"Cabozantinib should be considered the new reference standard for systemic therapy in patients with metastatic pRCC," Dr. Sumanta Pal, City of Hope, Duarte, California, said in presenting the results at the American Society of Clinical Oncology (ASCO) Genitourinary Cancers Symposium. The results were simultaneously published in The Lancet.
Papillary RCC is a rare malignancy, accounting for 15% of all RCC cases. The MET proto-oncogene is a key driver of pRCC. The SWOG 1500 trialists sought to determine whether the MET inhibitors cabozantinib, crizotinib or savolitinib could improve clinical outcome relative to sunitinib in patients with metastatic pRCC.
This open-label, phase 2 trial enrolled 147 eligible patients (median age, 66 years, 755 male) with pRCC from 65 cancer centers in the United States and Canada. They were randomly allocated to treatment with oral sunitinib, cabozantinib, crizotinib, or savolitinib, stratified by previous therapy and pRCC subtype.
Median PFS (primary outcome) was 9.0 months in patients taking cabozantinib versus 5.6 months in those taking sunitinib (hazard ratio, 0.60; 95% confidence interval: 0.37 to 0.97; 1-sided P=0.019), Dr. Pal reported.
Response rates (reduction in tumor size) were also significantly higher with cabozantinib than sunitinib (23% versus 4.0%; 2-sided P=0.010).
Regardless of subtype classification, cabozantinib has a "homogenous treatment effect across subtypes," Dr. Pal said.
Neither crizotinib nor savolitinib improved PFS compared with sunitinib and those study arms were terminated early at the time of an interim futility analysis.
Of the three MET inhibitors, cabozantinib has the "strongest affinity for MET and also blocks the VEGF receptor," the authors note in their Lancet paper.
The safety profiles of all four drugs were consistent with prior studies. Grade 3 or 4 adverse events occurred in 69% of patients receiving sunitinib, 74% of patients receiving cabozantinib, and 37% and 39%, respectively, of those receiving crizotinib and savolitinib; one grade 5 thromboembolic event was recorded in the cabozantinib group.
Dr. Stephanie Berg, with Loyola University in Chicago, who served as discussant for the trial, noted that papillary kidney cancer is "the most common subtype of non-clear-cell kidney cancer, accounting for about 15 to 20% of cases. The standard of care is sunitinib based on small prospective trials with progression-free survival ranging between two and eight months."
Based on the SWOG 1500 study, "We should consider cabozantinib as another first-line option for papillary renal cell carcinoma," she concluded.
Looking ahead, Dr. Pal and colleagues plan to study potential synergy between targeted treatments like cabozantinib and immune therapy in patients with papillary kidney cancer.
The SWOG 1500 study was supported by grants from the National Institutes of Health and National Cancer Institute. A complete list of author disclosures is available with the original article.
SOURCE: https://bit.ly/3pfZC05 Lancet, online February 13, 2021.
By Megan Brooks
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