Toni K. Choueiri, MD
Cabozantinib (Cabometyx) reduced the risk of progression or death by 34% versus sunitinib (Sutent) as a first-line treatment for patients with metastatic renal cell carcinoma (RCC), according to results from the phase II CABOSUN trial published in the Journal of Clinical Oncology
The median progression-free survival (PFS) was 2.6 months higher with cabozantinib versus sunitinib. The overall response rate (ORR) was 46% versus 18%, respectively.
“In this smaller trial, cabozantinib was able to improve outcomes compared with sunitinib. The results showed that the primary endpoint, which was progression-free survival, was prolonged with cabozantinib over sunitinib,” lead investigator Toni K. Choueiri, MD, clinical director, Lank Center for Genitourinary Oncology, director, Kidney Cancer Center, senior physician, Dana-Farber Cancer Institute, said in an interview with OncLive
“The results were not just statistically significant but also clinical relevant and corresponded to a decrease in the hazard of progression or death of over 30%,” Choueiri added. “This has the potential to change the standard of care and how we treat frontline advanced RCC.”
Between July 2013 and April 2015, the open-label, randomized phase II CABOSUN trial enrolled 157 patients with intermediate- or poor-risk locally advanced or metastatic clear-cell RCC. The Alliance for Clinical Trials in Oncology conducted the trial under a collaboration between Exelixis and the NCI’s Cancer Therapy Evaluation Program.
Patient characteristics were well balanced between the treatment arms. The median age across the entire patient population was 63 years (range, 31-87), 78% of patients were male, and 92% of patients were white. Thirty-six percent of patients had bone metastases and 75% of patients had prior nephrectomy. Patients had an ECOG performance status of 0 (45.9%), 1 (41.4%), or 2 (12.7%).
Patients were randomized in a 1:1 ratio to 60 mg once daily of cabozantinib (n = 79) or 50 mg once daily (4 weeks on, 2 weeks off) of sunitinib (n = 78). The primary outcome measure was PFS, with secondary endpoints including overall survival (OS) and ORR.
The median PFS was 8.2 months (95% CI, 6.2-8.8) in the cabozantinib group compared with 5.6 months (95% CI, 3.4-8.1) in the sunitinib cohort (HR, 0.66; 95% CI, 0.46-0.95; P
The median OS was 30.3 months in the cabozantinib arm versus 21.8 months in the sunitinib arm (HR, 0.80; 95% CI 0.50-1.26).
In 87% of the cabozantinib arm, there was some reduction in target lesions, compared with 44% of the sunitinib cohort. The stable and progressive disease rates were 33% versus 36% and 18% versus 26%, respectively.
Adverse events (AEs) of any grade occurred in approximately 99% of each arm. The most common all-grade AEs with cabozantinib versus sunitinib included fatigue (85.9% vs 81.9%), hypertension (80.8% vs 68.1%), diarrhea (71.8% vs 52.8%), increased AST (61.5% vs 31.9%), and increased ALT (55.1% vs 27.8%).
Grade ≥3 AEs occurred in 66.7% of the cabozantinib arm versus 68.1% of the sunitinib arm. Common grade ≥3 AEs included diarrhea (10.3% with cabozantinib vs 11.1% with sunitinib), fatigue (6% vs 15%), hypertension (28.2% vs 22.2%), palmar-plantar erythrodysesthesia (7.7% vs 4.2%) and fatigue (6.4% vs 15.3%).
Dose reductions occurred in 58% and 49% of the cabozantinib and sunitinib arms, respectively. There were 16 AE-related discontinuations in each arm.
Cabozantinib is approved in the United States and Europe as a treatment for patients with advanced RCC who have received prior antiangiogenic therapy.
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 [published online November 14, 2016]. J Clin Oncol. doi:10.1200/JCO.2016.70.7398