PAZEC: a Dutch Gynaecological Oncology Group open-label, multicenter, phase II study of pazopanib in metastatic and locally advanced hormone-resistant endometrial cancer

Anneke Westermann; Petronella Ottevanger; An Reyners; Judith R Kroep; Martijn G H Van Oijen; Roy Lalisang; Petronella O Witteveen

doi:10.1136/ijgc-2023-004781

PAZEC: a Dutch Gynaecological Oncology Group open-label, multicenter, phase II study of pazopanib in metastatic and locally advanced hormone-resistant endometrial cancer

Int J Gynecol Cancer. 2024 Jan 6:ijgc-2023-004781. doi: 10.1136/ijgc-2023-004781. Online ahead of print.

Authors

Anneke Westermann¹, Petronella Ottevanger², An Reyners³, Judith R Kroep⁴, Martijn G H Van Oijen⁵, Roy Lalisang⁶, Petronella O Witteveen⁷

Affiliations

¹ Department of Medical Oncology, Amsterdam University Medical Centers, Amsterdam, The Netherlands a.m.westermann@amsterdamumc.nl.
² Dutch Gynaecological Oncology Group (DGOG) and Department of Medical Oncology, Radboud University Medical Center, Nijmegen, The Netherlands.
³ University Medical Center Groningen (UMCG), Groningen, The Netherlands.
⁴ DGOG and Department of Medical Oncology, Leiden University Medical Center (LUMC), Leiden, The Netherlands.
⁵ Department of Medical Oncology, Cancer Center Amsterdam, Amsterdam, The Netherlands.
⁶ Internal Medicine/Medical Oncology, Maastricht University Medical Centre+, Maastricht, The Netherlands.
⁷ Department of Oncology, University Medical Center, Utrecht, The Netherlands.

PMID: 38184318
DOI: 10.1136/ijgc-2023-004781

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.

Keywords: Endometrial Neoplasms; Endometrium.