Cabozantinib PFS Benefit in Frontline RCC Confirmed per Independent Review

Michael M. Morrissey, PhD

Results from a blinded, independent data review confirmed previous results from the CABOSUN trial showing that treatment with cabozantinib (Cabometyx) extended progression-free survival (PFS) compared with sunitinib (Sutent) for patients with previously untreated, intermediate- or poor-risk advanced renal cell carcinoma (RCC).

Results from the randomized, open-label phase II CABOSUN trial were first presented at the 2016 ESMO Congress and published in the Journal of Clinical Oncology. Cabozantinib reduced the risk of progression or death by 34% versus sunitinib as a first-line treatment for patients with metastatic RCC. The median PFS was 2.6 months longer with cabozantinib versus sunitinib, at 8.2 versus 5.6 months (HR, 0.66; 95% CI, 0.46-0.95; P = .012).

According to analysis by an independent radiology review committee, cabozantinib demonstrated a clinically meaningful and statistically significant reduction in the rate of disease progression or death as measured by PFS. Exelixis, manufacturer of cabozantinib, announced the findings in a press release.

“We are very pleased that CABOSUN’s primary endpoint of a statistically significant improvement of progression-free survival has been confirmed by the independent radiology review committee,” Michael M. Morrissey, PhD, Exelixis president and CEO, said in a release. “We continue in our focused efforts to complete the regulatory filing of cabozantinib for the treatment of patients with previously untreated advanced renal cell carcinoma and are on track to submit a supplemental new drug application in the third quarter of this year. Patients in the first-line setting with either intermediate- or poor-risk disease progress rapidly with sunitinib, a current standard of care, highlighting a clear need for new options that provide improved clinical benefit in this difficult-to-treat patient population.”

From July 2013 and April 2015, researchers randomly assigned patients to 60 mg daily cabozantinib (n = 79) or 50 mg daily sunitinib (n = 78) for 4 weeks on followed by 2 weeks off. Eligible patients were required to have locally advanced or metastatic clear-cell RCC, ECOG performance status 0 to 2, and had to be intermediate or poor risk per the IMDC criteria. Prior systemic treatment for RCC was not permitted.

Median age across the entire patient population was 63 years (range, 31-87), 78% of patients were male, and 92% 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%).

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). Cabozantinib was also superior for overall response rate (ORR), 46% versus 18%.

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%).

Patients in the cabozantinib arm were more likely to require dose reductions, 58% versus 49%. 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.