Each research step that reveals patterns of activity with targeted therapies in endometrial cancer—such as metformin and temsirolimus (Torisel)—brings the field closer to developing increasingly effective and better-tolerated regimens that improve upon historical treatment results and quality of life (QOL) outcomes, according to Pamela T. Soliman, MD, MPH.
Soliman and colleagues conducted a phase 1 trial (NCT01529593) investigating the combination of temsirolimus plus metformin in patients with advanced or recurrent endometrial cancer. Among 33 response-evaluable patients, 2 (6%) achieved an overall response; both were partial responses (PRs).1 Additionally, 13 patients (39%) had stable disease (SD), which lasted at least 4 months in 11 patients, translating to a clinical benefit rate of 39%.
Soliman : Temsirolimus is an mTOR inhibitor, [and approximately] 50% of patients with endometrial cancer have an abnormality in the PTEN/AKT pathway. One of the ways we’ve tried to treat endometrial cancer is by targeting some of those steps. We first conducted studies with mTOR inhibition approximately 20 years ago, and we recognize that mTOR inhibitors alone don’t have a lot of activity for cancer shrinkage, but combining them with other drugs can enhance [their anticancer effects]. Several different [mTOR inhibitor-based] combinations have been evaluated, but the rationale for including metformin [in the doublet] is that metformin also works in patients with insulin resistance, and one of the downstream effects of metformin is that it potentiates the same pathway [as temsirolimus] and can co-inhibit mTOR. Additionally, patients with endometrial cancer often have insulin resistance, so addressing that and increasing the uptake of insulin in the peripheral circulation may inhibit endometrial cancer.
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