The following article features coverage from the Society of Gynecologic Oncology 2020 meeting. Click here to read more of Cancer Therapy Advisor‘s conference coverage.

Results of an interim analysis from a phase 3 study evaluating metformin vs placebo — both in combination with platinum-based chemotherapy — in women with advanced endometrial cancer showed no significant difference in overall survival (OS) between the 2 study arms. These findings were accepted for presentation at the Society of Gynecologic Oncology (SGO) Annual Meeting on Women’s Cancer and released on March 28, 2020.1

Early clinical investigations of metformin, an oral antidiabetic drug, have shown promise in the setting of advanced endometrial cancer.2

Biologic rationales for metformin as a cancer therapy include reductions in insulin resistance and glucose associated with its use. Furthermore, metformin has been shown to activate AMP-activated kinase (AMPK), which is involved in the inhibition of synthetic metabolic pathways that consume ATP.  Because the risk of endometrial cancer is increased in patients with hyperinsulinemia, hyperglycemia, and obesity, patients with this cancer type were considered good candidates for evaluation of the potential anticancer effects of metformin.2

In this randomized, placebo-controlled, double-blind, phase 2/3 clinical trial from the Gynecologic Oncology Group (ClinicalTrials.gov Identifier: NCT02065687), patients with stage III, IV, or recurrent endometrial cancer were randomly assigned to receive initial therapy with up to 10 cycles of paclitaxel plus carboplatin chemotherapy in combination with 850 mg of metformin or placebo administered twice daily, followed by maintenance therapy with metformin or placebo depending on study arm assignment, until disease progression. Primary study endpoints were progression-free survival (PFS) and overall survival (OS) in the phase 2 and phase 3 portions of the study, respectively.


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Although an analysis of the phase 2 trial results supported continued investigation of the combination of metformin with chemotherapy in the phase 3 portion of the study, an interim analysis of the data for 469 patients at a median follow-up of 28 months showed median OS was 30 months for patients receiving placebo compared with 35 months for those treated with metformin (hazard ratio [HR], 0.886; 95% CI, 0.676-1.161; P =.185).

Furthermore, comparisons of the PFS and objective response rates for patients in the 2 study arms also showed no significant differences, and body mass index was not a predictor of benefit from metformin-containing therapy.

In their concluding comments, the study authors noted that additional translational studies are under way “to identify potential biomarkers of endometrial cancer patients that may have benefited from metformin treatment.”

Read more of Cancer Therapy Advisor‘s coverage of SGO 2020 by visiting the conference page.

References

  1. Bae-Jump VL, Sill M, Gehrig PA, et al. A randomized phase II/III study of paclitaxel/carboplatin/metformin versus paclitaxel/carboplatin/placebo as initial therapy for measureable stage III or IVA, stage IVB, or  recurrent endometrial cancer. Submitted to: Society of Gynecologic Oncology (SGO) 2020 Annual Meeting on Women’s Cancer. Abstract 11.
  2. Lee TY, Martinez-Outschoorn UE, Schilder RJ, et al. Metformin as a therapeutic target in endometrial cancers. Front Oncol. 2018;8:4-14.