Monday, September 12, 2016

Exelixis Announces FDA Approval of Cabometyx (cabozantinib) for Patients with Advanced Renal Cell Carcinoma


In continuation of my update on  cabozantinib

Exelixis, Inc.   announced that the U.S. Food and Drug Administration (FDA) has approved Cabometyx (cabozantinib) tablets for the treatment of patients with advanced renal cell carcinoma (RCC) who have received prior anti-angiogenic therapy. RCC is the most common form of kidney cancer in adults. Cabometyx, which was granted Fast Track and Breakthrough Therapy designations by the FDA, is the first therapy to demonstrate in a phase 3 trial for patients with advanced RCC, robust and clinically meaningful improvements in all three key efficacy parameters — overall survival, progression-free survival and objective response rate.

“With  this announcement, patients with previously treated advanced kidney cancer now have a new option, the first and only approved product demonstrated to help patients live longer while also delaying the progression of their cancer,” said Michael M. Morrissey, Ph.D., president and chief executive officer of Exelixis. “We are proud to bring new hope to this community, who are looking for more therapies that can help extend lives. Exelixis is committed to making Cabometyx available to patients in need within the next couple weeks.”

“The efficacy profile demonstrated by Cabometyx in the METEOR trial, now complemented by the overall survival benefit, is highly compelling,” said Toni Choueiri, MD, Clinical Director, Lank Center for Genitourinary Oncology, Dana-Farber Cancer Institute. “Cabometyx is distinct from other approved treatment options, as it targets multiple tyrosine kinases involved in the development of RCC, including MET, AXL and three VEGF receptors. At the same time, physicians are very familiar with this class of drug and how to use dose adjustments to balance safety and efficacy. The approval of Cabometyx is wonderful news for physicians who are looking for a new option for their previously treated patients with advanced kidney cancer.”

The approval of Cabometyx is based on results of the phase 3 METEOR trial, which met its primary endpoint of improving progression-free survival. Compared with everolimus, a standard of care therapy for second-line RCC, Cabometyx was associated with a 42 percent reduction in the rate of disease progression or death. Median progression-free survival for cabozantinib was 7.4 months versus 3.8 months for everolimus (HR=0.58, 95% CI 0.45-0.74, P<0.0001). Cabometyx also significantly improved the objective response rate compared with everolimus. These data were presented at the European Cancer Congress in September 2015 and published in The New England Journal of Medicine.

As announced in February 2016, Cabometyx also demonstrated a statistically significant and clinically meaningful increase in overall survival in the METEOR trial. Compared with everolimus, Cabometyx was associated with a 34 percent reduction in the rate of death. Median overall survival was 21.4 months for patients receiving Cabometyx versus 16.5 months for those receiving everolimus (HR=0.66, 95% CI 0.53-0.83, P=0.0003).

The most common (frequency ≥25 percent) adverse reactions in Cabometyx-treated patients include diarrhea, fatigue, nausea, decreased appetite, hand-foot syndrome, high blood pressure, vomiting, weight loss, and constipation. Dose reduction rates were 60 percent for Cabometyx and 24 percent for everolimus. The rate of treatment discontinuation due to adverse reactions was low (10 percent in each arm) and consistent with that previously reported for everolimus.

About the METEOR Phase 3 Pivotal Trial

METEOR was an open-label, event-driven trial of 658 patients with advanced renal cell carcinoma who had failed at least one prior vascular endothelial growth factor (VEGF) receptor tyrosine kinase inhibitor (TKI) therapy. The primary endpoint was progression-free survival. Secondary endpoints included overall survival and objective response rate. The trial was conducted at approximately 200 sites in 26 countries, and enrollment was weighted toward Western Europe, North America, and Australia.

Patients were randomized 1:1 to receive 60 mg of Cabometyx daily or 10 mg of everolimus daily and were stratified based on the number of prior VEGF receptor TKI therapies received and on MSKCC risk criteria. No cross-over was allowed between the study arms.

Exelixis Announces FDA Approval of Cabometyx (cabozantinib) for Patients with Advanced Renal Cell Carcinoma

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