ASCO GU 2018: Title Dose Escalation of Cabozantinib as a Viable Option for the Treatment of mRCC

San Francisco, CA ( 
Cabozantinib (C) is a tyrosin kinase inhibitor (TKI) specific for VEGFR, MET and AXL. The phase-3 registration trial METEOR showed that C significantly improved progression-free and overall survival compared to Everolimus in patients with advanced/metastatic renal cell carcinoma (RCC) after failure of at least one VEGFR TKI.1 In METEOR, starting dose for C was 60 mg once daily and dose de-escalation to 40 or 20 mg or stopping of C was done based on toxicity. The median dose was 43 mg, and the dose had to be reduced in 62% of patients. The recommended starting dose of C is 60 mg. The authors hypothesized that starting with 40 mg of C and escalating to 60 mg after getting accustomed to side effects may lead to a higher median dose of C.

This is a report on 20 RCC patients all started with C 40 mg and escalated to 60 mg when possible. The authors calculated the median time on therapy and the median dose and determined the best response.

The median time on C was 77 days for the patients having stopped therapy (n = 9). The median dose of C for the whole cohort was 46.0 mg. For the patients still on therapy (n = 11), the median dose was 47.7 mg. Eleven (55%) patients could be escalated to 60 mg (10 (91%) remained on 60 mg) and only 5 (25%) of patients had to be de-escalated to 20 mg. C did not have to be stopped due to toxicity. For best response, 47% reached partial remission, 13%  were stable and 40% experienced progressive disease.

Starting with 40 mg of C and escalating to 60 mg when possible may lead to a higher median dose of C compared to standard vice versa and seems to achieve responses comparable with the METEOR trial.1 These findings are limited by the small number of patients but warrant a prospective trial directly comparing both the escalating and de-escalating dosing schemes.

Presented by: Martin Boegemann, Muenster, Germany

Written by: Hanan Goldberg, MD, Urologic Oncology Fellow (SUO), University of Toronto, Princess Margaret Cancer Centre @GoldbergHanan, at the 2018 American Society of Clinical Oncology Genitourinary (ASCO GU) Cancers Symposium, February 8-10, 2018 - San Francisco, CA

1.Choueiri TK, Escudier B, Powles T, et al. Cabozantinib versus Everolimus in Advanced Renal-Cell Carcinoma. New England Journal of Medicine 2015; 373(19): 1814-23.