Exelixis Drug Halts Neuroendocrine Tumor Progression in Many Patients

A promising new treatment for neuroendocrine tumors may receive approval as early as April, following the presentation of final results from a Phase 3 study on Exelixis' cabozantinib at the European Society for Medical Oncology. The CABINET study investigated the efficacy of cabozantinib in two patient cohorts based on tumor location: pancreatic and extrapancreatic neuroendocrine tumors.

In patients with extrapancreatic neuroendocrine tumors, cabozantinib demonstrated a significant reduction in the risk of disease progression or death by 62% compared to a placebo. Similarly, in patients with pancreatic neuroendocrine tumors, the drug reduced the risk by 77%. The study concluded ahead of schedule due to these compelling findings, although researchers cautioned that early termination might result in an overestimation of the treatment's effectiveness. Despite this, the progression-free survival data in both patient groups were considered robust.

Exelixis currently markets cabozantinib under the names Cabometyx and Cometriq and reported $1.8 billion in sales from the drug last year. It is already approved for treating kidney, liver, and thyroid cancers, with a decision on its use for neuroendocrine tumors expected from the FDA by April 3.

Neuroendocrine tumors can develop anywhere in the body, leading to varied treatment protocols depending on tumor type and location. Current treatment options include somatostatin analogues like octreotide, everolimus, Novartis' radiopharmaceutical Lutathera, chemotherapy, and targeted therapies such as sunitinib. Each treatment is specific to certain patient subsets based on tumor properties. For instance, Lutathera is used in patients with particular somatostatin receptor levels, while sunitinib is reserved for pancreatic neuroendocrine tumors.

Dr. James Yao, a gastrointestinal oncologist at the University of Texas MD Anderson Cancer Center, highlighted that cabozantinib's approval could be particularly beneficial for patients with lung neuroendocrine tumors, who currently have limited treatment options, primarily everolimus.

The CABINET study was inclusive of patients regardless of their primary tumor location, provided they had undergone at least one prior therapy, with the median number of previous treatments being two or three. Dr. Jennifer Chan from the Dana-Farber Cancer Institute, the principal investigator of the study, emphasized the broad patient applicability of cabozantinib, noting its effectiveness across various patient groups.

In China, the tyrosine kinase inhibitor surufatinib is approved for both pancreatic and extrapancreatic neuroendocrine tumors. However, this drug was rejected by the FDA in the US in 2022, as its clinical trials were conducted exclusively in China.

The Phase 3 study by Exelixis revealed that median progression-free survival was 8.4 months on cabozantinib versus 3.9 months on placebo for extrapancreatic tumors, and 13.8 months compared to 4.4 months for pancreatic tumors, with statistically significant results (p<0.001) in both groups. The response rates were 5% and 19% for extrapancreatic and pancreatic tumors, respectively, compared to 0% for placebo.

Severe treatment-related adverse events included hypertension, fatigue, diarrhea, and thromboembolic events. A significant number of patients in both cohorts required dose reductions, with 31% and 20% discontinuing treatment due to adverse effects in the extrapancreatic and pancreatic groups, respectively.

Dr. Amy Peterson, Exelixis' medical chief, pointed out that gastrointestinal oncologists are already well-acquainted with cabozantinib due to its existing approvals in liver cancer and have experience managing its toxicities and necessary dose adjustments.

Despite some setbacks, such as the failure of Cabometyx to improve survival in a prostate cancer trial, Exelixis remains optimistic about its application for neuroendocrine tumors, with regulatory approval anticipated soon.