New Drugs Show Promise Against Kidney Cancer

In an editorial published in the New England Journal of Medicine, Primo Lara, associate director for Translational Research at the UC Davis Comprehensive Cancer Center and David Quinn, medical director, USC Norris Cancer Hospital, highlight two new drugs that have shown great efficacy against kidney cancer.

 In two studies, also published in the Sept. 25 edition of the journal, researchers showed that nivolumab, an immunotherapeutic drug, and cabozantinib, a multikinase inhibitor, are more effective against advanced kidney cancer than a current standard of care. In the accompanying editorial, Lara and Quinn note that the positive results are “unequivocal.”
 
“These new drugs are clearly better than the older drug everolimus; they will soon find their place in the kidney cancer arsenal,” notes Lara. “Since these new agents are already approved for other indications, it is likely that their manufacturers will be applying to get FDA approval for kidney cancer soon.”
 
Currently, kidney cancer patients are first treated with an angiogenesis inhibitor, which restricts or reduces blood vessel growth into tumors. When that that therapy ceases to be effective patients are sometimes switched to everolimus, which inhibits mTOR, a master protein that controls a number of important cell growth pathways.
 
In the nivolumab study, called Checkmate, the median overall survival for patients treated with nivolumab was 25 months, compared to 19.6 months for those on everolimus. In addition, nivolumab reduced the risk of death by 27 percent and had far fewer side effects. Nivolumab is a checkpoint inhibitor, which takes the brakes off T-cells to help the immune system attack cancer. The drug is currently approved to treat advanced squamous cell lung cancer and metastatic melanoma.
 
In the cabozantinib study, called METEOR, the drug improved progression-free survival by nearly four months and showed a strong trend to improving overall survival. Cabozantinib is a multi-kinase inhibitor that affects several proteins associated with cancer progression and is currently approved to treat medullary thyroid cancer.
 
While these results are encouraging, the editorial noted some important caveats. Both trials failed to produce a significant number of complete responses, in which the cancer disappeared completely. There are also no good biomarkers that predict benefit from these agents.
 
“We need to expand the spectrum benefit by finding a biomarker that predicts which patient will preferentially benefit,” said Lara. “There seems to be a fixed number of patients who respond to immunotherapy – about 20 to 30 percent. We need to find markers that identify these patients. We also need to develop new combinations that broaden the group that benefits.”
 
The editorial also highlights another issue – value. These drugs are quite expensive, and the authors express their concerns that some patients will not have access due to inability to afford these pricey medicines.
 
“No treatment will work if patients do not get it,” said Lara. “And no patient will get it if it’s not affordable.”
 
Lara was a compensated member of the Independent Data Monitoring Committee for the METEOR trial.

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