Cabozantinib (Cabo), an oral, potent inhibitor of MET, AXL, and VEGFR2, improved investigator-assessed PFS (primary endpoint) compared with sunitinib (Sun) as initial targeted therapy in pts with mRCC of poor or intermediate risk (Choueiri, JCO 2016). Median PFS per investigator was 8.2 months (mo) vs 5.6 mo (HR 0.66, 95% CI 0.46 to 0.95; one-sided p = 0.012) for Cabo vs Sun.
Eligible pts had untreated clear-cell mRCC, ECOG performance status 0-2, and poor or intermediate risk disease per the International mRCC Database Consortium (IMDC) criteria (Heng, JCO 2009). 157 pts were randomized 1:1 to receive Cabo (60 mg QD) or Sun (50 mg QD, 4 weeks on/2 weeks off), stratified by IMDC risk group and the presence of bone metastases (yes vs no). We present PFS analyses per blinded independent radiology committee (IRC), subset analyses by stratification factors and MET expression based on immunohistochemistry (IHC), and an update of OS with a data cutoff of July 1, 2017.
Radiographic images for 156 of 157 enrolled pts were available for assessment by the IRC. PFS per IRC was significantly increased for Cabo compared with Sun (median of 8.6 vs 5.3 mo; HR 0.48, 95% CI 0.31 to 0.74; two-sided p = 0.0008). Subgroup analyses of PFS per IRC 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 mo and a total of 90 deaths showed a median OS of 26.6 mo for Cabo vs 21.2 mo for Sun (HR 0.79, 95% CI 0.53 to 1.2; two-sided p = 0.27). Safety profiles were consistent with those previously reported. The incidence of all-causality grade 3 or 4 AEs was 68% with Cabo and 65% with Sun. Discontinuations due to AEs occurred for 16 pts in each treatment arm.
Cabo significantly increased PFS per IRC compared with Sun as initial targeted therapy in pts with mRCC. Subgroup analyses were consistent with the overall population results. Previously reported results for PFS per investigator were consistent with results reported here.
Clinical trial identification
Legal entity responsible for the study
Alliance for Clinical Trials in Oncology
NCI, CTEP, Alliance
T.K. Choueiri: Consulting/Advisory: Pfizer, Bayer, Novartis, Merck, BMS, Genentech, Eisai, Prometheus, Cerulean, AstraZeneca, Peloton, Exelixis; Research Funding (Inst): Pfizer, Novartis, Merck, Exelixis, Tracon, BMS, AstraZeneca, Peloton, Genentech, Celldex, Takeda. C. Hessel, C. Scheffold: Employment/Stock Ownership: Exelixis. S. Halabi: Consulting/Advisory: Bayer, Genentech. O. Hahn: Honoraria: Cardinal Health (relative), Via Oncology; Advisory: Pfizer. M.D. Michaelson: Employment: Jounce Therapeutics (relative); Consulting/Advisory: Novartis, Medivation, Pfizer, Exelixis, Eisai; Research Funding (Inst): Pfizer, Eisai, Argos Therapeutics, Millennium, Novartis, Tracon. T. Olencki: Research Funding (Inst): BMS, Pfizer, Tracon. J. Picus: Consulting/Advisory: Novo Nordisk; Research Funding: Novartis, Bioclin, Altor BioScience, Agensys, Oncogenex, Mirati Therapeutics, Astex. E.J. Small: Stock Ownership: Fortis Therapeutics, Harpoon Therapeutics; Consulting/Advisory: Gilead, Dendreon. D.J. George: Consulting/Advisory/Research Funding: Exelixis, Novartis, Pfizer, GSK, Astellas, Innocrin, Genentech, BMS; Consulting/Advisory: Bayer, Dendreon, Medivation, BIND, Sanofi, Progenics, Clovis, Merck; Research Funding: Janssen, Progenics, Astellas, Millennium M.J. Morris: Consulting/Advisory: Bayer, Millennium Pharmaceuticals, Progenics: Research Funding (Inst): Bayer, Sanofi, Janssen, Endocyte All other authors have declared no conflicts of interest.