BARCELONA — A new treatment option for a wide range of patients diagnosed with neuroendocrine tumors could be approved in April, as final results of a Phase 3 study on Exelixis’ cabozantinib were presented Monday at the European Society for Medical Oncology.
The CABINET study included two cohorts of people with neuroendocrine tumors depending on the tumor location — in the pancreas or outside of it. In 203 patients with extrapancreatic neuroendocrine tumors, cabozantinib lowered the risk of disease progression or death by 62% compared to placebo. In a smaller cohort of 95 patients with pancreatic tumors, Exelixis’ drug cut the risk of disease progression or death by 77%.
The study had been stopped early at an interim analysis because of its compelling efficacy findings versus placebo. The trial investigators noted that the early termination of the study “could potentially lead to overestimation of the treatment effect,” though they added the progression-free survival analyses in both cohorts were “relatively mature,” according to a concurrent publication of the results in the New England Journal of Medicine.
Exelixis markets cabozantinib as Cabometyx and Cometriq, and last year the company generated $1.8 billion in sales from the tyrosine kinase inhibitor. The drug is approved for kidney cancer, liver cancer and thyroid cancer, and is awaiting an FDA decision in neuroendocrine tumors by April 3.
James YaoNeuroendocrine tumors can occur anywhere in the body, meaning existing treatment options vary from patient to patient. Treatment options include somatostatin analogues like octreotide, everolimus, Novartis’ radiopharmaceutical Lutathera, chemotherapy, and the targeted therapy sunitinib — but what’s available to patients depends on their tumor. For example, Lutathera is approved for patients with a certain level of somatostatin receptor expression, while sunitinib is used in patients with pancreatic neuroendocrine tumors only.
Gastrointestinal oncologist James Yao from the University of Texas MD Anderson Cancer Center told Endpoints News on the sidelines of the confab that for lung neuroendocrine tumor patients, this approval could be especially impactful because the only current go-to option for them is everolimus.
Patients were enrolled in Exelixis’ study regardless of where their primary tumor was, though they were required to have tried at least one previous therapy. The median number of previous treatments was two or three across the study cohorts.
“We were looking at a very broad group of patients … and we saw efficacy across the board,” Dana-Farber Cancer Institute neuroendocrine tumor specialist Jennifer Chan said. “This opens up options for a large number of patients. It’s not limited to just a small subset of patients.”
Chan, the principal investigator on the study, spoke to Endpoints ahead of her Monday presentation.
Yao noted that in China, the tyrosine kinase inhibitor surufatinib is approved for both pancreatic and extrapancreatic neuroendocrine tumors. The drug, developed by Hutchmed, was rejected in the US by the FDA in 2022 as its pivotal clinical trials were run in China.
More data from Exelixis
In Exelixis’ Phase 3 study, the median progression-free survival was 8.4 months on cabozantinib compared to 3.9 months on placebo in extrapancreatic tumors. In pancreatic neuroendocrine tumors, the median progression-free survival was 13.8 months compared to 4.4 months for placebo, with p<0.001 in both groups.
Also, the response rate was 5% and 19% in extrapancreatic and pancreatic neuroendocrine tumors, respectively, versus 0% with placebo.
The most common severe treatment-related adverse events were hypertension, fatigue, diarrhea, and thromboembolic events. Around two-thirds of patients in both the extrapancreatic and pancreatic groups on cabozantinib required dose reductions of the drug, and 31% and 20% of patients in the respective groups discontinued treatment due to adverse events.
Exelixis’ medical chief Amy Peterson said that because cabozantinib is already approved in liver cancer, gastrointestinal oncologists are already familiar with the drug. They’re also familiar with the toxicities and dose reductions needed for sunitinib, which is also a VEGF tyrosine kinase inhibitor.
In August, Exelixis announced that Cabometyx in combination with Tecentriq did not improve survival in a pivotal prostate cancer trial called CONTACT-02, details of which were shared at ESMO as well. Exelixis’ partner Ipsen, which has rights to Cabometyx outside of the US and Japan, announced Sunday that it does not plan to seek regulatory approvals based on the study.
Exelixis confirmed to Endpoints that it still plans to file for approval based on the prostate cancer study this year.