TY - JOUR
T1 - Phase II Trial of Cabozantinib in Recurrent/Metastatic Endometrial Cancer
T2 - A Study of the Princess Margaret, Chicago, and California Consortia (NCI9322/PHL86)
AU - Dhani, Neesha C.
AU - Hirte, Hal W.
AU - Wang, Lisa
AU - Burnier, Julia V.
AU - Jain, Angela
AU - Butler, Marcus O.
AU - Welch, Stephen
AU - Fleming, Gini F.
AU - Hurteau, Jean
AU - Matsuo, Koji
AU - Matei, Daniela
AU - Jimenez, Waldo
AU - Johnston, Carolyn
AU - Cristea, Mihaela
AU - Tonkin, Katia
AU - Ghatage, Prafull
AU - Lheureux, Stephanie
AU - Mehta, Anjali
AU - Quintos, Judy
AU - Tan, Qian
AU - Kamel-Reid, Suzanne
AU - Ludkovski, Olga
AU - Tsao, Ming Sound
AU - Wright, John J.
AU - Oza, Amit M.
N1 - Funding Information:
This study was supported by funding through N01 Phase II consortium contract (HHS N261201100032C). Correlative studies were funded through an Ontario Institute of Cancer Research Translational Research Team grant. The authors would also like to gratefully acknowledge the contributions of Dr. Swati Garg, Princess Margaret Cancer Centre, toward genomic analyses.
Funding Information:
funding from Ontario Institute of Cancer Research and Princess Margaret Cancer Centre Foundation.
Funding Information:
H.W. Hirte reports receiving speakers bureau honoraria from AstraZeneca and Merck, and reports receiving other remuneration from Merck for expert testimony. M.O. Butler is an employee/paid consultant for Merck, Bristol-Myers Squibb, Novartis, Immunocore, and GlaxoSmithKline, and reports receiving commercial research grants from Takara. G.F. Fleming reports receiving commercial research grants from Merck, Genentech, Tesaro, Corcept, Eisai, Abbvie, Hoffman La Roche, Compugen, Incyte, 47 Inc., Syndax, Iovance, Syros, Astex, Sanofi, and Sermonix, reports receiving other commercial research support from Corcept, reports receiving speakers bureau honoraria from Curio Science/ Vaniam, and is an advisory board member/unpaid consultant for Abbvie and TTC Oncology. J. Hurteau is an employee/paid consultant for GlaxoSmithKline. K. Matsuo reports receiving speakers bureau honoraria from Chugai, and reports receiving other remuneration from Springer and VBL Therapeutics. D. Matei is an employee/paid consultant for Radius Inc., Roche, AstraZeneca, and Tesaro. M. Cristea is an employee/paid consultant for Abbvie and AstraZeneca, and reports receiving speakers bureau honoraria from AstraZeneca. S. Lheureux is an employee/paid consultant for AstraZeneca, and reports receiving speakers bureau honoraria from AstraZeneca, GlaxoSmithKline, Roche, and Merck. No potential conflicts of interest were disclosed by the other authors.
Publisher Copyright:
© 2020 American Association for Cancer Research.
PY - 2020/6/1
Y1 - 2020/6/1
N2 - Purpose: The relevance of the MET/hepatocyte growth factor pathway in endometrial cancer tumor biology supports the clinical evaluation of cabozantinib in this disease. Patients and Methods: PHL86/NCI#9322 (NCT01935934) is a single arm study that evaluated cabozantinib (60 mg once daily) in women with endometrial cancer with progression after chemotherapy. Coprimary endpoints were response rate and 12-week progression-free-survival (PFS). Patients with uncommon histology endometrial cancer (eg, carcinosarcoma and clear cell) were enrolled in a parallel exploratory cohort. Results: A total of 102 patients were accrued. Among 36 endometrioid histology patients, response rate was 14%, 12-week PFS rate was 67%, and median PFS was 4.8 months. In serous cohort of 34 patients, response rate was 12%, 12-week PFS was 56%, and median PFS was 4.0 months. In a separate cohort of 32 patients with uncommon histology endometrial cancer (including carcinosarcoma), response rate was 6% and 12-week PFS was 47%. Six patients were on treatment for >12 months, including two for >30 months. Common cabozantinib-related toxicities (>30% patients) included hypertension, fatigue, diarrhea, nausea, and hand–foot syndrome. Gastrointestinal fistula/perforation occurred in four of 70 (6%) patients with serous/endometrioid cancer and five of 32 (16%) patients in exploratory cohort. We observed increased frequency of responses with somatic CTNNB1 mutation [four partial responses (PRs) in 10 patients, median PFS 7.6 months] and concurrent KRAS and PTEN/PIK3CA mutations (three PRs in 12 patients, median PFS 5.9 months). Conclusions: Cabozantinib has activity in serous and endometrioid histology endometrial cancer. These results support further evaluation in genomically characterized patient cohorts.
AB - Purpose: The relevance of the MET/hepatocyte growth factor pathway in endometrial cancer tumor biology supports the clinical evaluation of cabozantinib in this disease. Patients and Methods: PHL86/NCI#9322 (NCT01935934) is a single arm study that evaluated cabozantinib (60 mg once daily) in women with endometrial cancer with progression after chemotherapy. Coprimary endpoints were response rate and 12-week progression-free-survival (PFS). Patients with uncommon histology endometrial cancer (eg, carcinosarcoma and clear cell) were enrolled in a parallel exploratory cohort. Results: A total of 102 patients were accrued. Among 36 endometrioid histology patients, response rate was 14%, 12-week PFS rate was 67%, and median PFS was 4.8 months. In serous cohort of 34 patients, response rate was 12%, 12-week PFS was 56%, and median PFS was 4.0 months. In a separate cohort of 32 patients with uncommon histology endometrial cancer (including carcinosarcoma), response rate was 6% and 12-week PFS was 47%. Six patients were on treatment for >12 months, including two for >30 months. Common cabozantinib-related toxicities (>30% patients) included hypertension, fatigue, diarrhea, nausea, and hand–foot syndrome. Gastrointestinal fistula/perforation occurred in four of 70 (6%) patients with serous/endometrioid cancer and five of 32 (16%) patients in exploratory cohort. We observed increased frequency of responses with somatic CTNNB1 mutation [four partial responses (PRs) in 10 patients, median PFS 7.6 months] and concurrent KRAS and PTEN/PIK3CA mutations (three PRs in 12 patients, median PFS 5.9 months). Conclusions: Cabozantinib has activity in serous and endometrioid histology endometrial cancer. These results support further evaluation in genomically characterized patient cohorts.
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U2 - 10.1158/1078-0432.CCR-19-2576
DO - 10.1158/1078-0432.CCR-19-2576
M3 - Article
C2 - 31992589
AN - SCOPUS:85085714861
VL - 26
SP - 2477
EP - 2486
JO - Clinical Cancer Research
JF - Clinical Cancer Research
SN - 1078-0432
IS - 11
ER -
