Title | A phase 2 randomised discontinuation trial of cabozantinib in patients with ovarian carcinoma. |
Publication Type | Journal Article |
Year of Publication | 2017 |
Authors | Vergote IB, Smith DC, Berger R, Kurzrock R, Vogelzang NJ, Sella A, Wheler J, Lee Y, Foster PG, Weitzman R, Buckanovich RJ |
Journal | Eur J Cancer |
Volume | 83 |
Pagination | 229-236 |
Date Published | 2017 09 |
ISSN | 1879-0852 |
Keywords | Adult, Aged, Anilides, Antineoplastic Agents, Carcinoma, Female, Humans, Middle Aged, Ovarian Neoplasms, Protein Kinase Inhibitors, Pyridines, Survival Analysis |
Abstract | BACKGROUND: Cabozantinib (XL184), an orally bioavailable inhibitor of vascular endothelial growth factor receptor 2 and MET, was assessed in a cohort of ovarian carcinoma patients as part of a phase 2 randomised discontinuation trial (RDT) with cohorts from nine different tumour types. PATIENTS AND METHODS: Patients received 100-mg cabozantinib daily. Those with stable disease (SD) per Response Evaluation Criteria in Solid Tumors at week 12 were randomised to cabozantinib or placebo. Primary end-points were objective response rate (ORR) at week 12 and progression-free survival (PFS) after random assignment. RESULTS: Seventy patients with ovarian carcinoma, 50% of whom were platinum refractory/resistant, were enrolled in this RDT. Median PFS from day 1 was 5.5 months for all patients. The ORR at week 12 was 21%; one patient achieved a complete response (CR), and 14 patients (20%) achieved a confirmed partial response (PR). The overall disease control rate (CR + PR + SD) at week 12 was 50%. Throughout the study, 70% of the patients with ≥1 postbaseline scan had tumour regression, and randomisation was discontinued early. For patients with SD randomised to cabozantinib, PFS was 5.9 months after randomisation. The most common grade 3/4 adverse events were diarrhoea (14%), palmar-plantar erythrodysesthesia syndrome (6%), asthenia (6%), hypertension (6%) and neutropenia (6%). Dose reductions were required in 37% of the patients during the first 12 weeks. CONCLUSION: Cabozantinib demonstrates clinical activity, with acceptable toxicities, in patients with ovarian carcinoma based on ORR and regression of tumour target lesions. REGISTRATION: This trial is registered at ClinicalTrial.gov (NCT00940225). |
DOI | 10.1016/j.ejca.2017.06.018 |
Alternate Journal | Eur. J. Cancer |
PubMed ID | 28755607 |
Submitted by kej2006 on June 6, 2018 - 4:12pm