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

Cabozantinib extends advanced RCC overall survival

In continuation of my update on Cabozantinib

Patients with advanced or metastatic renal cell carcinoma (RCC) derive a significant overall survival (OS) benefit from second-line treatment with the multi-tyrosine kinase inhibitor (TKI) cabozantinib relative to everolimus.

These findings come from the final analysis of the phase III METEOR trial in which 330 participants were randomly assigned to receive cabozantinib 60 mg/day and 328 allocated to the mammalian target of rapamycin inhibitor everolimus at a dose of 10 mg/day. All patients had received at least one previous vascular endothelial growth factor receptor TKI.

After a median follow-up of 18.7 and 18.8 months in the cabozantinib and everolimus arms, respectively, the corresponding median OS times were 21.4 and 16.5 months, a significant difference equating to a hazard ratio for death of 0.66.

Progression-free survival was also significantly improved in the cabozantinib arm, as was the objective response rate - findings that were consistent with the previously reported results for the first 375 randomly assigned patients, report Toni Choueiri (Dana-Farber Cancer Institute, Boston, Massachusetts, USA) and team.

They conclude in The Lancet Oncology: "Based on these results, cabozantinib should be considered as a new standard-of-care treatment option for previously treated patients with advanced renal cell carcinoma."

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Ref : http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045%2816%2930107-3/abstract

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).

Patients with advanced kidney cancer benefit from cabozantinib treatment

In continuation of my update on cabozantinib

Patients with advanced kidney cancer live for nearly twice as long without their disease progressing if they are treated with cabozantinib, a drug that inhibits the action of tyrosine kinases - enzymes that function as an "on" or "off" switch in many cellular processes, including cancer.

In the second of two late-breaking presentations of research that is predicted to change the way kidney cancer patients are treated, Professor Toni Choueiri will tell the presidential session of the 2015 European Cancer Congress, about results from the first 375 patients out of a total of 658 patients recruited to the phase III clinical METEOR trial comparing cabozantinib with everolimus, the current standard treatment for the disease.

Analysis of results in July 2015 showed that the estimated median (average) progression-free survival time for patients with advanced clear cell kidney cancer, randomised to receive cabozantinib, was 7.4 months, while it was 3.8 months for those receiving everolimus. The objective response rate (the proportion of patients whose tumours shrank, assessed up to 17 months) was 21% for cabozantinib and 5% for everolimus.

An interim analysis of overall survival among all of the 658 patients found that it was a third better for patients receiving cabozantinib. The findings are published simultaneously with the ECC2015 presentation in the New England Journal of Medicine.

Prof Choueiri, who is Associate Professor of Medicine at Harvard Medical School and Clinical Director and Kidney Cancer Center Director at The Lank Center for Genitourinary Oncology, Dana-Farber Cancer Institute, USA, said: "I am very excited about the outcome of the study since the results may change the standard of care in patients with advanced kidney cancer who have received prior standard therapy that targets the vascular endothelial growth factor receptor (VEGFR).

"Although treatment with VEGFR-targeted drugs has been very effective in the first line of therapy for patients with advanced kidney cancer, in many cases tumour cells find ways to escape control by these drugs. Cabozantinib is a new drug that targets possible escape mechanisms of tumour cells, including the tyrosine kinases MET, VEGFR and AXL. The results of the METEOR trial indicate that cabozantinib is able to shrink tumours and slow down tumour growth much better than current standard treatment in patients who previously received VEGFR-targeted drugs. This has resulted in a significant reduction in the rate of disease progression or death in the cabozantinib arm as compared with the everolimus arm. Regaining tumour control after prior targeted therapy may reduce symptoms related to kidney cancer and eventually help patients live longer.

Patients with advanced kidney cancer benefit from cabozantinib treatment

Exelixis reports data from cabozantinib phase 3 trial on MTC

Exelixis, Inc. reported data from the phase 3 pivotal trial of cabozantinib in patients with progressive, unresectable, locally advanced or metastatic medullary thyroid cancer (MTC). The trial, known as EXAM, met its primary endpoint of improving progression-free survival (PFS), with patients in the cabozantinib (see structure) arm achieving a median PFS of 11.2 months compared with 4.0 months for patients in the placebo arm. Overall response rate (ORR), a secondary endpoint, was 28% in the cabozantinib arm and 0% in the placebo arm. Estimated PFS at one year was 47.3% with cabozantinib vs. only 7.2% with placebo. Data for overall survival (OS), another secondary endpoint, are not yet mature. Patients on the cabozantinib arm of the trial received a dose of 140 mg (free base equivalent). Adverse events were generally manageable allowing for treatment with cabozantinib for prolonged periods of time. Exelixis recently submitted a New Drug Application (NDA) for cabozantinib in MTC to the U.S. Food and Drug Administration (FDA).

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Exelixis reports data from cabozantinib phase 3 trial on MTC: Exelixis, Inc.  reported data from the phase 3 pivotal trial of cabozantinib in patients with progressive, unresectable, locally advanced or metastatic medullary thyroid cancer (MTC).