Cabozantinib Versus Sunitinib As Initial Targeted Therapy for Patients With Metastatic Renal Cell Carcinoma of Poor or Intermediate Risk: The Alliance A031203 CABOSUN Trial

Abstract

Purpose Cabozantinib is an oral potent inhibitor of vascular endothelial growth factor receptor 2, MET, and AXL and is a standard second-line therapy for metastatic renal cell carcinoma (mRCC). This randomized phase II multicenter trial evaluated cabozantinib compared with sunitinib as first-line therapy in patients with mRCC. Patients and Methods Eligible patients had untreated clear cell mRCC and Eastern Cooperative Oncology Group performance status of 0 to 2 and were intermediate or poor risk per International Metastatic Renal Cell Carcinoma Database Consortium criteria. Patients were randomly assigned at a one-to-one ratio to cabozantinib (60 mg once per day) or sunitinib (50 mg once per day; 4 weeks on, 2 weeks off). Progression-free survival (PFS) was the primary end point. Objective response rate (ORR), overall survival, and safety were secondary end points. Results From July 2013 to April 2015, 157 patients were randomly assigned (cabozantinib, n = 79; sunitinib, n = 78). Compared with sunitinib, cabozantinib treatment significantly increased median PFS (8.2 v 5.6 months) and was associated with a 34% reduction in rate of progression or death (adjusted hazard ratio, 0.66; 95% CI, 0.46 to 0.95; one-sided P = .012). ORR was 33% (95% CI, 23 to 44) for cabozantinib versus 12% (95% CI, 5.4 to 21) for sunitinib. All-causality grade 3 or 4 adverse events were 67% for cabozantinib and 68% for sunitinib and included diarrhea (cabozantinib, 10% v sunitinib, 11%), fatigue (6% v 15%), hypertension (28% v 22%), palmar-plantar erythrodysesthesia (8% v 4%), and hematologic adverse events (3% v 22%). Conclusion Cabozantinib demonstrated a significant clinical benefit in PFS and ORR over standard-of-care sunitinib as first-line therapy in patients with intermediate- or poor-risk mRCC.

Fig 1.

Flowchart of patient disposition through April 11, 2016.

Fig 2.

Kaplan-Meier plot of progression-free survival through April 11, 2016. Disease progression was assessed per investigator. All randomly assigned patients were included in the analysis.

Fig 3.

Best target lesion change from baseline with (A) cabozantinib and (B) sunitinib. Data are as of April 11, 2016. (A) Three patients in the cabozantinib group and (B) 16 patients in the sunitinib group were not evaluable because they had no postbaseline imaging assessments (Table 2).

Fig 4.

Kaplan-Meier plot of overall survival as of September 15, 2016.

Fig A1.

Forest plots of progression-free survival through April 11, 2016. All randomly assigned patients were included in the analyses. Hazard ratios (HRs) are unadjusted with the exception of that for the overall population, where stratification factors for random assignment were used. IMDC, International Metastatic Renal Cell Carcinoma Database Consortium; PFS, progression-free survival.