TY - JOUR
T1 - A randomized phase II study of cabozantinib versus weekly paclitaxel in the treatment of persistent or recurrent epithelial ovarian, fallopian tube or primary peritoneal cancer
T2 - An NRG Oncology/Gynecologic Oncology Group study
AU - Matulonis, Ursula A.
AU - Sill, Michael W.
AU - Makker, Vicky
AU - Mutch, David G.
AU - Carlson, Jay W.
AU - Darus, Christopher J.
AU - Mannel, Robert S.
AU - Bender, David P.
AU - Crane, Erin K.
AU - Aghajanian, Carol
N1 - Funding Information:
Dr. Ursula Matulonis received monies from Clearity Foundation and Ovarian Cancer Research Foundation for Board membership. She also served as a consultant and received monies from Merck, Fujifilm, Mersana, Geneos and Immunogen. She also served as a consultant for 2× Oncology, receiving no monies paid to herself. She has grants/grants pending from Merck for an investigator-initiated clinical trial. She received payment for development of education presentations from i3 Health. Dr. Vicki Makker received monies paid to her for consultancy from Eisai Pharmaceuticals, Merck Pharmaceuticals and Karyopharm. Dr. David Mutch received monies paid to him for consultancy from Tesaro. Dr. Robert Mannel served on the Advisory Board as a consultancy for Clovis and Tesaro, receiving monies paid to his institution. Dr. Carol Aghajanian served as Honorarium, Ad Boards for Tesaro, Mateon Therapeutics, Cerulean and ImmunoGen. She also served as Honorarium for Steering Committee Meeting for Mateon Therapeutics and Clovis. All other co-authors have no conflicts of interest to declare.
Funding Information:
This study was supported by National Cancer Institute grants to the Gynecologic Oncology Group Administrative Office (CA 27469), the Gynecologic Oncology Group Statistical and Data Center (CA 37517), NRG Oncology (1 U10 CA180822), NRG Operations (U10CA180868) and UG1CA189867 (NCORP). Dr. Matulonis is supported by the Breast Cancer Research Foundation. Drs. Aghajanian and Makker are supported in part by the MSK Cancer Center Support Grant P30 CA008748. The following NRG Oncology/Gynecologic Oncology Group member institutions participated in this study: Memorial Sloan Kettering Cancer Center, Washington University School of Medicine, Cancer Research for the Ozarks NCORP, Women and Infants Hospital, University of Oklahoma Health Sciences Center, University of Iowa Hospitals and Clinics, Carolinas Medical Center/Levine Cancer Institute, Rush University Medical Center, Fox Chase Cancer Center, University of Wisconsin Hospital and Clinics, Fred Hutchinson Cancer Research Center, University of North Carolina at Chapel Hill, Wake Forest University Health Sciences, University of Massachusetts Memorial Health Care, University of Hawaii, University of Alabama at Birmingham, Indiana University Hospital/Melvin and Bren Simon Cancer Center, Cleveland Clinic Foundation, University of Chicago, Case Western Reserve University, Maine Medical Center – Scarborough Campus, Wichita CCOP, Abington Memorial Hospital, University of Colorado Cancer Center – Anschutz Cancer Pavilion, University of California Medical Center at Irvine-Orange Campus, MD Anderson Cancer Center, Women's Cancer Center of Nevada, University of Virginia, Mayo Clinic, The Hospital of Central Connecticut, Dana-Farber Cancer Institute, University of Southern California, Hartford Hospital, Delaware/Christiana Care CCOP, Virginia Commonwealth University, Iowa-Wide Oncology Research Coalition NCORP, Sanford NCI Community Oncology Research Program of the North Central Plains, Columbus NCI Community Oncology Research Program and Stony Brook University Medical Center.
Publisher Copyright:
© 2018 Elsevier Inc.
PY - 2019/3
Y1 - 2019/3
N2 - Introduction: Cabozantinib is a receptor tyrosine kinases inhibitor that targets MET (c-MET), VEGF receptor 2 (VEGFR2), RET, AXL, KIT, FLT-3, and TIE-2 and previously showed promising single agent activity in recurrent ovarian cancer. Methods: This was an open label, 1:1 randomized study of cabozantinib 60 mg orally (PO) daily versus weekly paclitaxel 80 mg/m 2 given 3 out of 4 weeks (NCT01716715); 111 patients were enrolled. Eligibility included persistent or recurrent epithelial ovarian, fallopian tube, or primary peritoneal carcinoma and at least one but no >3 prior chemotherapy regimens. Results: Median PFS was similar for both treatment groups and was 5.3 months for cabozantinib and 5.5 months for weekly paclitaxel (HR 1.11 (90% CI 0.77–1.61, p = 0.64)). Secondary analyses of overall survival (OS) and event free survival (EFS) showed that cabozantinib did not perform as well as weekly paclitaxel. Median OS for cabozantinib was 19.4 months and was not reached for weekly paclitaxel (HR 2.27 (90% CI 1.17–4.41, p = 0.04). EFS was also worse in the cabozantinib arm, 3.5 months, compared to weekly paclitaxel at 5.0 months (HR 1.81 (90% CI 1.24–2.63, p = 0.01). Overall response rate (ORR) was less for cabozantinib compared to weekly paclitaxel (7% versus 24.1%). Gastrointestinal toxicities, specifically nausea, diarrhea, and abdominal pain were worse in the cabozantinib arm. Conclusions: Median PFS was similar for cabozantinib and weekly paclitaxel. However, OS, EFS, and ORR were worse for cabozantinib compared to weekly paclitaxel. Cabozantinib given at this dose and schedule cannot be recommended as a treatment for recurrent ovarian cancer.
AB - Introduction: Cabozantinib is a receptor tyrosine kinases inhibitor that targets MET (c-MET), VEGF receptor 2 (VEGFR2), RET, AXL, KIT, FLT-3, and TIE-2 and previously showed promising single agent activity in recurrent ovarian cancer. Methods: This was an open label, 1:1 randomized study of cabozantinib 60 mg orally (PO) daily versus weekly paclitaxel 80 mg/m 2 given 3 out of 4 weeks (NCT01716715); 111 patients were enrolled. Eligibility included persistent or recurrent epithelial ovarian, fallopian tube, or primary peritoneal carcinoma and at least one but no >3 prior chemotherapy regimens. Results: Median PFS was similar for both treatment groups and was 5.3 months for cabozantinib and 5.5 months for weekly paclitaxel (HR 1.11 (90% CI 0.77–1.61, p = 0.64)). Secondary analyses of overall survival (OS) and event free survival (EFS) showed that cabozantinib did not perform as well as weekly paclitaxel. Median OS for cabozantinib was 19.4 months and was not reached for weekly paclitaxel (HR 2.27 (90% CI 1.17–4.41, p = 0.04). EFS was also worse in the cabozantinib arm, 3.5 months, compared to weekly paclitaxel at 5.0 months (HR 1.81 (90% CI 1.24–2.63, p = 0.01). Overall response rate (ORR) was less for cabozantinib compared to weekly paclitaxel (7% versus 24.1%). Gastrointestinal toxicities, specifically nausea, diarrhea, and abdominal pain were worse in the cabozantinib arm. Conclusions: Median PFS was similar for cabozantinib and weekly paclitaxel. However, OS, EFS, and ORR were worse for cabozantinib compared to weekly paclitaxel. Cabozantinib given at this dose and schedule cannot be recommended as a treatment for recurrent ovarian cancer.
KW - Anti-vascular
KW - Cabozantinib
KW - Ovarian cancer
KW - Paclitaxel
UR - http://www.scopus.com/inward/record.url?scp=85058794349&partnerID=8YFLogxK
U2 - 10.1016/j.ygyno.2018.12.008
DO - 10.1016/j.ygyno.2018.12.008
M3 - Article
C2 - 30587441
AN - SCOPUS:85058794349
SN - 0090-8258
VL - 152
SP - 548
EP - 553
JO - Gynecologic oncology
JF - Gynecologic oncology
IS - 3
ER -