In a recent phase 2 trial, Cabometyx showed longer progression-free survival than Sutent in patients with metastatic kidney cancer.
When compared with Sutent (sunitinib), Cabometyx (cabozantinib) reduced risk of progression or death by 31 percent in the frontline setting for patients with metastatic renal cell carcinoma (RCC). These findings, which were from the phase 2 CABOSUN trial, were presented at the 2016 European Society for Medical Oncology (ESMO) Congress.
The median progression-free survival (PFS) was 2.6 months higher with Cabometyx versus Sutent. The overall response rate (ORR) was 46 percent versus 18 percent, 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, M.D., 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 2 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 to 1 ratio to 60 mg once daily of Cabometyx (79 patients) or 50 mg once daily (four weeks on, two weeks off) of Sutent (78 patients). 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 percent) patients remained in the Cabometyx arm versus 2 (2.56 percent) patients in the Sutent arm. The median PFS was 8.2 months in the Cabometyx group compared with 5.6 months in the Sutent.
At a median follow-up of 22.8 months, the median OS was 30.3 months in the Cabometyx arm versus 21.8 months in the Sutent arm. “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, M.D., 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 or higher adverse events (AEs) occurred in 70.5 percent of the Cabometyx arm versus 72.2 percent of the Sutent arm. Common grade 3 or higher AEs included diarrhea (10 percent with Cabometyx vs 11 percent with Sutent), fatigue (6 percent vs 15 percent), hypertension (28 percent vs 22 percent), palmar-plantar erythrodysesthesia (8 percent vs 4 percent) and hematological (2.6 percent vs 22.2 percent). 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, Ph.D., 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.
Cabometyx is approved in the United States and Europe as a treatment for patients with advanced RCC who have received prior antiangiogenic therapy.