Cabozantinib best remedy for metastatic papillary kidney most cancers

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Every month delayed in cancer treatment can raise risk of death by around 10%

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In a study by the SWOG Cancer Research Network that tested three targeted drugs, the small molecule inhibitor cabozantinib was found to be most effective in treating patients with metastatic papillary kidney cancer – results that are expected to change medical practice.

These results will be presented at ASCO's Virtual 2021 Genitourinary Cancers Symposium on February 13, 2021 at 1:00 p.m. ET. The results will be published simultaneously in The Lancet.

There are currently no effective treatments for metastatic papillary kidney cancer or metastatic pRCC, a rare subtype of kidney cancer. A study of 38 patients found that the average survival rate was eight months after diagnosis.

Sumanta Pal, MD, clinical professor of medical oncology at the City of Hope, a comprehensive cancer center, and researcher at SWOG, a clinical trial group funded by the National Cancer Institute (NCI), part of the National Institutes of Health (NIH) on cancer) said there is hope for patients with metastatic papillary kidney cancer. Mutations in the MET gene are a hallmark of this type of cancer, and new drugs are emerging that target the MET gene, among other important signaling pathways. Pal decided to test three of them against the current standard of care sunitinib, a receptor tyrosine inhibitor.

In its S1500 study, Pal looked at 147 eligible patients with papillary kidney cancer, most of whom had received no prior treatment. Patients were randomly assigned to one of four treatment groups – those taking sunitinib and those taking one of the three MET target drugs – cabozantinib, crizotinib, and savolitinib.

Pal and his team wanted to know how long it would take for patients' cancer to spread or return, a measure known as progression-free survival. What They Find: Patients who received sunitinib had a median of 5.6 months before their cancer got worse; Overall, patients who received savolitinib and crizotinib fared much worse. Cabozantinib, which in addition to MET also inhibits VEGF receptors and AXL, gave the patients a median of 9.2 months before their cancer got worse. In addition, 23% of the patients who took cabozantinib had a significant reduction in the size of their tumor. In contrast, only 4% of patients saw such a tumor reaction with sunitinib.

"The magnitude of the response was surprising," said Pal. "We still have a long way to go to make patient lives longer and better, but we have a new standard of care for these rare cancer patients. This result is testament to SWOG and City of Hope who have the motivation and expertise required for the successful conduct of rare clinical cancer studies. "

Building on the momentum from S1500, SWOG will lead the next pivotal study in papillary kidney cancer, focusing on the potential synergies between targeted treatments such as cabozantinib and immunotherapy. Pal will conduct this study with SWOG researcher Dr. Benjamin Maughan at the University of Utah's Huntsman Cancer Institute.

SWOG 1500, also called PAPMET, was sponsored by NCI, by the SWOG Cancer Research Network under the direction of Dr. Pal designed and directed and conducted through the NCI's National Clinical Trials Network.

S1500 was also funded by the NIH through NCI grants CA180888, CA180819, CA180820, CA180821, CA180863, and CA180868. and in part from AstraZeneca plc / AB, Exelixis, Inc., and Pfizer, Inc. The companies made savolitinib, cabozantinib, crizotinib and sunitinib, respectively, available for study under each company's collaboration agreement with the NCI.

"NCI's drug development program as part of the Cancer Therapy Evaluation Program facilitated collaboration between pharmaceutical companies, as well as collaboration between companies and SWOG researchers, to make this study possible. We are proud to have helped define this therapy for patients with papillary renal cell carcinoma "said Dr. John Wright, Associate Branch Chief of CTEP's Investigational Drug Branch and NCI Medical Monitor for the study.

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