Toni K. Choueiri, MD
Cabozantinib (Cabometyx) significantly improved progression-free survival (PFS) compared with sunitinib (Sutent) in treatment-naive patients with advanced renal cell carcinoma (RCC) in the phase II CABOSUN trial, according to Exelixis, the developer of the multikinase inhibitor.
The safety profile for cabozantinib was similar to previously reported outcomes with the treatment in advanced RCC. Exelixis plans to submit the full CABOSUN results for presentation at an upcoming medical meeting and communicate with regulatory authorities about a potential first-line cabozantinib indication in RCC.
“The positive outcome of CABOSUN is extremely exciting, as it marks the very first time that a therapy has shown a progression-free survival benefit over standard of care first-line treatment sunitinib for patients with previously untreated advanced renal cell carcinoma,” Toni K. Choueiri, MD, clinical director, Lank Center for Genitourinary Oncology, Dana-Farber Cancer Institute, and chair of the CABOSUN study, said in a press release. “Based on these findings, cabozantinib may have the potential to become a new gold standard for previously untreated patients following their diagnosis with advanced kidney cancer.”
Between July 9, 2013, and April 6, 2015, the open-label, randomized phase II CABOSUN trial enrolled 157 patients with intermediate- or poor-risk RCC. 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 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). Patients were stratified by risk status and presence of bone metastases. The primary outcome measure was PFS, with secondary endpoints including overall survival (OS) and objective response rate. The Alliance for Clinical Trials in Oncology is conducting the trial under a collaboration between Exelixis and the NCI’s Cancer Therapy Evaluation Program (NCI-CTEP).
“All of us at the Alliance for Clinical Trials in Oncology are very gratified to have successfully demonstrated the potential of first-line cabozantinib to benefit patients with renal cell carcinoma in the CABOSUN study. This trial exemplifies how NCI-sponsored studies can be efficient, accrue rapidly, and yield results highly relevant to the field,” Michael J. Morris, MD, medical oncologist at Memorial Sloan Kettering Cancer Center, and Chair of the Alliance Genitourinary Committee, said in a statement.
Cabozantinib was previously approved in April 2016 as a treatment for patients with advanced RCC who have received prior antiangiogenic therapy.
The approval was based on findings from the 658-patient phase III METEOR trial, in which cabozantinib demonstrated a 42% reduction in the risk of progression or death compared with everolimus (Afinitor) in patients with advanced RCC. After a minimum of 11 months of follow-up, median PFS with cabozantinib was 7.4 months compared with 3.8 months with everolimus (HR, 0.58; 95% CI, 0.45-0.75; P
Cabozantinib also reduced the risk of death by 34% in the intent-to-treat population. Median OS was 21.4 months for patients receiving cabozantinib versus 16.5 months for those receiving everolimus (HR, 0.66; 95% CI 0.53-0.83; P
Commenting on the cabozantinib frontline data, Michael M. Morrissey, PhD, president and CEO of Exelixis, said, “Demonstrating an improvement in progression-free survival with cabozantinib compared to sunitinib as a first-line treatment represents an important milestone for patients with previously untreated RCC. We are thrilled to be a part of the many recent advances in the treatment of advanced kidney cancer and would like to thank the patients, physicians, nurses, caregivers, the Alliance cooperative group and NCI-CTEP who made this clinical trial possible. We look forward to pursuing next steps in the development of cabozantinib in the first-line treatment of patients with advanced RCC and other genitourinary malignancies.”