Cabozantinib (C) prolongs overall survival (OS) and progression-free survival (PFS) in patients with metastatic clear-cell renal cell carcinoma (ccRCC) that progressed on first-line VEGFR-TKI. No standard of care systemic therapy exists for the management of patients with metastatic vhRCC.
This is a retrospective, IRB approved study of patients with vhRCC who received cabozantinib at MD Anderson Cancer Center from January 2014-January 2017. 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. Descriptive statistics, the Kaplan Meier method and the log rank test were applied using Microsoft Excel and GraphPad Prism version 6 software.
|N = 30|
|Gender||Male = 26 (86.7%)|
|Age, median (range)||58.4 years (25-81)|
|Prior Nephrectomy||27 (90%)|
|Histology||Papillary (P) 17 Chromophobe (Chr) 6 Other: unclassified 3, translocation 2, sarcomatoid (sarc) 1, mucinous tubular/spindle cell 1|
|Prognostic Risk Group MSKCC IMDC||Good/Intermediate/Poor 2/20/8 2/23/5|
|Number of Prior Therapies 0 1 >1 Median (range) Previous VEGFR Tyrosine Kinase Inhibitor||3 7 20 2 (0-5) 26|
Median PFS was 8.6 months (mos) (95%CI: 6.1-14.7), and median OS was 22.7 mos (95%CI:10.8-NR), 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 PRs (2 P, 1 Chr, 1 unclassifed) for a 14% ORR. For the entire cohort, 20 of 30 (66.7%) with stable disease, and 6 of 30 with progressive disease (20%), for a disease control rate of 24 of 30 (80%). Of 21 patients who started C at 60 mg/d, 12 (57%) required dose reduction due to toxicity. Multiple patients required treatment breaks but none discontinued therapy due to toxicity.
In this retrospective study, C produced a clinically meaningful benefit in patients with metastatic vhRCC, the majority of whom had PD on prior VEGFR-TKIs. Prospective trials of C in vhRCC are warranted and planned.
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Legal entity responsible for the study
Matthew T Campbell
M.T. Campbell: Serve on advisory boards for Eisai and AstraZeneca. M.A. Bilen: Advisory board for Exelixis. N. Tannir: Served as a consultant and has served on advisory board for Exelixis. All other authors have declared no conflicts of interest.