ESMO 2023: LBA53
Exelixis made headlines last month when its Cabometyx exceeded expectations in the treatment of neuroendocrine tumors (NETs), leading to an early termination of the trial. Now, the medical world gets a closer look at what one analyst had previously described as “dramatic improvements” in the data unveiled at the European Society for Medical Oncology Congress.
The Ipsen-partnered tyrosine kinase inhibitor underwent rigorous testing in a cohort of 290 participants, divided into two groups: one comprising patients with advanced pancreatic neuroendocrine tumors (pNETs) and the other with extra-pancreatic neuroendocrine tumors (epNETs).
In the pNET group, Cabometyx (cabozantinib) demonstrated its prowess by significantly extending the duration that patients lived without their disease progressing, achieving a median of 11.4 months, compared to a mere three months on the placebo. Equally remarkable results were observed in the epNET cohort, where Cabometyx nearly tripled the median progression-free survival when compared to the placebo, providing 8.3 months of relief compared to 3.2 months.
Named CABINET, the trial was prematurely halted and unblinded in August following a unanimous decision from an independent data and safety monitoring board.
In a disease category with limited treatment options, an approval for Cabometyx could be a game-changer. Exelixis reports that over 12,000 people in the US are diagnosed with NETs each year, with the incidence on the rise. NETs originating in the pancreas are often more aggressive, and at an advanced stage, the survival rate is a mere 23%.
“Although progress has been made in recent years, there remains a critical need for new and effective therapies for patients with advanced neuroendocrine tumors. Given that there is no standard treatment for patients with progressive disease, these results showing notable improvements in progression-free survival are highly encouraging for patients and their physicians.”
– Jennifer Chan, M.D., M.P.H., study chair for the CABINET trial and Clinical Director of the Gastrointestinal Cancer Center and Director of the Program in Carcinoid and Neuroendocrine Tumors at Dana-Farber Cancer Institute
William Blair analysts expressed their pleasant surprise at the trial’s success before the official release of data when the study was unblinded. They indicated that an FDA review in this disease setting is anticipated to take around a year.
In other developments, Cabometyx recently displayed mixed results in pretreated metastatic castration-resistant prostate cancer when administered as part of a combination therapy with Roche’s Tecentriq. Although the combination led to prolonged progression-free survival, overall survival rates did not meet statistical significance, despite a noticeable trend towards improvement.
Conclusion
The results from the CABINET study, reveal that treatment with cabozantinib has led to significant improvements in progression-free survival (PFS) for patients with pancreatic and extrapancreatic neuroendocrine tumors (pNET and epNET). These improvements were consistent whether assessed through local or independent central radiology reviews, indicating the robustness of the findings. The safety profile of cabozantinib remains in line with its known safety profile, with no new safety concerns identified.
These findings underscore the potential of cabozantinib as a promising treatment option for patients with advanced neuroendocrine tumors, especially those who may have previously received other therapies like somatostatin analogs, targeted therapies, Lu-177 dotatate, or chemotherapy. The substantial increase in PFS offers hope and improved outcomes for these patients, potentially expanding the therapeutic arsenal for neuroendocrine tumor management.
