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First-line cabozantinib shows significant benefit over sunitinib for metastatic kidney cancer
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Cabozantinib demonstrated a significant clinical benefit in PFS and overall response rate over standard-of-care sunitinib in previously untreated patients with intermediate- or poor-risk metastatic renal cell carcinoma, according to results of a randomized, phase 2, multicenter trial published in Journal of Clinical Oncology.
“The biggest takeaway from the CABOSUN trial was the statistically significant and clinically meaningful increase in PFS observed with cabozantinib [Cabometyx, Exelixis] vs. sunitinib [Sutent, Pfizer],” Toni K. Choueiri, MD, director of the Lank Center for Genitourinary Oncology at Dana-Farber Cancer Institute, told HemOnc Today. “Sunitinib has been a standard of care for first-line treatment of advanced clear cell renal cell carcinoma for over a decade, and no other agent has demonstrated superiority to sunitinib in this setting until now.”
Cabozantinib has a similar but broader mechanism of action compared with sunitinib, and both drugs inhibit the tyrosine kinase VEGFR-2, which blocks growth of blood vessels in the tumor, Choueiri said.
“Cabozantinib also inhibits two additional tyrosine kinases, MET and AXL, which are thought to play important roles in tumor progression,” he added. “The observed benefits suggest that targeting these additional pathways with cabozantinib improves the clinical outcome for patients with advanced renal cell cancer.”
The analysis included data from 157 adults with intermediate- (81%) or poor-risk (19%) clear cell metastatic renal cell carcinoma per International Metastatic Renal Cell Carcinoma Database Consortium criteria; all patients had an ECOG performance status of 0 to 2. Another 36% of patients had bone metastases.
Researchers randomly assigned patients to cabozantinib (n = 79; 60 mg once per day) or sunitinib (n = 78; 50 mg once per day, 4 weeks on, 2 weeks off).
PFS served as the study’s primary endpoint. Secondary endpoints included OS, ORR and safety.
Compared with sunitinib, cabozantinib treatment significantly increased median PFS (8.2 months vs. 5.6 months) and was associated with a 34% reduction in rate of progression or death (HR = 0.66; 95% CI, 0.46-0.95).
Patients treated with cabozantinib also showed a higher ORR (46%; 95% CI, 34-57) compared with patients assigned sunitinib (18%; 95% CI, 10-28). Each arm showed similar rates of grade 3 or 4 adverse events (cabozantinib, 67% vs. sunitinib, 68%), including diarrhea (10% vs. 11%), fatigue (6% vs. 15%), hypertension (28% vs. 22%), palmar-plantar erythrodysesthesia (8% vs. 4%) and hematologic adverse events (3% vs. 22%).
Additionally, grade 5 adverse events occurred in 5% (n = 4) of cabozantinib patients and 7% (n = 5) of sunitinib patients. Treatment-related grade 5 events occurring in three cabozantinib patients (acute kidney injury, sepsis, jejunal perforation) and three sunitinib patients (sepsis, respiratory failure, vascular disorders).
The effect of cabozantinib had on patients with bone metastases — who have reduced PFS and ORR compared with patients without bone metastases, and often have significant cancer-related symptoms — was particularly encouraging, Choueiri said.
“This subset of patients showed meaningful improvement with cabozantinib compared with sunitinib, demonstrating an almost doubling of median PFS in the CABOSUN trial in the cabozantinib arm,” Choueiri said. “Hence, treatment with cabozantinib would be an important option for renal cell cancer patients with bone metastases.”
Choueiri and colleagues noted favorable-risk patients were not included in the study and that could serve as a limitation, along with the fact that quality-of-life data were not collected.
The clinical trial success of cabozantinib and other recently approved agents represent another step in advancing the treatment of kidney cancer, Choueiri said.
“These new therapies have given physicians and patients with renal cell carcinoma more choices in how to manage their disease, but have raised additional questions about which therapies should be used in which patients,” he said. “In addition, ongoing clinical trials are testing whether combinations of new and existing therapies will give improved clinical outcomes in renal cell carcinoma. It is very likely that treatment of advanced renal cell carcinoma will continue to evolve and maybe very soon.” – by Chuck Gormley
For more information:
Choueiri can be reached at Dana-Farber Cancer Institute, 450 Brookline Ave, DANA 1230, Boston MA 02215; email: toni_choueiri@dfci.harvard.edu.
Disclosure: Choueiri reports honoraria from National Comprehensive Cancer Network and UpToDate; consultant roles with AstraZeneca, Bayer HealthCare Pharmaceuticals, Bristol-Myers Squibb, Cerulean Pharma, Eisai, Exelixis, Foundation Medicine, Genentech, Merck, Novartis, Pfizer, Peloton Therapeutics and Prometheus; and research funding from AstraZeneca, Bristol-Myers Squibb, Celldex, Exelixis, Genentech, Merck, Novartis, Peloton Therapeutics, Pfizer, Takeda Pharmaceuticals and TRACON Pharma. Please see the study for a full list of all other researchers’ relevant financial disclosures.
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