Rare cancers are difficult to study in a clinical trial setting due to the relatively small number of patients. Two studies recently published in The Lancet Oncology examined the use of cabozantinib, an antiangiogenic multi-tyrosine kinase inhibitor, on two rare cancers: adrenocortical carcinoma, an endocrine cancer, and metastatic phaeochromocytomas and paragangliomas (MPPGs), both neuroendocrine tumors. Notably, these two cancers have just one FDA approved treatment each. The studies highlight the therapeutic potential of cabozantinib in combination with other therapies to improve outcomes for patients with rare cancers.
In a first prospective Phase II study, researchers led by Matthew Campbell, M.D., and Mouhammed Amir Habra, M.D., evaluated cabozantinib in 18 patients with adrenocortical carcinoma. Thirteen patients (72%) had progression free survival longer than four months, with a manageable safety profile consistent with cabozantinib use in other cancer types. The study supports further investigation of cabozantinib in combination with immune checkpoint inhibitors.
The Phase II Natalie Trial, led by Camilo Jimenez, M.D., examined the use of cabozantinib in 17 patients with MPPGs. Patients had an overall response rate of 25% with a median follow-up of 25 months. Cabozantinib was associated with tumor size reduction and prolonged disease stabilization. In all patients, the response was independent of their genotype, with 136 genes tested. However, MPPGs can develop resistance to cabozantinib, and 94% of patients discontinued participation due to disease progression. The study suggests cabozantinib merits further investigation in combination with targeted therapy or immunotherapy.