Cabozantinib Evokes Response in Some Clinical Trial Participants with Metastatic Pheo/Para

The results of a phase 2 clinical trial, the Natalie Trial, suggest that the drug cabozantinib may hold promise as a therapeutic option for some patients who have unresectable and progressive metastatic pheochromocytomas or paragangliomas (MPPGs). The trial found a 25% response rate from cabozantinib among those with MPPG, recently published in the journal Lancet Oncology.

Pheochromocytoma and paraganglioma (Pheo/Para) are neuroendocrine cancers that arise from cells in the adrenal glands (pheos) or outside of the adrenal glands in cells near nerve bunches called paraganglia (paras). The adrenal glands are located right above the kidneys and make hormones, such as the stress hormones epinephrine and norepinephrine.

Pheos and paras increase the production of these hormones, leading to hypertension and symptoms such as headaches, irritability, sweating, rapid heart rate, nausea, vomiting, weight loss, weakness, chest pain or anxiety.

MPPGs are rare, with 100 to 200 new cases diagnosed every year in the US.

Cabozantinib is a multi-tyrosine kinase inhibitor that targets specific proteins in cancer cells to help stop their growth and spread. It is also an antiangiogenic drug, working to disrupt the process by which tumors develop new blood vessels to fuel their growth.

The Natalie Trial, conducted at The University of Texas MD Anderson Cancer Center, included adults with histologically confirmed, progressive, and unresectable MPPGs. During the trial, 17 participants received oral cabozantinib at a dosage of 60 mg/day. Most participants experienced a reduction in tumor size and had their disease stabilized for longer periods. Participants with hormonally active tumors also saw improvements in their blood pressure compared to before starting treatment. These benefits were noted in participants with and without SDHB germline mutations.

Cabozantinib was associated with several adverse events, including hand-and-foot syndrome, hypertension, rectal fistula, QT prolongation, and low magnesium levels in the body. Dose reduction was used to successfully reduce side effects.

The study authors point to the need for larger randomized, placebo-controlled clinical trials to further assess the safety and efficacy of cabozantinib in participants with MPPGs. In addition, because MPPGs may develop resistance to cabozantinib, the authors note that clinical trials that combine the investigational drug with other therapies like immunotherapy should be considered.

Last year, positive results were reported from the Phase 3 CABINET trial evaluating cabozantinib in advanced neuroendocrine tumors, including pancreatic, gastrointestinal, and lung NETs. Interim data showed significant improvement in progression-free survival for advanced NETs that progressed on prior systemic therapies. While cabozantinib has been approved for other cancer types, it is not yet an FDA-approved therapy for neuroendocrine cancers.

NETRF is encouraged by ongoing clinical trials investigating new treatments for neuroendocrine cancer, which have the potential to provide patients with improved treatment options in the future.