Benoit You, MD, PhD, Centre Hospitalier Lyon-Sud, Saint-Genis-Laval, France, discusses the rationale behind and results of the ENDOLA trial (NCT02755844), a Phase I/II study evaluating a chemotherapy-free combination of olaparib, metronomic cyclophosphamide, and metformin in recurrent advanced or metastatic endometrial cancer (EC) patients. First-line treatment for EC is platinum-based chemotherapy but there are currently no defined, effective late-line therapies. The primary endpoint of non-progression at 10 weeks was reached with a rate of 61.5%. Median progression-free survival was 5.1 months. Metronomic cyclophosphamide regimen may enhance the effects of olaparib because it is an anti-angiogenic alkylating agent, and metformin may increase the anti-proliferative effects of olaparib because it downregulates IGF1R and PI3K-AKT-mTor pathways, which are commonly altered in EC. There was only one dose limiting toxicity (DLT) at a regimen of 300mg olaparib with 50mg metronomic cyclophosphamide and 50mg metformin per day. This interview took place at the American Association for Cancer Research Annual Meeting in New Orleans, LA.
