Progression-free survival (PFS) was extended for patients with previously untreated, intermediate- or poor-risk advanced renal cell carcinoma (RCC) who were treated with Cabometyx (cabozantinib) compared to those treated with Sutent (sunitinib), according to results from a blinded, independent data review, which confirmed previous results from the CABOSUN trial.
Results from the randomized, open-label phase 2 CABOSUN trial were first presented at the 2016 ESMO Congress and published in the Journal of Clinical Oncology. Cabometyx reduced the risk of progression or death by 34 percent versus Sutent as a first-line treatment for patients with metastatic RCC. The median PFS was 2.6 months longer with Cabometyx versus Sutent, at 8.2 versus 5.6 months.
According to analysis by an independent radiology review committee, Cabometyx demonstrated a clinically meaningful and statistically significant reduction in the rate of disease progression or death as measured by PFS. Exelixis, manufacturer of cabozantinib, announced the findings in a press release.
“We are very pleased that CABOSUN’s primary endpoint of a statistically significant improvement of progression-free survival has been confirmed by the independent radiology review committee,” Michael M. Morrissey, Ph.D., Exelixis president and CEO, said in a release. “We continue in our focused efforts to complete the regulatory filing of cabozantinib for the treatment of patients with previously untreated advanced renal cell carcinoma and are on track to submit a supplemental new drug application in the third quarter of this year. Patients in the first-line setting with either intermediate- or poor-risk disease progress rapidly with sunitinib, a current standard of care, highlighting a clear need for new options that provide improved clinical benefit in this difficult-to-treat patient population.”
From July 2013 and April 2015, researchers randomly assigned patients to 60 mg daily Cabometyx (79 patients) or 50 mg daily Sutent (78 patients) for four weeks on followed by two weeks off. Eligible patients were required to have locally advanced or metastatic clear-cell RCC, ECOG performance status 0 to 2, and had to be intermediate or poor risk per the IMDC criteria. Prior systemic treatment for RCC was not permitted.
Median age across the entire patient population was 63 years (range, 31-87), 78 percent of patients were male, and 92 percent were white. Thirty-six percent of patients had bone metastases and 75 percent of patients had prior nephrectomy. Patients had an ECOG performance status of 0 (45.9 percent), 1 (41.4 percent) or 2 (12.7 percent).
Median OS was 30.3 months in the Cabometyx arm versus 21.8 months in the Sutent arm. Cabometyx was also superior for overall response rate (ORR), 46 percent versus 18 percent.
In 87 percent of the Cabometyx arm, there was some reduction in target lesions, compared with 44 percent of the Sutent cohort. The stable and progressive disease rates were 33 percent versus 36 percent and 18 percent versus 26 percent, respectively.
Adverse events (AEs) of any grade occurred in approximately 99 percent of each arm. The most common all-grade AEs with Cabometyx versus Sutent included fatigue (85.9 percent vs 81.9 percent), hypertension (80.8 percent vs 68.1 percent), diarrhea (71.8 percent vs 52.8 percent), increased AST (61.5 percent vs 31.9 percent) and increased ALT (55.1 percent vs 27.8 percent).
Grade 3 or higher AEs occurred in 66.7 percent of the Cabometyx arm versus 68.1 percent of the Sutent arm. Common grade 3 or higher AEs included diarrhea (10.3 percent with Cabometyx vs 11.1 percent with Sutent), fatigue (6 percent vs 15 percent), hypertension (28.2 percent vs 22.2 percent), palmar-plantar erythrodysesthesia (7.7 percent vs 4.2 percent) and fatigue (6.4 percent vs 15.3 percent).
Patients in the Cabometyx arm were more likely to require dose reductions, 58 percent versus 49 percent. There were 16 AE-related discontinuations in each arm.
Cabometyx is approved in the United States and Europe as a treatment for patients with advanced RCC who have received prior antiangiogenic therapy.