A phase 2 randomised discontinuation trial of cabozantinib in patients with ovarian carcinoma

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).