Results from phase 2 CABOSUN trial of Cabozantinib ( Cabometyx ) versus Sunitinib ( Sutent ) in previously untreated advanced renal cell carcinoma were presented at the European Society for Medical Oncology ( ESMO ) 2016 Congress.
Cabozantinib met the primary endpoint of improving progression-free survival as compared to Sunitinib.
CABOSUN was conducted by The Alliance for Clinical Trials in Oncology as part of collaboration with the National Cancer Institute’s Cancer Therapy Evaluation Program ( NCI-CTEP ).
In CABOSUN, with a median follow-up of 20.8 months, Cabozantinib demonstrated a clinically meaningful and statistically significant 31% reduction in the rate of disease progression or death [ hazard ratio, HR=0.69, 95% CI ( 0.48-0.99 ), one-sided P=0.012 ].
The median progression-free survival ( PFS ) for Cabozantinib was 8.2 months versus 5.6 months for Sunitinib, corresponding to a 2.6 months ( 46% ) improvement favoring Cabozantinib over Sunitinib.
Progression-free survival benefits were independent of IMDC risk group ( intermediate or poor risk ) and presence or absence of bone metastases at baseline.
The results for Sunitinib were in line with a previously published retrospective analysis of 1,174 intermediate- and poor-risk patients with renal cell carcinoma from the IMDC database, which documented a median PFS of 5.6 months with a first-line targeted therapy, mainly Sunitinib, in this patient population.
Objective response rate ( ORR ) was also significantly improved, at 46% ( 95% CI 34% – 57% ) for Cabozantinib versus 18% ( 95% CI 10% to 28% ) for Sunitinib.
With a median follow up of 22.8 months, median overall survival was 30.3 months for Cabozantinib versus 21.8 months for Sunitinib [ HR=0.80, 95% CI ( 0.50 - 1.26 ) ].
CABOSUN enrolled 157 patients with previously untreated advanced renal cell carcinoma: 80.9% of patients were intermediate risk per IMDC criteria and 19.1% were poor risk, 36.3% of patients had bone metastases, 46% of patients had ECOG Performance Status ( PS ) 0, 41% had ECOG PS 1, and 13% had ECOG PS 2.
All patients were included in the efficacy analyses that followed the intent-to-treat principle.
Tumor assessments were performed by the investigators following RECIST criteria.
At the time of the analysis of the primary endpoint of progression-free survival, the median duration of treatment in CABOSUN was 6.9 months with Cabozantinib and 2.8 months with Sunitinib; 13 patients continued on Cabozantinib treatment versus 2 patients on Sunitinib treatment.
Dose reductions occurred for 58% and 49% of patients, respectively.
Discontinuation rate due to an adverse event was 20% with Cabozantinib and 21% with Sunitinib.
One hundred and fifty patients were evaluable for safety. Ninety-nine percent of patients on both arms experienced at least one adverse event.
The most common all causality grade 3 or 4 adverse events observed in more than 5% of patients were hypertension ( 28% ), diarrhea ( 10% ), palmar-plantar erythrodysesthesia ( 8% ), and fatigue ( 6% ) in the Cabozantinib arm, and hypertension ( 22% ), fatigue ( 15% ), diarrhea and thrombocytopenia ( both 11% ), and oral mucositis ( 6% ) in the Sunitinib arm.
Treatment-related grade 5 events occurred in three patients in the Cabozantinib arm ( acute kidney injury, sepsis and jejunal perforation ) and two patients in the Sunitinib arm ( sepsis and vascular disorder ).
CABOSUN was a randomized, open-label, active-controlled phase 2 trial that enrolled 157 patients with advanced renal cell carcinoma 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 progression-free survival. 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 cancinoma was not permitted. ( Xagena )
Source: Ipsen, 2016