CABINET Phase III trial confirms Cabometyx® efficacy in advanced neuroendocrine tumors

Ipsen announced today the final results from the CABINET Phase III trial, comparing Cabometyx® (cabozantinib) to a placebo in patients with advanced pancreatic neuroendocrine tumors (pNETs) and advanced extra-pancreatic neuroendocrine tumors (epNETs) who had experienced disease progression following prior systemic therapy. The findings revealed a significant reduction in the risk of disease progression or death for those treated with Cabometyx. Specifically, the risk reduction was 77% for advanced pNETs and 62% for advanced epNETs.

The data, presented at the 2024 European Society for Medical Oncology Congress (ESMO 2024) and published in the New England Journal of Medicine, indicated that Cabometyx offers a substantial improvement in progression-free survival (PFS). In patients with pNETs, median PFS was extended to 13.8 months compared to 4.4 months for those on placebo. For the epNET cohort, median PFS was 8.4 months versus 3.9 months for the placebo group. These results were determined by a blinded independent central review (BICR).

The safety profile of Cabometyx in this study was consistent with its known profile, and no new safety concerns were identified. The promising results have led Ipsen to submit an extension of indication for Marketing Authorization to the European Medicines Agency (EMA).

Teodora Kolarova, Executive Director of the International Neuroendocrine Cancer Alliance, emphasized the challenges faced by patients with neuroendocrine tumors, noting the importance of timely diagnosis and effective treatment options. She highlighted that these new data offer hope for significant advancements in therapy for this complex and often life-altering disease.

Christelle Huguet, EVP and Head of Research and Development at Ipsen, stated that the data reinforce the efficacy of Cabometyx in treating advanced stages of neuroendocrine tumors. Ipsen aims to shift the treatment paradigm through their submission to the EMA, leveraging their extensive experience in this area to provide new therapeutic options where they are critically needed.

The increasing incidence of neuroendocrine tumors is attributed to better awareness and improved diagnostic techniques, with approximately 35 per 100,000 people globally living with these tumors. However, due to the non-specific nature of symptoms, patients often see multiple specialists and undergo various tests before receiving an accurate diagnosis, which can take up to five years for nearly a third of patients.

Neuroendocrine tumors can develop in any part of the body and are generally slow-growing, though some can be aggressive. Treatment options depend heavily on the primary site of the disease, posing challenges in identifying the optimal care pathways for each patient. This necessitates multiple lines of therapy for disease progression.

Cabometyx works by inhibiting multiple receptor tyrosine kinases, including those involved in tumor angiogenesis, oncogenesis, metastasis, and drug resistance. Exelixis granted Ipsen exclusive rights to commercialize and further develop Cabometyx outside the U.S. and Japan, with Takeda holding similar rights in Japan. In over 65 countries, including the European Union, Cabometyx is approved for several indications, including advanced renal cell carcinoma and hepatocellular carcinoma.

Neuroendocrine tumors are relatively rare and arise from cells of the neuroendocrine system, most commonly found in the gastrointestinal tract, lungs, and pancreas. The five-year survival rates vary by the tumor's primary site, with advanced gastrointestinal and lung neuroendocrine tumors having survival rates of 68% and 55%, respectively. However, advanced pancreatic neuroendocrine tumors have a poorer prognosis with a five-year survival rate of 23%.

The CABINET trial, sponsored by the National Cancer Institute and led by the NCI-funded Alliance for Clinical Trials in Oncology, enrolled 298 patients who were randomized to receive either Cabometyx or a placebo. The primary endpoint was progression-free survival, with secondary endpoints including overall survival and radiographic response rate. Upon disease progression, patients on placebo could switch to open-label Cabometyx therapy. The trial's findings provide robust evidence supporting the use of Cabometyx in treating advanced neuroendocrine tumors, offering a new hope for improved patient outcomes in this challenging cancer type.