Final data from the CABINET Phase III trial reveal that Cabometyx® (cabozantinib) provides a statistically significant and clinically meaningful reduction in the risk of disease progression or death in patients with advanced pancreatic neuroendocrine tumors (pNETs) and extra-pancreatic neuroendocrine tumors (epNETs). The study, sponsored by the National Cancer Institute (NCI), was presented at the European Society for Medical Oncology (ESMO) Congress 2024 and published in the New England Journal of Medicine.
Significant Reduction in Disease Progression
The data demonstrated a 77% reduction in the risk of disease progression or death for Cabometyx compared to placebo in patients with advanced pNETs (HR 0.23) and a 62% reduction in patients with advanced epNETs (HR 0.38). These results highlight the potential of cabozantinib to address the unmet needs of patients with advanced NETs who have progressed after prior systemic therapy.
Progression-Free Survival Benefits
The trial results showed significant progression-free survival (PFS) benefits with Cabometyx versus placebo, as assessed by blinded independent central review (BICR). In the pNET cohort, the median PFS was 13.8 months for Cabometyx compared to 4.4 months for placebo (HR 0.23 [95% CI 0.12-0.42] p<0.0001). In the epNET cohort, the median PFS was 8.4 months for Cabometyx compared to 3.9 months for placebo (HR 0.38 [95% CI 0.25-0.59] p<0.0001).
Safety Profile
The safety profile of Cabometyx observed in each cohort was consistent with its known safety profile, and no new safety signals were identified.
Addressing Unmet Needs in NET Treatment
Neuroendocrine tumors (NETs) are relatively uncommon, arising from cells of the neuroendocrine system. Approximately 35 in every 100,000 people are living with NETs globally. Diagnosis can be challenging, with almost a third of patients taking at least five years to be diagnosed, leading to poorer outcomes. Treatment options are often limited upon progression, depending on the primary site of the disease.
Mechanism of Action of Cabometyx
Cabometyx (cabozantinib) is a small molecule that inhibits multiple receptor tyrosine kinases, including VEGFRs, MET, RET, and the TAM family (TYRO3, MER, AXL). These kinases are involved in oncogenesis, metastasis, tumor angiogenesis, drug resistance, modulation of immune activities, and maintenance of the tumor microenvironment.
About the CABINET Trial
The CABINET trial is a randomized, double-blinded Phase III trial of cabozantinib versus placebo in patients with advanced neuroendocrine tumors after progression on prior therapy. The trial enrolled 298 patients and was conducted by the NCI-funded Alliance for Clinical Trials in Oncology. The primary endpoint was PFS per RECIST 1.1 by retrospective independent central review.
Ipsen's Ambition
Christelle Huguet, EVP and Head of Research and Development at Ipsen, stated, "These latest data reinforce the potential of Cabometyx to deliver significant efficacy benefits at an advanced stage of disease. Through our submission to the EMA, it is our ambition to evolve the treatment paradigm for people living with neuroendocrine tumors."
