(HealthDay News) — For adults with papillary renal cell carcinoma (PRCC), the dual vascular endothelial growth factor (VEGF)-MET (hepatocyte growth factor receptor) inhibitor cabozantinib improves progression-free survival (PFS), according to a study published online in The Lancet to coincide with the American Society of Clinical Oncology annual Genitourinary Cancers Symposium, held virtually from Feb. 11 to 13.

Sumanta K. Pal, MD, from the City of Hope Comprehensive Cancer Center in Duarte, California, and colleagues randomly assigned 147 patients aged 18 years and older with metastatic PRCC who had received up to one previous therapy to receive either sunitinib, cabozantinib, crizotinib, or savolitinib.

The researchers found that after a prespecified futility analysis, assignment to the savolitinib and crizotinib groups was halted (29 and 28 patients, respectively); planned accrual for the sunitinib and cabozantinib groups was completed (46 and 44 patients, respectively). PFS was longer in the cabozantinib versus the sunitinib group (median, 9.0 vs 5.6 months; hazard ratio for progression or death, 0.60). The response rates for cabozantinib and sunitinib were 23 and 4%, respectively. There was no improvement in PFS for savolitinib and crizotinib versus sunitinib. Grade 3 or 4 adverse events occurred in 69, 74, 37, and 39% of patients who received sunitinib, cabozantinib, crizotinib, and savolitinib, respectively; one grade 5 thromboembolic event occurred in the cabozantinib group.

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“Our findings imply that PRCC might be driven by both VEGF-signalling and MET-signalling pathways, and thus might be more amenable to targeting with a dual VEGF-MET inhibitor such as cabozantinib,” the authors write

Several authors disclosed financial ties to pharmaceutical companies, including Exelixis, which manufactures cabozantinib.


Pal SK, Tangen C, Thompson Jr IM, 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. Published February 13, 2021. Lancet. doi:10.1016/S0140-6736(21)00152-5

Borchiellini D, Barthélémy P. Cabozantinib: a new first-line option for papillary renal cell carcinoma?
Published February 13, 2021. Lancet. doi:10.1016/S0140-6736(21)00316-0