E-News - March 2025
Spotlight on Alliance Trials

:: Press Release ::

FDA Approves Drug for Patients with Previously Treated Advanced Neuroendocrine Tumors Based on Results from Alliance CABINET Trial

Today, the Alliance for Clinical Trials in Oncology was informed that the U.S. Food and Drug Administration has approved cabozantinib for the treatment of patients with previously treated advanced neuroendocrine tumors (NETs). NETs are a type of cancer that manifest characteristics of both nerve and hormone-producing cells, and can arise in various parts of the body, most commonly in the gastrointestinal tract, lungs, or pancreas. NETs affect patients in very different ways, and only a few treatments have been proven to improve outcomes for patients.

"This approval is exciting news as it gives us a new treatment option for patients with advanced neuroendocrine tumors,” said Jennifer Chan, MD, MPH, Clinical Director of the Gastrointestinal Cancer Center and Director of the Program in Carcinoid and Neuroendocrine Tumors at Dana-Farber Cancer Institute and Study Chair for the CABINET trial. “It was encouraging to see that cabozantinib resulted in significant delays in disease progression in a wide range of patients with advanced neuroendocrine tumors. This FDA approval is a major step forward for patients and their clinicians, offering a new standard of care for patients, who have long been in urgent need of effective treatment options."

The FDA approval is based on results from CABINET, a phase III pivotal trial evaluating cabozantinib compared with placebo in two groups of patients with previously treated NETs: one cohort of patients with advanced pancreatic neuroendocrine tumors (pNET) and a second cohort of patients with advanced extra-pancreatic NET (epNET). The study met the primary objective for each cohort, demonstrating that cabozantinib provided dramatic improvements in median progression-free survival (PFS) for the patients in the pNET and epNET cohorts.

The safety profile of cabozantinib observed in each cohort was consistent with those found in other studies of the drug. These include hypertension, fatigue, and diarrhea. No new safety signals were identified.

Final progression-free survival results were presented at the 2024 European Society for Medical Oncology Congress and published in The New England Journal of Medicine. In January 2025, the National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines in Oncology for Neuroendocrine and Adrenal Tumors were updated to include cabozantinib as a category 1 or 2A preferred treatment regimen for certain types of well-differentiated NETs, depending on primary tumor site, tumor grade, and prior therapy.

For patients with advanced NETs, the FDA approval of cabozantinib means that a new, effective treatment option is now available, offering the potential to slow disease progression. It will provide patients with more choices for managing their condition, especially when previous treatments have not been effective, and could lead to better overall outcomes for those with advanced stages of the disease.

About CABINET (Alliance A021602)

CABINET (Randomized, double-blinded phase III study of cabozantinib versus placebo in patients with advanced NETs after progression on prior therapy) is a multicenter, randomized, double-blinded, placebo-controlled phase III pivotal trial. This trial enrolled 298 patients in two separate cohorts (pNET and epNET) in the United States. Patients were randomized 2:1 into the cabozantinib or placebo arms of the study in each of the two cohorts. The trial was stopped early after an interim analysis showed superior efficacy associated with cabozantinib vs. placebo in each of the two cohorts. The trial included 99 patients with pNET and 199 patients with epNET. Patients with epNET had primary tumors arising in the gastrointestinal (GI) tract, lung, unknown primary sites, and other organs. Patients must have had measurable disease per RECIST 1.1 criteria and must have experienced disease progression after at least one FDA-approved line of prior therapy other than somatostatin analogs. The primary endpoint was PFS in each cohort. Upon confirmation of disease progression, patients were unblinded, and those receiving placebo were permitted to cross over to open-label therapy with cabozantinib. Secondary endpoints included overall survival, objective response rate and safety.

CABINET is sponsored by the National Cancer Institute (NCI), part of the National Institutes of Health (U10CA180821, U10CA180882), and led and conducted by the NCI-funded Alliance for Clinical Trials in Oncology with participation from the NCI-funded national clinical trials network (NCTN) as part of Exelixis’ collaboration with the National Cancer Institute’s Cancer Therapy Evaluation Program (NCI-CTEP) ); https://acknowledgments.alliancefound.org. To learn more about the CABINET trial, visit ClinicalTrials.gov.

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Reference: Alliance A021602: Randomized, double-blinded phase III study of cabozantinib versus placebo in patients with advanced neuroendocrine tumors after progression on prior therapy (CABINET). A full description of this clinical trial can be found at https://classic.clinicaltrials.gov/ct2/show/NCT03375320.