Detailed results from phase III CABINET pivotal trial evaluating cabozantinib in advanced neuroendocrine tumors presented at ESMO 2023

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 data were presented during the Proffered Paper Session – NETs and Endocrine Tumours at the 2023 European Society of Medical Oncology (ESMO) Congress (LBA53) by the Alliance for Clinical Trials in Oncology.

“Although progress has been made in recent years, there remains a critical need for new and effective therapies for patients with advanced neuroendocrine tumors. Given that there is no standard treatment for patients with progressive disease, these results showing notable improvements in progression-free survival are highly encouraging for patients and their physicians,” said Dr. Jennifer Chan, study chairwoman for the CABINET trial and Clinical Director of the Gastrointestinal Cancer Center and Director of the Program in Carcinoid and Neuroendocrine Tumors at Dana-Farber Cancer Institute. “I am pleased to present these important findings at ESMO today, as they underscore the potential of cabozantinib as a much-needed new treatment option for this disease, which is rising in incidence.”

As announced in August, CABINET was stopped and unblinded early due to the dramatic improvement in efficacy observed at an interim analysis, per a unanimous recommendation of the Alliance for Clinical Trials in Oncology independent Data and Safety Monitoring Board (DSMB). The DSMB based their vote on data from interim analyses of PFS using local radiology assessments. Ancillary analyses were conducted using local and central assessments of patients enrolled through June 2023.

Results from the CABINET study presented at ESMO demonstrate that treatment with cabozantinib resulted in compelling improvements in PFS based both on local review and on independent blinded central radiology review. In the pNET cohort, at a median follow-up of 16.7 months, median PFS based on local radiology review was 11.4 months for patients receiving cabozantinib compared with 3.0 months for patients receiving placebo (stratified hazard ratio [HR]: 0.27; 95% confidence interval [CI]: 0.14-0.49; p<0.0001). the hr for pfs based on blinded independent central radiology review was 0.25 (95% ci: 0.12-0.54; p><0.0001). in the epnet cohort, at a median follow-up of 13.9 months, median pfs based on local radiology review was 8.3 months in patients receiving cabozantinib compared with 3.2 months for patients receiving placebo (stratified hr: 0.45; 95% ci: 0.30-0.66; p><0.0001). the hr for pfs based on blinded independent central radiology review was 0.50 (95% ci: 0.32-0.79; p><0.0001).

The safety profile of cabozantinib observed in each cohort was consistent with its known safety profile; no new safety signals were identified.

For patients with advanced NET, treatment options include somatostatin analogs, targeted therapy, Lu-177 dotatate, which is a form of peptide-receptor radionuclide therapy, or chemotherapy. Over half of patients in each cohort received prior everolimus or prior Lu-177 dotatate.

“We are pleased to share these details of cabozantinib in patients with advanced neuroendocrine tumors who have limited treatment options,” said Dr. Amy Peterson, Executive Vice President, Product Development & Medical Affairs and Chief Medical Officer, Exelixis. “We look forward to discussing . these findings wit the FDA so that we may potentially bring an active therapy to patients with these aggressive, difficult-to-treat cancers.”