Neuroendocrine tumor of pancreas

MONDAY, March 31, 2025 -- The U.S. Food and Drug Administration has approved cabozantinib (Cabometyx), an oral tyrosine kinase inhibitor, for patients with previously treated advanced neuroendocrine tumors, offering a new standard of care for this patient group, according to a press release from the Dana-Farber Cancer Institute. The approval was based on the results of the phase 3 CABINET study, which compared cabozantinib to a placebo in patients with advanced pancreatic neuroendocrine tumors and advanced extrapancreatic neuroendocrine tumors who had previously undergone treatment. The results of the trial were published last September in the New England Journal of Medicine . Patients treated with cabozantinib survived significantly longer with no worsening of their disease compared with patients who received placebo. Given the improved efficacy observed in the interim analysis, the trial was terminated early and unblinded in August 2023. The reported side effects of cabozantinib were similar to those found in other studies of the drug, including hypertension, fatigue, and diarrhea. "Patients with neuroendocrine tumors often face a difficult journey," lead author of the CABINET study, Jennifer Chan, M.D., M.P.H., of the Dana-Farber Cancer Institute, said in a statement. "Despite advances in recent years, there has remained a critical need for new and effective therapies for patients whose cancer has grown or spread. Cabozantinib significantly improved outcomes in this patient population and this FDA approval provides new hope." Approval of cabozantinib was granted to Exelixis. More Information Whatever your topic of interest, subscribe to our newsletters to get the best of Drugs.com in your inbox.

The US Food and Drug Administration (FDA) has approved Exelixis’ Cabometyx (cabozantinib) to treat advanced neuroendocrine tumours (NETs). The drug has been authorised for use in adult and paediatric patients aged 12 years and older with previously treated, unresectable, locally advanced or metastatic, well-differentiated pancreatic NETs or extra-pancreatic NETs. With an estimated prevalence of 380,000 in the US last year, NETs are tumours that arise from the neuroendocrine cells of the digestive tract and other organs, including the lungs and pancreas. Most NETs develop slowly over a number of years, but eventually all patients with advanced or metastatic NETs will experience refractory and progressive disease. Cabometyx is designed to block the action of tyrosine kinase enzymes, which can be found in certain receptors in cancer cells and help to send growth signals. The drug is already approved in the US to treat certain cases of renal cell carcinoma, hepatocellular carcinoma and differentiated thyroid cancer. The FDA’s latest decision was supported by positive results from the late-stage CABINET trial, which evaluated Cabometyx against placebo in patients with previously treated advanced pancreatic NETs or extra-pancreatic NETs. Cabometyx demonstrated continued improvement in the primary endpoint of progression-free survival (PFS). Among the pancreatic NETs cohort, median PFS was 13.8 months for Cabometyx versus 4.4 months for placebo after a median follow-up of 13.8 months. For those with extra-pancreatic NETs, median PFS was 8.4 months and 3.9 months for Cabometyx and placebo, respectively, at a median follow-up of 10.2 months. Study chair for the CABINET trial, Jennifer Chan, Dana-Farber Cancer Institute, said: “The characteristics of NETs vary widely from patient to patient, and very few treatment options have demonstrated the ability to improve outcomes across such a heterogeneous population. “… This FDA approval marks a meaningful advancement, which may establish an important new treatment option for patients, without limitations based on somatostatin receptor expression and functional status.” Exelixis holds the exclusive rights to develop and commercialise Cabometyx in the US, and has granted Ipsen exclusive rights to the drug outside of the US and Japan, and exclusive rights to Takeda in Japan.

Exelixis might soon have to test the FDA’s tolerance of a lackluster overall survival showing again for Cabometyx in prostate cancer. After canceling a planned advisory committee meeting, the FDA has approved Exelixis’ Cabometyx for neuroendocrine tumors.The small-molecule drug is now allowed for patients 12 years of age and older with previously treated, advanced, well-differentiated pancreatic or extra-pancreatic neuroendocrine tumors (pNET or epNET), the FDA said Wednesday.In an interesting and unusual item in Cabometyx’s updated label, the FDA acknowledges the potential impact that control arm patient crossovers may have had on Cabometyx’s patient survival results in a phase 3 trial.The approval could be an encouraging sign for oncology drug developers because, as the likes of Novartis know too well, the FDA has not been very receptive to companies using patient crossovers to justify a signal that may hint at a potential detriment to patient survival. Even though it doesn’t mean just any company with a crossover trial design can now expect to win over the FDA, Cabometyx serves as living proof that the agency is open to that line of reasoning.In Cabometyx’s case specifically, during an updated overall survival analysis of the phase 3 Cabinet trial that Exelixis used to support its NET bid, overall survival data favored placebo in both pNET and epNET patients.The overall survival data, which were immature, tallied 48% deaths in Cabometyx arm and 52% deaths in the placebo arm, but a preliminary 1% increased risk of death for the tyrosine kinase inhibitor in pNET patients. The numbers were 63% deaths for Cabometyx and 60% for placebo in epNET patients, resulting in a 5% higher risk of death for the active drug.The lackluster overall survival data came in stark contrast with the massive 78% and 60% progression-free survival improvements that Cabometyx has shown in the two patient subgroups, respectively. Sometimes such a disconnect between a major tumor progression benefit and muted overall survival showing could be attributed to nasty side effects harming the patients’ overall wellbeing. But in the Cabinet trial case, investigators and Exelixis have pointed to a high rate of patients in the control arm who crossed over to receive Cabometyx later upon disease progression. As the FDA label shows, 52% of pNET patients and 37% epNET participants in the control group got open-label Cabometyx, “which may impact the OS endpoint.”When the FDA unveiled a meeting of external experts to discuss Exelixis’ NET application, analysts suspected that the agency had questions about the survival data. The FDA then canceled the gathering in January.The medical community has been raving about Cabometyx in a hard-to-treat tumor type, in which patients face poor prognosis. In January, the National Comprehensive Cancer Network updated its guidelines to recommend Cabometyx as a category 1—the highest—preferred regimen for the majority of previously treated well-differentiated advanced NET, plus a category 2A backing for other forms of advanced NET.The current FDA approval is limited to well-differentiated NET even though the phase 3 Cabinet trial enrolled a small number of patients with moderately-differentiated cancers. In a Wednesday, March 26 press release, Exelixis noted that an estimated 161,000 to 192,000 people are living with unresectable, advanced NET, but the company didn’t break down how many are well-differentiated cases.NET can develop in any part of the body, but those that start in the gastrointestinal tract or in the lungs are the most common, while pNET can be more aggressive. By William Blair’s estimate, the entire NET market is expected to reach $4.6 billion by 2030.Also in NET, Exelixis is preparing to start a pivotal trial coded Stellar-311 to evaluate its investigational zanalintinib, a next-generation asset, versus Novartis’ Afinitor. Exelixis has high hopes for zanalintinib, having put its 2033 U.S. sales potential at $5 billion. With the NET nod in the pocket, Exelixis might soon have to test the FDA’s tolerance of a lackluster overall survival showing again. A combination of Cabometyx and Roche’s Tecentriq previously failed to deliver a statistically significant overall survival benefit compared with a change of novel hormonal therapy in metastatic castration-resistant prostate cancer in the final analysis of the Contact-02 trial. The study did meet its other dual primary endpoint, progression-free survival.Exelixis has said it intends to file an application with the FDA but has not done so. During a recent investors’ call, Exelixis management said the company will turn to the prostate cancer indication after it gets NET across the finish line.In response to a Fierce Pharma inquiry Wednesday, an Exelixis spokesperson said the company will provide an update on its regulatory plans at an appropriate time.