Cabozantinib Submitted for FDA Approval in Frontline RCC


Exelixis has submitted a supplemental New Drug Application to the FDA for the multikinase inhibitor cabozantinib as treatment for previously untreated patients with advanced renal cell carcinoma.

Michael M. Morrissey, PhD

Michael M. Morrissey, PhD

Exelixis has submitted a supplemental New Drug Application (sNDA) to the FDA for the multikinase inhibitor cabozantinib (Cabometyx) as treatment for previously untreated patients with advanced renal cell carcinoma (RCC).

The sNDA is based on the phase II CABOSUN trial, in which 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).

“All of us at Exelixis are focused on improving care and outcomes for patients with cancer. Having successfully launched Cabometyx for patients with previously treated advanced RCC, the submission of this sNDA for Cabometyx as a treatment in the first-line RCC setting represents an important milestone for us,” Michael M. Morrissey, PhD, Exelixis president and CEO, said in a statement.

“If approved, Cabometyx will offer an important new alternative for the treatment of patients with previously untreated advanced RCC, having demonstrated a clinically meaningful and statistically significant progression-free survival benefit over sunitinib, a current standard of care. We would like to sincerely thank the study 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 bringing us one step closer to our goal of expanding the population of patients who may benefit from Cabometyx.”

From July 2013 and April 2015, researchers randomly assigned patients to 60 mg daily of cabozantinib (n = 79) or 50 mg daily of 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 overall survival 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, at 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 by the FDA 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.J Clin Oncol.2017;35(6):591-597. doi:10.1200/JCO.2016.70.7398.

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