Top-line results from the CABOSUN randomized phase 2 trial of Cabozantinib ( Cabometyx; Cometriq ) in patients with previously untreated advanced renal cell carcinoma ( RCC ) were announced.
The trial met its primary endpoint, demonstrating a statistically significant and clinically meaningful improvement in progression-free survival ( PFS ) for Cabozantinib compared with Sunitinib ( Sutent ) in patients with advanced intermediate- or poor-risk renal cell carcinoma.
The safety data in the Cabozantinib-treated arm of the study were consistent with those observed in previous studies in patients with advanced renal cell carcinoma.
CABOSUN is a randomized, open-label, active-controlled phase 2 trial that was designed to enroll 150 patients with advanced renal cell carcinoma determined to be intermediate- or poor-risk by the International Metastatic RCC Database Consortium ( 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 randomization was stratified by the IMDC risk strata ( intermediate or poor risk ) and presence of bone metastasis ( yes, no ). Enrollment was completed in March 2015.
The primary endpoint was progression-free survival, defined as time from randomization to disease progression or death, whichever occurs first.
Secondary endpoints included overall survival and objective response rate.
Eligible patients were required to have locally advanced or metastatic clear-cell renal cell carcinoma, ECOG performance status 0-2, and had to be intermediate or poor risk, per the IMDC Criteria ( Heng JCO 2009 ).
Prior systemic treatment for renal cell carcinoma was not permitted.
With 123 events ( disease progression or death ), the log-rank statistic has 85% power ( with a one-sided type I error rate=0.12 ) to detect a hazard ratio of 0.67.
Between July 9, 2013 and April 6, 2015, 157 patients were randomized: 79 patients on the Cabozantinib arm and 78 patients on the Sunitinib arm.
Cabozantinib targets include MET, AXL and VEGFR-1, -2 and -3. In preclinical models, Cabozantinib has been shown to inhibit the activity of these receptors, which are involved in normal cellular function and pathologic processes such as tumor angiogenesis, invasiveness, metastasis and drug resistance.
The American Cancer Society’s 2016 statistics cite kidney cancer as among the top ten most commonly diagnosed forms of cancer among both men and women in the U.S.
Clear cell renal cell carcinoma is the most common type of kidney cancer in adults. If detected in its early stages, the five-year survival rate for renal cell carcinoma is high; for patients with advanced or late-stage metastatic renal cell carcinoma, however, the five-year survival rate is only 12%, with no identified cure for the disease.
Approximately 30,000 patients in the U.S. and 68,000 globally require treatment.