Ipsen's Cabometyx (cabozantinib) has shown significant efficacy in treating advanced pancreatic and extra-pancreatic neuroendocrine tumors (NETs), according to final results from the CABINET Phase III trial. The data, presented at the European Society for Medical Oncology (ESMO) Congress 2024 and published in the New England Journal of Medicine, demonstrated a statistically significant and clinically meaningful reduction in the risk of disease progression or death compared to placebo.
The CABINET trial investigated Cabometyx in patients with advanced pNETs or epNETs whose disease had progressed after prior systemic therapy. The results indicated a 77% reduction in the risk of disease progression or death for patients with advanced pNETs (HR 0.23) and a 62% reduction for those with advanced epNETs (HR 0.38).
Progression-Free Survival Benefits
Final results demonstrated significant progression-free survival (PFS) benefits favoring Cabometyx over placebo, as assessed by blinded independent central review (BICR). In the pNET cohort, with a median follow-up of 13.8 months, 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). Similarly, in the epNET cohort, with a median follow-up of 10.2 months, the median PFS was 8.4 months for Cabometyx versus 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 both cohorts was consistent with its known safety profile, and no new safety signals were identified.
Addressing Unmet Needs in NET Treatment
"People living with neuroendocrine tumors face many challenges, from securing a timely diagnosis to optimal treatment options," said Teodora Kolarova, Executive Director, International Neuroendocrine Cancer Alliance. "These latest data reaffirm the possibilities of continuing scientific advancements in neuroendocrine tumors, offering the potential for new therapies which could significantly impact people’s everyday lives."
The incidence of NETs is rising, with approximately 35 in every 100,000 people living with NETs globally. Diagnosis is often delayed due to the non-specific nature of NET symptoms, leading to poorer patient outcomes. Treatment options are limited upon disease progression, varying based on the primary site of the tumor.
Mechanism of Action
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 cellular function and pathologic processes such as oncogenesis, metastasis, tumor angiogenesis, drug resistance, modulation of immune activities, and maintenance of the tumor microenvironment.
Regulatory Submission
Ipsen has submitted a Marketing Authorization application to the European Medicines Agency (EMA) seeking an extension of indication for Cabometyx in advanced NETs.
Christelle Huguet, EVP and Head of Research and Development at Ipsen, stated, "Through our submission to the EMA, it is our ambition to evolve the treatment paradigm for people living with neuroendocrine tumors, harnessing our longstanding heritage in this area to deliver an effective new therapy where options are notably limited."
