Exelixis has announced that the US Food and Drug Administration (FDA) approved Cabometyx (cabozantinib) tablets for the expanded indication of patients with advanced renal cell carcinoma (RCC). RCC is the most common form of kidney cancer in adults.

The FDA’s priority review and approval of Cabometyx was based on results from the randomized phase 2 CABOSUN trial in patients with previously untreated RCC, which demonstrated a statistically significant and clinically meaningful improvement in progression-free survival (PFS) 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.

 “Approval of Cabometyx is a true win for patients in the US with advanced renal cell carcinoma who now have a new first-line treatment option,” said Michael M. Morrissey, Ph.D., president and chief executive officer of Exelixis. “We are very pleased with the expanded indication and are prepared to bring Cabometyx to all eligible patients who may benefit from this important treatment option starting today. I would like to sincerely thank the patients and clinicians who participated in the CABOSUN trial, the Alliance and NCI-CTEP, as well as our dedicated clinical, medical and regulatory teams for their tireless efforts to this end. We would also like to acknowledge the review team at FDA for their expeditious review of our application.”

“The CABOSUN trial enrolled treatment-naïve patients with advanced kidney cancer, including those who are known to fare poorly, such as patients with intermediate- or poor-prognostic factors and those with bone metastases or multiple sites of metastatic disease,” said Toni Choueiri, M.D., director, Lank Center for Genitourinary Oncology, Dana-Farber Cancer Institute. “Physicians are already experienced in using Cabometyx in the second-line advanced RCC setting, and it is a much-needed advance to also now have Cabometyx as an option for their patients with previously untreated advanced RCC.”

The expanded approval of Cabometyx is based on results of the phase 2 CABOSUN trial, which met its primary endpoint of improving PFS. According to the independent radiology review committee analysis of the data, Cabometyx demonstrated a clinically meaningful and statistically significant 52 per cent 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 3 or 4 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 (PPE), 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.

“We at the Alliance for Clinical Trials in Oncology are very gratified that the CABOSUN study supported the approval of Cabometyx for the potential first-line treatment of all patients with advanced renal cell carcinoma. This trial exemplifies how NCI-sponsored studies can be efficient, accrue rapidly, and yield results highly relevant to the field,” said Michael J. Morris, M.D., medical oncologist at Memorial Sloan Kettering Cancer Center, and Chair of the Alliance Genitourinary (GU) Committee.

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 (NCI-CTEP) under the Cooperative Research and Development Agreement with Exelixis for the development of cabozantinib. These results were first presented by Dr. Toni Choueiri at the European Society for Medical Oncology (ESMO) 2016 Congress, and published in the Journal of Clinical Oncology (Choueiri, JCO, 2016). In June 2017, a blinded independent radiology review committee (IRC) 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 2 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.