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Cabozantinib Granted FDA Breakthrough Designation in Renal Cell Carcinoma

Jason M. Broderick @jasoncology
Published: Monday, Aug 24, 2015

Michael M. Morrissey, PhD

Michael M. Morrissey, PhD

Cabozantinib (Cometriq) has received a breakthrough therapy designation from the FDA for the treatment of patients with advanced renal cell carcinoma (RCC) following one prior therapy, according to Exelixis, the manufacturer of the multikinase inhibitor.

The designation is based on findings from the open-label, phase III METEOR study, in which cabozantinib reduced the risk of progression or death by 42% versus everolimus (HR, 0.58; P <.0001). Overall survival (OS) with cabozantinib was improved by 33% versus everolimus, with data continuing to mature (HR, 0.67; P = .005). Statistical significance for the OS endpoint was represented by a P value of .0019.

“Receiving breakthrough therapy designation is an important regulatory achievement for cabozantinib in renal cell carcinoma,” said Michael M. Morrissey, PhD, president and chief executive officer of Exelixis. “Following the positive top-line results announced in July and a productive dialogue with the FDA, Exelixis believes we can expedite our regulatory timelines and complete the cabozantinib NDA submission in advanced RCC prior to the end of 2015.”

METEOR randomized 658 patients with advanced RCC in a 1:1 ratio to received 60 mg of cabozantinib daily or 10 mg of everolimus daily. All patients had progressed following treatment with at least one prior VEGF TKI. The primary endpoint of progression-free survival (PFS) was assessed in the first 375 patients enrolled in the study. Analysis for OS and other secondary endpoints were from the full study population.

The trial was designed to show an HR for PFS of 0.67 and an HR for OS of 0.75. These statistical goals translate to an improvement in PFS of 2.5 months and an OS increase of 5 months with cabozantinib versus everolimus. However, given the data released by Exelixis, the actual improvement in OS and PFS appears better than estimates.

“We are eager to offer new treatment options for patients with metastatic RCC, particularly in the second-line setting where the most commonly utilized therapies have demonstrated a uniformly modest progression-free survival benefit,” METEOR trial principal investigator Toni K. Choueiri, MD, clinical director of the Lank Center for Genitourinary Oncology at Dana-Farber Cancer Institute, said in a statement when the findings were announced in July. “The magnitude of the improvement in PFS observed with cabozantinib compared to everolimus in the METEOR trial is an exciting and important development—it suggests an opportunity to improve care and outcomes for patients with metastatic RCC.”

In addition to efficacy data, the company noted that serious adverse events (AEs) were balanced between the cabozantinib and everolimus arms in the phase III study. In both arms, treatment discontinuation due to an AE was approximately 10%.

Exelixis reported that complete results from METEOR are scheduled for presentation as a late-breaking abstract on September 26 at the 2015 European Cancer Congress.

In April 2015, cabozantinib received a fast track designation from the FDA for patients with advanced RCC who had received one prior therapy. Under this program and the breakthrough designation, Exelixis is able to interact with the FDA more frequently. Additionally, the company can complete a rolling submission of data for a supplemental new drug application.

“We look forward to working closely with the FDA during the submission and review process, keeping in mind our ultimate goal of bringing a new therapeutic option to the renal cell carcinoma community as soon as possible,” said Morrissey.

The MET, VEGFR2, and RET inhibitor cabozantinib was approved by the FDA as a treatment for patients with metastatic medullary thyroid cancer in November 2012. The agent continues to be explored in a number of solid tumors.


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