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 versus placebo 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 Cabometyx in pNETs (HR 0.23) and a 62% reduction in epNETs (HR 0.38).
Progression-Free Survival Benefits
The final results highlighted progression-free survival (PFS) benefits favoring Cabometyx. 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). For 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 in both cohorts was consistent with its known safety profile, and no new safety signals were identified.
Expert Commentary
Teodora Kolarova, Executive Director at the International Neuroendocrine Cancer Alliance, noted the challenges faced by individuals with neuroendocrine tumors, emphasizing the importance of timely diagnosis and optimal treatment options. She stated, "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."
Ipsen's Perspective
Christelle Huguet, EVP and Head of Research and Development at Ipsen, highlighted 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, harnessing our longstanding heritage in this area to deliver an effective new therapy where options are notably limited."
Disease Context
The incidence of NETs is increasing, with approximately 35 in every 100,000 people globally living with NETs. 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, underscoring the need for new therapies.
About the CABINET Trial
The CABINET trial, sponsored by the National Cancer Institute (NCI), is a Phase III study evaluating cabozantinib versus placebo in patients with advanced NETs after progression on prior therapy. The trial enrolled 298 patients and randomized them 2:1 to Cabometyx or placebo in two cohorts: pNET (n=95) and epNET (n=203). The primary endpoint was PFS per RECIST 1.1 by blinded independent central review.
About Cabometyx
Cabometyx (cabozantinib) is a small molecule that inhibits multiple receptor tyrosine kinases, including VEGFRs, MET, RET, and the TAM family, which are involved in cellular function and pathologic processes such as oncogenesis and tumor angiogenesis.
