The antitumor activity of cabozantinib may not be limited to patients with clear cell renal cell carcinoma (RCC), according to an international, retrospective study published in Lancet Oncology.1

Multicenter data taken from patients with non-clear-cell histology indicated that a little less than one-third of patients achieved an objective response after undergoing oral cabozantinib therapy between 2015 and 2018. Patients with a variety of histologies were included, such as papillary (59%), chromophone (9%), duct histology (4%), Xp11.2 translocation histology (15%), and unclassified histology (13%).

According to study researcher Lauren C. Harshman, MD, of Dana-Farber Cancer Institute in Boston, Massachusetts, sunitinib is currently the most proven agent in non-clear cell disease, but beyond that, there are little data for the next best agent.

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“While we await the results of the ongoing prospective PAPMET study evaluating c-MET inhibitors such as cabozantinib in non-clear cell RCC, our results, which are based on a large collaborative effort across 22 centers, support the use of cabozantinib across the spectrum of non-clear cell cancers,” Dr Harshman told Cancer Therapy Advisor.

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Targeted agents against the VEGF and mTOR pathways were first proven effective in patients with clear cell RCC, and can be effective in non-clear cell histology but tend to have lower response rates and overall clinical benefit, according to Dr Harshman.

Cabozantinib inhibits multiple targets in addition to VEGF, such as c-MET and AXL, which may also help control the different types of disease that fall under the non-clear cell umbrella.

Cabozantinib is currently only approved by the US Food and Drug Administration for clear-cell RCC.

“Non-clear cell histologies were not thought to be VEGF-driven diseases and, thus, in the early trials, [researchers] did not want to dilute a possible efficacy signal in clear cell RCC where it made the most biologic sense,” Dr Harshman explained.

To examine the possible activity of cabozantinib in non-clear cell RCC, Dr Harshman and colleagues collected data from 112 patients treated with the drug at 22 centers in the United States and Belgium.

Overall, 27% of patients achieved an objective response to cabozantinib. There was one complete response and 29 partial responses. About half of patients (47%) had stable disease as best response.