Exelixis Announces U.S. FDA Approval of Cabometyx (cabozantinib) Tablets for Previously Treated Hepatocellular Carcinoma

In continuation of my update on Cabometyx (cabozantinib)

Exelixis, Inc. announced that the U.S. Food and Drug Administration (FDA) approved Cabometyx (cabozantinib) tablets for patients with hepatocellular carcinoma (HCC) who have been previously treated with sorafenib. HCC is the most common form of liver cancer and the fastest-rising cause of cancer-related death in the U.S. 

“This new indication for Cabometyx is an important treatment advance for patients with this aggressive form of liver cancer, a community in need of new therapeutic options,” said Michael M. Morrissey, Ph.D., President and Chief Executive Officer of Exelixis. “This approval is an important milestone as we continue to explore how Cabometyx may benefit people with difficult-to-treat-cancers beyond renal cell carcinoma. We would like to thank the patients and clinicians who participated in CELESTIAL and to acknowledge the team at the FDA for their continued collaboration during the review of our application.”

The FDA’s approval of Cabometyx was based on results from the CELESTIAL phase 3 pivotal trial of Cabometyx for patients with advanced HCC who received prior sorafenib. Cabometyx demonstrated a statistically significant and clinically meaningful improvement in overall survival (OS) versus placebo. On November 15, 2018, Exelixis’ partner Ipsen received approval from the European Commission for Cabometyx tablets as a monotherapy for HCC in adults who have previously been treated with sorafenib.

“Patients with this form of advanced liver cancer have few treatment options, particularly once their disease progresses following treatment with sorafenib,” said Ghassan K. Abou-Alfa, M.D., Memorial Sloan Kettering Cancer Center, New York and lead investigator on CELESTIAL. “Physicians are eager for new options for these patients, and the results of the CELESTIAL trial demonstrate that Cabometyx has the efficacy and safety profile to become an important new therapy in our efforts to slow disease progression and improve treatment outcomes.”

In the pivotal CELESTIAL trial, median OS was 10.2 months with cabozantinib versus 8.0 months with placebo (HR 0.76, 95 percent CI 0.63-0.92; p=0.0049). Median progression-free survival (PFS) was more than doubled, at 5.2 months with cabozantinib and 1.9 months with placebo (HR 0.44, 95 percent CI 0.36-0.52; p<0.0001). Objective response rates per RECIST 1.1 were 4 percent with cabozantinib and 0.4 percent with placebo (p=0.0086). Disease control (partial response or stable disease) was achieved by 64 percent of patients in the cabozantinib group compared with 33 percent of patients in the placebo group.

Adverse events in CELESTIAL were consistent with the known safety profile of cabozantinib. The most common (≥10 percent) grade 3 or 4 adverse events in the cabozantinib group compared to the placebo group were palmar-plantar erythrodysesthesia (17 percent vs. 0 percent), hypertension (16 percent vs. 2 percent), increased aspartate aminotransferase (12 percent vs. 7 percent), fatigue (10 percent vs. 4 percent) and diarrhea (10 percent vs. 2 percent). Treatment-related grade 5 adverse events occurred in six patients in the cabozantinib group (hepatic failure, esophagobronchial fistula, portal vein thrombosis, upper gastrointestinal hemorrhage, pulmonary embolism and hepatorenal syndrome) and in one patient in the placebo group (hepatic failure). Sixteen percent of patients in the cabozantinib arm and three percent of patients in the placebo arm discontinued treatment due to treatment-related adverse events.

“While we’ve seen some progress in the treatment of primary liver cancer in recent years, the patient community still needs new and better options,” said Andrea Wilson, President and Founder of Blue Faery: The Adrienne Wilson Liver Cancer Association. “The approval of Cabometyx has been eagerly anticipated, making this an important day for patients diagnosed with this devastating disease.”

In December 2018, Exelixis and its partner Ipsen announced the initiation of COSMIC-312, a phase 3 pivotal trial of cabozantinib in combination with atezolizumab versus sorafenib in previously untreated advanced HCC. The trial will also explore single-agent activity of cabozantinib in the first-line setting. For more information about the trial, visit ClinicalTrials.gov.

https://en.wikipedia.org/wiki/Cabozantinib



Exelixis Announces U.S. FDA Approval of Cabometyx (cabozantinib) Tablets for Previously Treated Hepatocellular Carcinoma

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).