FDA approved Cabometyx (cabozantinib) tablets for the expanded indication of patients with advanced renal cell carcinoma.
FDA’s priority review and approval of Cabometyx was based on results from the randomized phase II CABOSUN trial in patients with previously untreated RCC, which demonstrated a statistically significant and clinically meaningful improvement in progression-free survival versus sunitinib, a current standard of care.
The label expansion follows the initial FDA approval of Cabometyx in April 2016 for the treatment of patients with advanced RCC who have previously received anti-angiogenic therapy.
The expanded approval of Cabometyx is based on results of the phase II CABOSUN trial, which met its primary endpoint of improving PFS. According to the independent radiology review committee analysis of the data, Cabometyx, sponsored by Exelixis Inc., demonstrated a clinically meaningful and statistically significant 52 percent reduction in the rate of disease progression or death (HR 0.48, 95% CI 0.31-0.74, two-sided P=0.0008). Median PFS for Cabometyx was 8.6 months versus 5.3 months for sunitinib, corresponding to a 3.3 month (62 percent) improvement.
All causality grade III or IV adverse reactions occurred in 68 percent of patients receiving Cabometyx and 65 percent of patients receiving sunitinib.
The most frequent all causality Grade 3-4 adverse reactions (≥5 percent) in patients treated with Cabometyx were hypertension, diarrhea, hyponatremia, hypophosphatemia, palmar-plantar erythrodysesthesia, fatigue, increased ALT, decreased appetite, stomatitis, pain, hypotension, and syncope. Twenty-one percent of patients in the Cabometyx arm compared to 22 percent of patients receiving sunitinib discontinued treatment due to adverse events.
On May 23, 2016, Exelixis announced that CABOSUN met its primary endpoint, demonstrating a statistically significant and clinically meaningful improvement in PFS compared with sunitinib in patients with advanced intermediate- or poor-risk RCC as determined by investigator assessment.
The CABOSUN study was conducted by The Alliance for Clinical Trials in Oncology and was sponsored by the National Cancer Institute-Cancer Therapy Evaluation Program under the Cooperative Research and Development Agreement withExelixis for the development of cabozantinib.
These results were first presented by Toni Choueiri at the European Society for Medical Oncology 2016 Congress, and published in the Journal of Clinical Oncology (Choueiri, JCO, 2016).
In June 2017, a blinded independent radiology review committee confirmed that cabozantinib provided a clinically meaningful and statistically significant improvement in the primary efficacy endpoint of investigator-assessed PFS. Results from the IRC review were presented by Dr. Toni Choueiri at the ESMO 2017 Congress.
CABOSUN was a randomized, open-label, active-controlled phase II trial that enrolled 157 patients with advanced RCC determined to be intermediate- or poor-risk by the IMDC criteria. Patients were randomized 1:1 to receive cabozantinib (60 mg once daily) or sunitinib (50 mg once daily, 4 weeks on followed by 2 weeks off).
The primary endpoint was PFS. Secondary endpoints included overall survival, objective response rate and safety. Eligible patients were required to have locally advanced or metastatic clear-cell RCC, ECOG performance status 0-2 and had to be intermediate or poor risk per the IMDC criteria (Heng, JCO, 2009). Prior systemic treatment for RCC was not permitted.
