cabozantinib and Fallopian-Tube-Neoplasms

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.. This was an open label, 1:1 randomized study of cabozantinib 60 mg orally (PO) daily versus weekly paclitaxel 80 mg/m. 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.. 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.

Topics: Administration, Oral; Adult; Aged; Aged, 80 and over; Anilides; Antineoplastic Agents, Phytogenic; Carcinoma, Ovarian Epithelial; Drug Administration Schedule; Fallopian Tube Neoplasms; Female; Humans; Middle Aged; Neoplasm Recurrence, Local; Ovarian Neoplasms; Paclitaxel; Peritoneal Neoplasms; Protein Kinase Inhibitors; Pyridines

To evaluate the efficacy and tolerability of cabozantinib in recurrent clear cell ovarian, primary peritoneal or fallopian tube cancer.. Patients with recurrent ovarian, fallopian or primary peritoneal tumors with at least 50% clear cell histomorphology, measurable disease, one or two prior regimens and ECOG performance status 0-2 received cabozantinib 60 mg orally once daily continuously, in 4-week cycles until disease progression or unacceptable toxicity. Primary endpoints were progression-free survival (PFS) at six months and complete or partial tumor response (as assessed by RECIST 1.1). Secondary endpoints included toxicity, PFS, and overall survival (OS).. Over 19 months, 13 patients were accrued. Fifty-four percent of patients were ≥60 years of age. Performance statuses of 0 and 1 comprised 8 and 5 patients. No objective tumor responses were seen. Three (23% [95% CI: 5%, 54%]) of 13 patients had PFS ≥6 months, including one patient who received cabozantinib for 23 cycles and was still on treatment as of the data cut-off date. Median PFS and OS were 3.6 and 8.1 months, respectively. There was one patient with a grade 5 event: a thromboembolic event considered possibly related to study therapy; patient's cause of death was determined to be due to disease and protocol treatment. Four other patients had thromboembolic events (two grade 3 and one each grade 1 and grade 2). Other grade 3 or higher events reported in two or more patients were nausea, vomiting, fatigue, dyspnea, and dehydration.. Cabozantinib demonstrated minimal activity in the second- and third-line treatments of clear cell ovarian, fallopian tube or primary peritoneal carcinoma.

Topics: Adenocarcinoma, Clear Cell; Adult; Aged; Anilides; Fallopian Tube Neoplasms; Female; Humans; Middle Aged; Ovarian Neoplasms; Peritoneal Neoplasms; Pyridines