TY - JOUR
T1 - PAZEC
T2 - a Dutch Gynaecological Oncology Group open-label, multicenter, phase II study of pazopanib in metastatic and locally advanced hormone-resistant endometrial cancer
AU - Westermann, Anneke
AU - Ottevanger, Petronella
AU - Reyners, An
AU - Kroep, Judith R
AU - Van Oijen, Martijn G H
AU - Lalisang, Roy
AU - Witteveen, Petronella O
PY - 2024/1/6
Y1 - 2024/1/6
N2 - 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 a=0.05?and ß=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.
AB - 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 a=0.05?and ß=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.
KW - Endometrial Neoplasms
KW - Endometrium
U2 - 10.1136/ijgc-2023-004781
DO - 10.1136/ijgc-2023-004781
M3 - Article
SN - 1048-891X
VL - 34
JO - International Journal of Gynecological Cancer
JF - International Journal of Gynecological Cancer
IS - 2
ER -