Cabozantinib Improves Progression-Free Survival versus Sunitinib in Patients with Metastatic Papillary Renal Cell Carcinoma in SWOG 1500

THE PHASE 2 SWOG 1500 trial demonstrated an improvement in progression-free survival (PFS) for cabozantinib over sunitinib among patients with metastatic papillary renal cell carcinoma (pRCC). In a presentation at the 2021 ASCOGenitourinary Cancers Symposium, Dr. Sumanta K. Pal (City of Hope Comprehensive Cancer Center, Duarte, CA) and colleagues reported the results of the study, which compared three MET (hepatic gowth factor receptor) inhibitors with sunitinib in pRCC. Among subtypes of RCC, pRCC makes up about 15% of diagnoses. Inclusion of patients with pRCC in clinical trials is inconsistent often with insufficient subgroup sample sizes to fully evaluate important clinical outcomes, the researchers noted.

Sunitinib has become a standard of care for vascular endothelial growth factor (VEGF) targeted therapy era for RCC. However other tyrosine kinase inhibitors may inhibit MET signaling, which has relevance for pRCC. SWOG 1500 compared three potential candidates, cabozantinib, crizotinib, and savolitinib, with sunitinib in patients with metastatic pRCC. Total enrollment was 152 patients, who were initially randomized equally to the treatment arms. A futility endpoint was met for crizotinib and savolitinib (median PFS, 3.0 and 2.8 months, respectively) where enrollment of additional patients was unlikely to demonstrate any difference compared to sunitinib (median PFS, 5.6 months).

Cabozantinib was associated with a PFS of 9.0 months, which was superior to sunitinib (hazard ratio, 0.60; 95% confidence interval, 0.37-0.97; P=0.019). While rates of adverse events were high (grade 3-4: 68% for sunitinib vs. 74% for cabozantinib), the toxicity profiles were largely expected with similar rates reported in prior trials. Dis- continuation rates were also similar at 24% for sunitinib and 23% for cabozantinib.

Given the improved PFS with similar rates of adverse events, the SWOG 1500 investigator concluded their findings supported cabozantinib as the new reference standard for patients with metastatic pRCC.

Hiten D. Patel, MD, MPH, completed residency training in urologic surgery at the James Buchanan Brady Urological Institute and is currently a Clinical Instructor and Fellow in Urologic Oncology at Loyola University Medical Center. He has published studies related to epidemiology, comparative effectiveness, evidence-based reviews, and clinical trials in urologic oncology and related fields.

Bibliography:

Pal SK, Tangen C, Thompson IM, et al. Sunitinib versus cabozantinib, crizotinib or savolitinib in metastatic papillary renal cell carcinoma (pRCC): Results from the randomized phase II SWOG 1500 study. J Clin Oncol. 2021;39(6, suppl 6):68. Abstract 270. doi: 10.1200/JCO.2021.39.6_suppl.270

Pal SK, Tangen C, Thompson IM Jr, et al. A comparison of sunitinib with cabozantinib, crizo- tinib, and savolitinib for treatment of advanced papillary renal cell carcinoma: a randomised, open-label, phase 2 trial. Lancet. 2021;397(10275):695-703. doi: https://doi.org/10.1016/ S0140-6736(21)00152-5