Between January 2014 and January 2017, 30 patients with variant histology RCC (papillary type I/II/NOS, chromophobe, translocation, mucinous tubular/spindle cell, sarcomatoid, and unclassified) received cabozantinib. Information collected from the medical records included the baseline characteristics, toxicity, dose reductions, and OS. A blinded radiologist assessed the radiographic response using RECIST v1.1.
The most common histology was papillary (57%), followed by chromophobe (20%), and unclassified (10%). The median age was 58 years (range 25-81), most patients were male (87%), the majority had previously undergone a radical nephrectomy (90%), and the majority had previously received a TKI (87%). 78% of patients were IMDC intermediate risk and 17% were poor risk. Median PFS was 8.6 months (95%CI: 6.1-14.7), and median OS was 22.7 months (95%CI:10.8-NR), over a median follow up 10.6 months (95%CI: 7.1-14.1). There were no significant differences detected between patients with papillary versus non-papillary histologies with respect to PFS or OS. At last follow up, 13 patients remain on treatment with median time on therapy for all patients of 15.0 months. Of the 28 patients with measurable disease, there were 4 confirmed partial responses (2 papillary, 1 chromophobe, 1 unclassified) for a 14% objective response rate. For the entire cohort, 20 of 30 (66.7%) patients had stable disease, and 6 of 30 (20%) had progressive disease, for a disease control rate of 24 of 30 (80%). Of 21 patients who started cabozantinib at 60 mg/d, 12 (57%) required dose reduction due to toxicity. Multiple patients required treatment breaks but none discontinued therapy due to toxicity.
The authors concluded that in this retrospective study, cabozantinib produced a clinically meaningful benefit in patients with metastatic variant histology RCC, the majority of whom had progressive disease on prior VEGFR-TKIs. Ultimately, prospective trials of cabozantinib in variant histology RCC are warranted and planned.
Speaker: Matthew T. Campbell, The University of Texas, MD Anderson Cancer Center, Houston, United States of America
Co-Authors: M. A. Bilen (Atlanta, United States of America) C. Duran (Houston, United States of America) E. Altinmakas (Houston, United States of America) Z. Lim (Houston, United States of America) A. Shah (Houston, United States of America) E. Jonasch (Houston, United States of America) N. Tannir (Houston, United States of America)
Written By: Zachary Klaassen, MD, Urologic Oncology Fellow, University of Toronto, Princess Margaret Cancer Centre, Twitter: @zklaassen_md at the European Society for Medical Oncology Annual Congress - September 8 - 12, 2017 - Madrid, Spain
Choueiri TK, Escudier B, Powles T, et al. Cabozantinib versus Everolimus in Advanced Renal-Cell Carcinoma. N Engl J Med 2015;373(19):1814-1823.