Cabozantinib Improves Progression-Free Survival over Sunitinib for Metastatic Papillary RCC 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 during the 2021 American Society of Clinical Oncology Genitourinary Cancers Symposium, Dr. Sumanta K. Pal and colleagues reported on results comparing three tyrosine kinase inhibitors with activity on MET proto-oncogene signaling to sunitinib.

Among subtypes of RCC, clear cell is the most common and most well-studied histology in clinical trials, while pRCC makes up about 15% of RCC diagnoses. Inclusion of patients with pRCC in clinical trials can be variable, often without sufficient subgroup sample sizes to fully evaluate important clinical outcomes. Sunitinib represents a standard of care of the vascular endothelial growth factor targeted therapy era for RCC. However, other tyrosine kinase inhibitors may inhibit MET signaling, which has relevance for pRCC. Therefore, SWOG 1500 compared three potential candidates of cabozantinib, crizotinib, and savolitinib to sunitinib for patients with metastatic pRCC. The final sample included 152 patients. While patients were initially randomized equally to 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 demonstrated a PFS of 9.0 months, which was found to be 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 events: 68% for sunitinib vs. 74% for cabozantinib), the toxicity profiles were largely expected with similar rates reported in prior trials. The discontinuation rates were also similar at 24% for sunitinib and 23% for cabozantinib. Given the improved PFS with similar rates of adverse events, the authors concluded cabozantinib is the new reference standard for patients with metastatic pRCC.

References:

J Clin Oncol 39, 2021 (suppl 6; abstr 270)

Pal SK, Tangen C, Thompson IM Jr, et al. A comparison of sunitinib with cabozantinib, crizotinib, and savolitinib for treatment of advanced papillary renal cell carcinoma: a randomised, open-label, phase 2 trial. Lancet. 2021 Feb 20;397(10275):695-703.