FDA Grants Approval to Cabometyx for First-Line Treatment of Advanced Renal Cell

Cancer Connect

The United States Food and Drug Administration (FDA) has approved the kinase inhibitor Cabometyx™ (cabozantinib) for the treatment of renal cell carcinoma (kidney cancer). The approval is for patients with advanced renal cell carcinoma who have already been treated with prior anti-angiogenic therapy. The FDA previously approved Cabometyx in 2016 for treatment of patients with advanced RCC who have received prior anti-angiogenic therapy. Today’s approval provides for treatment in the first-line setting.

Each year in the United States, more than 61,000 people are diagnosed with kidney cancer. The most common type of kidney cancer is renal cell carcinoma (RCC), which starts in the lining of very small tubes (tubules) in the kidney. For people with advanced or metastatic RCC (cancer that has spread to other parts of the body), targeted therapies can play an important role in treatment. Approximately 20-30% of patients with RCC will have metastases at diagnosis and as many as 40% will demonstrate metastasis after treatment for earlier stage RCC. With a 5-year survival rate ranging from 5-10% for patients with advanced RCC, the overall prognosis for these patients is poor.

About Cabometyx

Cabometyx™ is a kinase inhibitor that stops or decreases the action of many different cellular processes involved in cancer growth or spread. Cabometyx is thought to inhibit the action of the receptor tyrosine kinases including MET, VEGFR-1, -2, and -3, AXL, RET, ROS1, TYRO3, MER, KIT, TRKB, FLT-3, and TIE-2.

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

Preliminary data also showed that Cabometyx™ was associated with 20 percent lower risk of death during the study.

Toni K. Choueiri, MD, director of the Lank Center for Genitourinary Oncology at Dana-Farber, is lead author on a report in the Journal of Clinical Oncology summarizing results of the multicenter trial; senior authors are from Duke University Medical Center and Memorial Sloan Kettering Cancer Center.

“These results are very relevant to our practice and our kidney cancer patients – they may change the standard,” Choueiri said. “The results also demonstrate that studies sponsored by the National Cancer Institute can accrue rapidly and yield highly relevant results to the field.”

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 Sutent and Cabometyx™ inhibit VEGF; Cabometyx™ also blocks the MET and AXL oncogenes, both involved in resistance to VEGF inhibitors.

Cabometyx™, made by Exelixis, Inc., received Food and Drug Administration approval earlier in 2016 for second-line treatment of advanced kidney cancer. The current trial, known as A031203 CABOSUN, is comparing Cabometyx™ and Sutent as initial treatment.

The primary endpoint of the trial was progression-free survival, which was a median 8.2 months for Cabometyx™ and 5.6 months for sunitinib. Cabometyx™ reduced the rate of disease progression or death by 34 percent compared with sunitinib.

The overall response rate was better for Cabometyx™ patients, 46 percent of whom had complete or partial responses compared to 18 percent in the sunitinib group.

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 Cabometyx™ treatment was associated with a 20 percent decrease in the risk of death.

The safety and side effects profiles of the two drugs were similar and comparable to those observed in kidney cancer patients treated with other VEGF inhibitors, the investigators said. Patients stopped treatment because of adverse events at equivalent rates with the two drugs.

Cabometyx superior to Afinitor in advanced kidney cancer.

According to a recently published study in the New England Journal of Medicine, the targeted agent, Cabometyx, significantly improves the time to cancer progression and survival compared to Afinitor® (everolimus) in patients with advanced kidney cancer whose cancer has progressed following VEGRF-targeted therapy.

Researchers recently conducted a clinical trial in 658 patients with RCC whose cancer had progressed after VEGFR-targeted therapy. Patients were treated with either Cabometyx or Afinitor and directly compared.

The average time to cancer progression was 7.4 months for patients treated with Cabometyx, compared to only 3.8 months for those treated with Afinitor. Cabometyx was reasonably well tolerated, and longer follow up is required to ascertain the true overall survival benefit.(3)

Cabometyx is also approved for the treatment of medullary thyroid cancer and is marketed under the trade name Cometriq. Cometriq and Cabometyx have different formulations and are not interchangeable.


  1. Dana-Farber Cancer Institute. (2016.) New drug beats standard therapy in advanced kidney cancer. [Press release.] Can be accessed.
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  3. Choueiri T, Escudier B, Powles T, et al. Cabozantinib versus everolimus in advanced renal-cell carcinoma. New England Journal of Medicine. September 25, 2015 DOI: 10.1056/NEJMoa1510016.

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