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ESMO 2017

ESMO 2017: Progression-free survival by independent review and updated overall survival results from Alliance A031203 trial (CABOSUN): cabozantinib versus sunitinib as initial targeted therapy for patients with metastatic renal cell carcinoma

Madrid, Spain (UroToday.com) Dr. Choueiri and colleagues presented updated results from the CABOSUN trial, which randomized cabozantinib versus sunitinib as initial targeted therapy for patients with metastatic renal cell carcinoma (mRCC). Cabozantinib, an oral, potent inhibitor of MET, AXL, and VEGFR2, improved investigator-assessed PFS (primary endpoint) compared with sunitinib as initial targeted therapy in patients with mRCC of poor or intermediate risk [1]. The median PFS per investigator review was 8.2 months for cabozantinib compared to 5.6 months (HR 0.66, 95%CI 0.46-0.95) for sunitinib. The purpose of the current study was to update these results, as well as provide overall survival (OS) outcomes with a data cutoff of July 1, 2017.

Key inclusion criteria for this trial included (i) patients with untreated clear-cell mRCC, (ii) ECOG performance status 0-2, and (iii) poor or intermediate risk disease per the International mRCC Database Consortium (IMDC) criteria [2]. There were 157 patients randomized 1:1 to receive cabozantinib 60 mg QD (n=79) or sunitinib 50 mg QD (n=78), 4 weeks on/2 weeks off, stratified by IMDC risk group and the presence of bone metastases (yes vs no). PFS analyses were reported per a blinded independent radiology committee and subset analyses were by stratification factors and MET expression based on immunohistochemistry. Radiographic images for 156 of 157 enrolled patients were available for assessment by the independent radiology committee. PFS was significantly increased for cabozantinib compared with sunitinib (median 8.6 vs 5.3 months; HR 0.48, 95%CI 0.31 to 0.74), which were improved compared to the initial data reported (HR 0.48 vs 0.66). Subgroup analyses of PFS based on the stratification factors and tumor MET levels were consistent with results for the overall population. Updated OS analysis with a median follow-up of 30.8 months and a total of 90 deaths showed a median OS of 26.6 months for cabozantinib vs 21.2 months for sunitinib (HR 0.79, 95%CI 0.53-1.2). Safety profiles were consistent with those previously reported. The incidence of all-causality grade 3 or 4 adverse events was 68% with cabozantinib and 65% with sunitinib. Discontinuations due to adverse events occurred for 16 patients in each treatment arm.

The authors concluded that cabozantinib significantly increased PFS per independent review committee compared with sunitinib as initial targeted therapy in patients with mRCC. Cabozantinib resulted in improved OS compared to sunitinib, although these results were not statistically significant.

Speaker: Toni K. Choueiri, Dana Farber Cancer Center, Boston, United States of America

Co-Authors: C. Hessel (South San Francisco, United States of America) S. Halabi (Durham, United States of America) B. Sanford (Durham, United States of America) O. Hahn (Chicago, United States of America) M. D. Michaelson (Boston, United States of America) M. Walsh (Boston, United States of America) T. Olencki (Columbus, United States of America) J. Picus (St Louis, United States of America) E. J. Small (San Francisco, United States of America) S. Dakhil (Wichita, United States of America) C. Scheffold (South San Francisco, United States of America) D. J. George (Durham, United States of America) M. J. Morris (New York, 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

References:

1. Choueiri TK, Halabi S, Sanford BL, et al. Cabozantinib versus Sunitinib as initial targeted therapy for patients with metastatic renal cell carcinoma of poor or intermediate risk: The Alliance A031203 CABOSUN Trial. J Clin Oncol 2017;35(6):591-597.
2. Heng DY, Xie W, Regan MM, et al. Prognostic factors for overall survival in patients with metastatic renal cell carcinoma treated with vascular endothelial growth factor-targeted agents: Results from a large, multicenter study. J Clin Oncol 2009;27(34):5749-5799.