The safety profile of cabozantinib as a treatment for patients with advanced pancreatic neuroendocrine tumors in the phase 3 CABINET trial is comparable with previous reports of the agent.
Investigators will unblind and suspend the phase 3 CABINET trial (NCT03375320) after treatment with cabozantinib (Cabometyx) produced a considerable improvement in efficacy compared with placebo in previously treated patients with advanced pancreatic neuroendocrine tumors (NETs) or advanced extra-pancreatic NETs, according to a press release from Exelixis, Inc.
During the interim analysis, cabozantinib yielded a significantly longer duration without disease progression or death vs placebo across the trial’s cohorts. Based on these findings, the Alliance for Trials in Oncology independent Data and Safety Monitoring Board gave a unanimous recommendation for investigators to unblind the trial and cease their assessment. Investigators plan to share detailed results at a future medical meeting and discuss their findings with the FDA.
Treatment with cabozantinib in the CABINET trial did not produce any new safety signals, and its safety profile was comparable with prior reports of the agent.
“Patients with progressive [NETs] have limited treatment options,” study chair 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, said in the press release.
“At present, after progression on previous therapies, the treatment path is unclear, underscoring the need for additional options for this disease that is rising in incidence. These promising findings from the CABINET trial, in which cabozantinib showed an efficacy benefit for patients with pancreatic and extra-pancreatic neuroendocrine tumors, are welcome news and show the potential for cabozantinib to address important unmet needs for this community.”
Investigators of the double-blinded, randomized phase 3 CABINET trial assessed a total population of 290 patients, which included 93 with advanced pancreatic NETs and 197 with extra-pancreatic NETs. Patients were randomly assigned 2:1 to receive cabozantinib or matched placebo orally once a day on days 1 to 28 of each treatment cycle. Patients also underwent CT scans, MRIs, and/or x-rays during screening and while receiving study treatment. Those who were randomly assigned to the placebo arm were able to cross over to the cabozantinib arm if they experienced disease progression.
The trial’s primary end point was progression-free survival per RECIST v1.1 criteria as determined by retrospective independent central review. Secondary end points included overall survival, adverse effects, and radiographic response rate.
Patients 18 years and older with histologically documented pancreatic NETs by local pathology and locally advanced/unresectable or metastatic disease were eligible for enrollment on the trial. Additional eligibility criteria included having measurable disease per RECIST v1.1 criteria, disease progression after at least 1 line of FDA-approved therapy, and an ECOG performance status of 0 to 2.
Those with class III or IV congestive heart failure or clinically significant cardiac arrhythmia within 6 months of registration were not eligible to enroll on the trial. Patients were also unable to enroll if they had clinically significant gastrointestinal bleeding within 6 months of registration, radiological or clinical evidence of pancreatitis, known cavitary lung lesions, or a history of fracture within 28 days of registration.
“We are grateful for the recommendation of the Data and Safety Monitoring Board to unblind the CABINET study early due to a dramatic improvement in efficacy and look forward to discussing these findings with the [FDA],” Will Berg, MD, senior vice president of Medical Affairs at Exelixis, concluded.
Exelixis announces positive results from phase 3 CABINET pivotal trial evaluating cabozantinib in advanced pancreatic and extra-pancreatic neuroendocrine tumors. News release. Exelixis, Inc. August 24, 2023. Accessed August 28, 2023. https://shorturl.at/bP269