858PD - A DGOG open-label multicenter phase II study of pazopanib in metastatic and locally advanced hormone-resistant endometrial cancer

Abstract

There is a pressing need for second-line systemic treatment for metastatic, recurrent and/or locally advanced endometrial cancer (AEC) after hormonal therapy or chemotherapy. We studied the effect of the selective multi-targeted receptor tyrosine kinase inhibitor pazopanib on progression free survival (PFS) at three months for patients with AEC. In this prospective phase II open label study, patients were recruited from six oncology departments in the Netherlands. 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. Dose reductions for toxicity were allowed. 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 and overall survival (OS). The study was powered to demonstrate 50% PFS at 3 months (vs <30% based on previously reported studies) with &agr; = 0.05 and &bgr; = 80%. Between January 2011 and February 2016, 60 eligible patients were included. Median age was 68 years (range 53-85). Previous treatment included pelvic radiotherapy (58%), chemotherapy (90%) and hormonal therapy (43%). Forty-five out of sixty patients were treated for at least four weeks, and were thus evaluable for the primary endpoint. Twenty-six of the evaluable patients (58%) had no progression at three months, with median PFS and OS of 5.3 and 9.5 months, respectively. The most common severe adverse events were gastrointestinal toxicity 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. 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.