CABOSUN Results Confirm Improved PFS With Cabozantinib for Advanced RCC

Cabozantinib reduced the risk for disease progression or death by 52% compared with sunitinib in patients with previously untreated advanced renal cell carcinoma (RCC), according to updated results from the CABOSUN trial (LBA38_PD) presented at the 2017 European Society for Medical Oncology (ESMO) Congress in Madrid.

These updated data were from the blinded independent radiology review committee (IRC) and were presented by Toni K. Choueiri, MD, director of the Lank Center for Genitourinary Oncology at the Dana-Farber Cancer Institute in Boston. These data confirmed previous data from the investigator-assessed progression-free survival (PFS) analysis.

The trial included patients with intermediate or poor prognostic factors who had a number of other independent adverse prognostic factors such as bone metastases.

“These updated analyses from CABOSUN consistently show that cabozantinib provided a statistically significant decrease in the rate of disease progression or death compared to sunitinib, a current standard of care-potentially offering a new treatment option for physicians to treat patients in the first-line advanced RCC setting,” said Choueiri.

The trial included 157 patients with advanced disease determined to be intermediate or poor risk and randomly assigned them to cabozantinib 60 mg once daily or sunitinib 50 mg once daily for 4 weeks on, then 2 weeks off. The primary endpoint was PFS.

The median PFS was 8.6 months for cabozantinib compared with 5.3 months for sunitinib, a 3.3-month improvement. The IRC analysis showed a 52% reduction in the rate of disease progression or death (hazard ratio [HR], 0.48; 95% CI, 0.31–0.74). In the previously published investigator-assessed analysis, cabozantinib showed a 44% reduction in the risk for disease progression or death (HR, 0.66; 95% CI, 0.46–0.95).

Choueiri also presented updated overall survival data. This showed a favorable trend for patients randomized to cabozantinib compared with sunitinib, but the difference was not statistically significant. The median overall survival was 26.6 months for cabozantinib compared with 21.2 months for sunitinib (HR, 0.80; 95% CI, 0.53–1.21).

The most common all-causality grade 3 /4 adverse events in more than 5% of patients for cabozantinib (n = 78) and sunitinib (n = 72), respectively, were diarrhea (10% vs 11%), hypertension (28% vs 21%), fatigue (6% vs 17%), increased alanine aminotransferase (ALT; 5% vs 0%), decreased appetite (5% vs 1%), palmar-plantar erythrodysesthesia syndrome (8% vs 4%), decreased platelet count (1% vs 11%), and stomatitis (5% vs 6%). Twenty-one percent of patients in the cabozantinib arm and 22% of patients in the sunitinib arm discontinued treatment due to adverse events.

“This patient population fares poorly and is in need of new therapies to better control their disease,” Choueiri said in a press release.

Cabozantinib’s manufacturer, Exelixis, has filed a supplemental New Drug Application based on CABOSUN with the US Food and Drug Administration for approval in previously untreated advanced RCC.