Faculty Collaboration Database

Phase II randomised discontinuation trial of cabozantinib in patients with advanced solid tumours. Eur J Cancer 2017 Nov;86:296-304

Date

10/24/2017

Pubmed ID

29059635

DOI

10.1016/j.ejca.2017.09.011

Scopus ID

2-s2.0-85031818140 (requires institutional sign-in at Scopus site)   59 Citations

Abstract

BACKGROUND: Cabozantinib is an inhibitor of tyrosine kinases, including MET, vascular endothelial growth factor receptor, AXL and RET. This multi-cohort phase II randomised discontinuation trial explored anticancer activity of cabozantinib in nine tumour types.

PATIENTS AND METHODS: Cabozantinib was administered (100 mg, once daily) to patients with advanced, recurrent or metastatic cancers. Those with stable disease at week 12 were randomised 1:1 to cabozantinib or placebo. Primary end-points were objective response rate (ORR) at week 12 and progression-free survival (PFS) in the randomised phase.

RESULTS: A total of 526 patients were enrolled. The highest ORR was observed in ovarian cancer (OC) (21.7%); the largest PFS benefit was observed in castration-resistant prostate cancer (CRPC) (median 5.5 versus 1.4 months for placebo; hazard ratio 0.14, 95% confidence interval: 0.04, 0.52). Disease control rates were >40% for CRPC, OC, melanoma, metastatic breast cancer (MBC), hepatocellular carcinoma (HCC) and non-small cell lung cancer. Median duration of response ranged from 3.3 (MBC) to 11.2 months (OC). Encouraging efficacy results and symptomatic improvements prompted early suspension of the randomised stage and conversion to open-label non-randomised expansion cohorts. Dose reductions to manage adverse events (AEs) occurred in 48.7% of patients. The most frequent grade III-IV AEs were fatigue (12.4%), diarrhoea (10.5%), hypertension (10.5%) and palmar-plantar erythrodysesthesia syndrome (8.7%).

CONCLUSIONS: Clinical antitumour activity of cabozantinib was observed in a subset of tumour types: CRPC and OC were evaluated further in expansion cohorts. Phase III programs were initiated in CRPC and HCC. Interpretation of efficacy outcomes was limited by early termination of the randomised portion of the trial.

TRIAL REGISTRATION NUMBER: NCT00940225.

Author List

Schöffski P, Gordon M, Smith DC, Kurzrock R, Daud A, Vogelzang NJ, Lee Y, Scheffold C, Shapiro GI

Author

Razelle Kurzrock MD Center Associate Director, Professor in the Medicine department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Anilides
Antineoplastic Agents
Belgium
Disease Progression
Disease-Free Survival
Drug Administration Schedule
Early Termination of Clinical Trials
Female
Humans
Israel
Kaplan-Meier Estimate
Male
Neoplasms
Protein Kinase Inhibitors
Pyridines
Taiwan
Time Factors
Treatment Outcome
United States