Ipsen's Cabometyx (cabozantinib) has shown significant efficacy in treating advanced pancreatic and extra-pancreatic neuroendocrine tumors (NETs), according to final data from the CABINET Phase III trial. The results, presented at the ESMO Congress 2024 and published in the New England Journal of Medicine, highlight a substantial 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 data demonstrated a 77% reduction in the risk of disease progression or death for Cabometyx versus placebo in advanced pNETs (HR 0.23) and a 62% reduction in epNETs (HR 0.38).
Progression-Free Survival Benefits
Final results demonstrated significant progression-free survival (PFS) benefits with Cabometyx compared to placebo, as assessed by blinded independent central review (BICR). In the pNET cohort, with a median follow-up of 13.8 months, median PFS was 13.8 months for Cabometyx versus 4.4 months for placebo (HR 0.23 [95% CI 0.12-0.42] p<0.0001). In the epNET cohort, with a median follow-up of 10.2 months, 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).
"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."
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.
Regulatory and Clinical Context
Ipsen has submitted an extension of indication Marketing Authorization to the European Medicines Agency (EMA). 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."
Neuroendocrine Tumors: An Overview
The incidence of NETs is increasing, with approximately 35 in every 100,000 people living with NETs globally. NETs can develop in various parts of the body, with the gastrointestinal (GI) tract, lungs, and pancreas being the most common sites. Diagnosis is often delayed due to the non-specific nature of NET symptoms, leading to poorer patient outcomes. Treatment options are limited, particularly after disease progression, highlighting the need for new therapies.
About 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.
