A DGOG open-label multicenter phase II study of pazopanib in metastatic and locally advanced hormone-resistant endometrial cancer

Abstract

Background and Aims: We studied the effect of pazopanib on progression free survival (PFS) at three months in metastatic, recurrent and/or locally advanced endometrial cancer. Methods: Eligible patients had histologically or cytologically confirmed AEC, documented progressive disease and a WHO performance status of < 2. All participants received treatment with pazopanib 800 mg once daily until progression, unacceptable toxicity or patient refusal. Patients were evaluable for the primary endpoint of PFS at three months if they had received pazopanib for at least four weeks. All participants were analysed for toxicity. The study was powered to demonstrate 50% PFS at 3 months (vs <30% based on previously reported studies) with alpha = 0.05 and beta = 80%. Results: Sixty patients were included from 2011‐2016, with a median age of 68. Previous treatment included pelvic radiotherapy (58%), chemotherapy (90%) and hormonal therapy (43%). Forty‐five out of sixty patients were evaluable for the primary endpoint. Twenty‐six participants (58%) had no progression at three months, with median PFS and OS of 5.3 and 9.5 months, respectively. The most common SAE were gastrointestinal in 21% of 60 participants, including 2 patients with a gut perforation, one fatal gastrointestinal hemorrhage, one enterocutaneous fistula and one fatal enterovaginal fistula. Peritoneal disease existed in 80% of patients with severe gastrointestinal toxicity. A definite correlation with previous radiotherapy could not be established. Conclusions: Pazopanib showed encouraging 3 months PFS in AEC. There may be a correlation between previous treatments and/or disease site with rare but severe gastrointestinal toxicity that has yet to be elucidated.