Toni K. Choueiri, MD
Cabozantinib (Cabometyx) reduced the risk of progression or death by 31% compared with sunitinib (Sutent) in the frontline setting for patients with metastatic renal cell carcinoma (RCC), according to results from the phase II CABOSUN trial presented at the 2016 ESMO Congress.
The median progression-free survival (PFS) was 2.6 months higher with cabozantinib versus sunitinib. The overall response rate (ORR) was 46% versus 18%, respectively.
“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,” principal investigator Toni K. Choueiri, MD, director, Lank Center for Genitourinary Oncology, Dana-Farber Cancer Institute, said in a statement.
“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,” added Choueiri.
Between July 2013 and April 2015, the open-label, randomized phase II CABOSUN trial enrolled 157 patients with intermediate- or poor-risk RCC. The Alliance for Clinical Trials in Oncology conducted the trial under a collaboration between Exelixis and the NCI’s Cancer Therapy Evaluation Program.
Enrolled patients had locally advanced or metastatic clear-cell RCC and an ECOG performance status of 0 to 2. Prior systemic therapy for RCC was not allowed. Patients were stratified by risk status and presence of bone metastases.
Patients were randomized in a 1:1 ratio to 60 mg once daily of cabozantinib (n = 79) or 50 mg once daily (4 weeks on, 2 weeks off) of sunitinib (n = 78). The primary outcome measure was PFS, with secondary endpoints including overall survival (OS) and ORR.
At a median follow-up of 20.8 months, 13 (16.46%) patients remained in the cabozantinib arm versus 2 (2.56%) patients in the sunitinib arm. The median PFS was 8.2 months (95% CI, 6.2-8.8) in the cabozantinib group compared with 5.6 months (95% CI, 3.4-8.2) in the sunitinib cohort (HR, 0.69; 95% CI, 0.48-0.98; P
At a median follow-up of 22.8 months, the median OS 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). “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,” Michael J. Morris, MD, associate member at Memorial Sloan Kettering Cancer Center and chair of the Alliance Genitourinary Committee, said in a statement. “We are grateful to everyone who has participated in the trial, especially the physicians, patients and their families.”
Grade ≥3 adverse events (AEs) occurred in 70.5% of the cabozantinib arm versus 72.2% of the sunitinib arm. Common grade ≥3 AEs included diarrhea (10% with cabozantinib vs 11% with sunitinib), fatigue (6% vs 15%), hypertension (28% vs 22%), palmar-plantar erythrodysesthesia (8% vs 4%) and hematological (2.6% vs 22.2%). There were 16 AE-related discontinuations in each arm.
“The past year has seen a tremendous level of progress in the treatment of kidney cancer, and we are excited to be at the forefront of bringing these advancements to patients,” Michael M. Morrissey, PhD, president and chief executive officer of Exelixis, said in a statement.
“Patients in the first-line setting with either intermediate- or poor-risk disease progress rapidly with sunitinib, a current standard of care; therefore, there is a clear need for new options that provide improved clinical benefit in this difficult to treat patient population. To that end, based on the CABOSUN results, we are planning to submit a supplemental new drug application in the United States for cabozantinib as a first-line treatment for advanced renal cell carcinoma,” added Morrissey.
Cabozantinib is approved in the United States and Europe as a treatment for patients with advanced RCC who have received prior antiangiogenic therapy.
Choueiri TK, Halabi S, Sanford B, et al. CABOzantinib versus SUNitinib (CABOSUN) as initial targeted therapy for patients with metastatic renal cell carcinoma (mRCC) of poor and intermediate risk groups: results from ALLIANCE A031203 trial. Presented at: 2016 ESMO Congress; October 7-11, 2016; Copenhagen, Denmark. Abstract LBA30.
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