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Abstract
Objective There is a continued need for improvement of second-line systemic treatment for metastatic and/or recurrent endometrial cancer.
Methods In this phase II, open-label study, eligible patients had histologically or cytologically confirmed endometrial cancer, 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. The primary endpoint was progression-free survival at 3 months, with secondary outcomes of overall response rate, progression-free survival, overall survival, and toxicity. The study was powered to demonstrate 50% progression-free survival at 3 months with α=0.05 and β=80%.
Results Between January 2011 and February 2016, 60 eligible patients were included (intention-to-treat population). Median age was 68 (range, 53–85) years. Previous treatment included pelvic radiotherapy (58%), chemotherapy (90%), and hormonal therapy (43%). Three-month progression-free survival was 63.3% in the intention-to-treat population, with median progression-free survival and overall survival of 3.4 and 7.5 months, respectively. Overall response rate was 8.3%, and median follow-up 7.6 months. The most common grade 3 or higher adverse events were gastrointestinal toxicity in 21% of participants, including two patients with a gut perforation, one fatal gastrointestinal hemorrhage, one enterocutaneous fistula, and one fatal enterovaginal fistula. Extensive peritoneal disease existed in 80% of the patients with severe gastrointestinal toxicity. A definite correlation with previous radiotherapy could not be established.
Conclusions Pazopanib met its primary endpoint of 3 months’ progression-free survival in advanced endometrial cancer (63.3%), but response rates were modest. There may be a correlation for rare but severe gastrointestinal toxicity with previous treatments and/or disease site that has yet to be elucidated.
- Endometrium
- Endometrial Neoplasms
Data availability statement
Data are available upon reasonable request.
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Data availability statement
Data are available upon reasonable request.
Footnotes
Contributors AW: guarantor, conceptualization, data curation, formal analysis, funding acquisition, investigation, methodology, project administration, resources, supervision, validation, visualization, writing - original draft, writing - review and editing. PO: conceptualization, funding acquisition, investigation, methodology, project administration, resources, writing - review and editing. AR: conceptualization, investigation, methodology, resources, writing - review and editing. JRK: conceptualization, funding acquisition, investigation, methodology, resources, writing - review and editing. MGHVO: data curation, formal analysis, validation, visualization, writing - review and editing. RL: conceptualization, funding acquisition, investigation, methodology, resources, writing - review and editing. POW: conceptualization, funding acquisition, investigation, methodology, resources, writing - review and editing.
Funding This work was supported by Novartis.
Competing interests None declared.
Provenance and peer review Not commissioned; externally peer reviewed.
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