Targeting mTOR pathway in gynecological malignancies: Biological rationale and systematic review of published data

- mTOR inhibitors are becoming widely used in gynecological cancers.
- mTOR inhibitors can achieve relevant clinical benefit in advanced gynecological cancers.
- The toxicity of mTOR inhibitors can limit its use specially in combination with chemotherapy or bevacizumab.
- Results of ongoing trials with new generations of PI3K/mTOR inhibitors are eagerly awaited.

BackgroundmTOR inhibitors are widely used in different malignancies with several trials testing their efficacy and safety in gynecological malignancies. We aimed to review the current evidence that support the expansion of using such drugs in the treatment of advanced gynecological cancers.MethodsA comprehensive systematic review of literature has been conducted to include prospective trials that used everolimus, temsirolimus or ridaforolimus in the management of gynecological cancers and have available efficacy and toxicity results.ResultsA total of 23 studies including 980 patients were considered eligible for our review. Our review included 16 phase II and 7 phase I studies with the majority of patients having uterine cancers. Regarding Endometrial cancer, the CBR ranged from 21% to 60% and median PFS from 2.8 months to 7.3 months. In Ovarian cancers, CBR ranged from 24% to 50% and median PFS from 3.2 months to 5.9 months. In the single phase II study in cervical cancer the CBR was 61% and median PFS was 3.5 months. The toxicity profile was consistent with what was observed previously in other malignancies with fatigue, mucositis, and hematological toxicities being the most common adverse events observed.ConclusionmTOR inhibitors seem to be a promising option in the second line management of advanced gynecological cancers with best safety and efficacy outcomes when given as a single agent or in combination with hormonal treatment. More research is needed for better patient selection.