Schöffski P, et al. - Researchers performed this multi-cohort phase II randomised discontinuation trial to determine anticancer activity of cabozantinib in nine tumour types. In this study, cabozantinib demonstrated antitumour activity in multiple solid-tumour types. Results supported initiation of phase III programs in castration-resistant prostate cancer and hepatocellular carcinoma.

Methods

• Patients with advanced, recurrent or metastatic cancers received cabozantinib (100 mg, once daily).
• Researchers randomized 1:1 patients with stable disease at week 12 to cabozantinib or placebo.
• For this study, objective response rate (ORR) at week 12 and progression-free survival (PFS) in the randomised phase were the primary end-points.

Results

• Researchers enrolled 526 patients.
• In ovarian cancer (OC), findings revealed the highest ORR (21.7%).
• In castration-resistant prostate cancer (CRPC), findings revealed the largest PFS benefit (median 5.5 vs 1.4 months for placebo; hazard ratio 0.14, 95% confidence interval: 0.04, 0.52).
• For CRPC, OC, melanoma, metastatic breast cancer (MBC), hepatocellular carcinoma (HCC) and non–small cell lung cancer, they observed disease control rates of >40%.
• In this study, median duration of response ranged from 3.3 (MBC) to 11.2 months (OC).
• They achieved encouraging efficacy results and symptomatic improvements which prompted early suspension of the randomised stage and conversion to open-label non-randomised expansion cohorts.
• To manage adverse events (AEs), they performed dose reductions in 48.7% of patients.
• As per observations, the most common grade III–IV AEs included fatigue (12.4%), diarrhoea (10.5%), hypertension (10.5%) and palmar-plantar erythrodysesthesia syndrome (8.7%).