Ipsen’s and Exelixis’ Cabozantinib lowers disease progression and death rate by 31%

Ipsen and its partner Exelixis today announced detailed results from the CABOSUN randomized phase 2 trial of cabozantinib in patients with previously untreated advanced renal cell carcinoma (RCC) with intermediate- or poor-risk disease per the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC).

Ipsen said that CABOSUN was conducted by The Alliance for Clinical Trials in Oncology as part of Exelixis’ 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 percent reduction in the rate of disease progression or death [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 percent) improvement favoring cabozantinib over sunitinib. PFS 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 renal cell carcinoma patients 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.1

Objective response rate (ORR) was also significantly improved, at 46 percent (95% CI 34% – 57%) for cabozantinib versus 18 percent (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)].

“The results presented today support the potential of cabozantinib to become a new therapeutic option for previously untreated patients following their diagnosis with advanced kidney cancer,” said Toni K. Choueiri, M.D., Director, Lank Center for Genitourinary Oncology, Dana-Farber Cancer Institute and chair of the CABOSUN study. “Not only has cabozantinib surpassed sunitinib, the current standard of care, in progression-free survival and objective response rate, cabozantinib’s effects on progression-free survival were also consistently favorable across patient stratification subgroups including IMDC intermediate versus poor-risk groups and presence or absence of bone metastases.”

“We at the Alliance for Clinical Trials in Oncology are pleased that CABOSUN has successfully demonstrated that cabozantinib has the potential to benefit patients with advanced renal cell carcinoma as a first-line therapy,” said Michael J. Morris, M.D., Associate Member at Memorial Sloan Kettering Cancer Center, and Chair of the Alliance Genitourinary Committee. “We are grateful to everyone who has participated in the trial, especially the physicians, patients and their families.”

David Meek, Ipsen’s Chief Executive Officer stated: “Following the European commission approval of cabozantinib in second line advanced RCC, cabozantinib continues to show and expand potential clinical benefit in patients with RCC. With our partner Exelixis, we are pleased to report full results from the CABOSUN study showing superior results over sunitinib in PFS and ORR in patients with previously untreated advanced intermediate- or poor-risk RCC. Importantly the safety profile of cabozantinib is comparable to the sunitinib arm in the CABOSUN study as well as in previous studies of cabozantinib in advanced RCC. We look forward to sharing these important data with regulatory authorities and to define the path forward. ”

CABOSUN enrolled 157 patients with previously untreated advanced RCC: 80.9 percent of patients were intermediate risk per IMDC criteria and 19.1 percent were poor risk, 36.3 percent of patients had bone metastases, 46 percent of patients had ECOG Performance Status (PS) 0, 41 percent had ECOG PS 1, and 13 percent 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 PFS, 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 percent and 49 percent of patients, respectively. Discontinuation rate due to an adverse event was 20 percent with cabozantinib and 21 percent 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 percent of patients were hypertension (28 percent), diarrhea (10 percent), palmar-plantar erythrodysesthesia (8 percent), and fatigue (6 percent) in the cabozantinib arm, and hypertension (22 percent), fatigue (15 percent), diarrhea and thrombocytopenia (both 11 percent), and oral mucositis (6 percent) 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).