stage ovarian cancer undergoing primary debulking or neoadjuvant platinum-based chemotherapy followed by surgery were eligible to participate. Patients were randomized 1:1 to receive platinum/taxane-based chemotherapy with metformin 850 mg orally twice per day or placebo, followed by maintenance therapy (metformin or placebo) for two years from the date of randomization.

Results

108 evaluable patients were enrolled; 54 were randomly assigned to metformin, and 54 to placebo. Sixty-six percent (n = 71) received neoadjuvant therapy, 31 % (n = 33) primary debulking surgery, and 88 % (n = 93) had tumors of high-grade serous histology. The primary endpoint, PFS, was not significantly different between the treatment groups (1-sided p-value = 0.31; adjusted hazard ratio [HR] = 0.87, 95 % confidence interval [CI]: 0.56–1.36). Median PFS was 15.4 months (95 % CI: 11.2–23,5) for metformin and 14.3 months (95 % CI: 11.6–18.0) for placebo. Overall survival (OS) was not significantly different (2-sided p-value = 0.21; adjusted HR = 1.49, 95 % CI: 0.86–2.59), with a median of 40.7 months (95 % CI: 28.0–48.2) for metformin versus 43.8 months (95 % CI: 35.3–57.2) for placebo. The addition of metformin was well tolerated, and there were no differences in toxicity between the two groups.

Conclusion

Although it was well-tolerated, adding metformin to first-line platinum/taxane-based therapy does not improve PFS or OS for patients with newly diagnosed advanced stage ovarian cancer.