Backed by Dana-Farber research, FDA approves new indication for a kidney cancer drug

A targeted drug whose clinical testing was led by Toni K. Choueiri, MD, of Dana-Farber Cancer Institute, has become a standard first-line therapy for certain newly diagnosed patients with advanced kidney cancer.

The drug, cabozantinib (CABOMETYX), was approved today by the U.S. Food and Drug Administration (FDA) for patients with previously untreated metastatic clear cell renal cell carcinoma (RCC) with intermediate or poor risk disease.

The benefits of cabozantinib for this group of patients were confirmed in the CABOSUN trial, a randomized Phase 2 multicenter study led by Choueiri comparing cabozantinib and sunitinib as initial treatment. The study was completed in 2015.

Individuals who received cabozantinib had a longer time to progression – the interval before their cancer worsened – than those taking sunitinib (Sutent), the drug that has been the standard initial treatment for metastatic kidney cancer for the past decade.

Metastatic clear cell renal cell carcinoma (RCC) is largely incurable, but researchers have identified factors used to classify patients as good, intermediate, or poor risk in terms of potential outcomes. The clinical trial included 157 patients, 81 percent considered to be intermediate risk and 19 percent poor risk, who had no previous treatment. In 36 percent of patients, the cancer had spread to the bone – a harbinger of worse outcome.

The most effective drugs for metastatic kidney cancer at present are agents that block angiogenesis by targeting vascular endothelial growth factor (VEGF) and its receptors. Such compounds are designed to interrupt blood supply to the tumors, slowing their growth or shrinking them. Both sunitinib and cabozantinib inhibit VEGF; cabozantinib also blocks the MET and AXL proteins, which are both involved in resistance to VEGF inhibitors.

The primary endpoint of the trial was progression-free survival, which was a median 8.2 months for cabozantinib and 5.6 months for sunitinib. Cabozantinib reduced the rate of disease progression or death by 34 percent compared with sunitinib. Responses were also higher with cabozantinib compared to sunitinib.

The trial wasn’t designed to compare overall survival rates between the drugs, but the researchers said preliminary data with a relatively short follow-up showed cabozantinib treatment was associated with a 20 percent decrease in the risk of death.