Emerging Therapies in Pheochromocytoma and Paraganglioma: Immune Checkpoint Inhibitors in the Starting Blocks

Abstract

Pheochromocytoma and paraganglioma are neuroendocrine neoplasms, originating in the adrenal medulla and in parasympathetic and sympathetic autonomic nervous system ganglia, respectively. They usually present as localized tumours curable with surgery. However, these tumours may exhibit heterogeneous clinical course, ranging from no/minimal progression to aggressive (progressive/metastatic) behavior. For this setting of patients, current therapies are unsatisfactory. Immune checkpoint inhibitors have shown outstanding results for several types of solid cancers. We therefore aimed to summarize and discuss available data on efficacy and safety of current FDA-approved immune checkpoint inhibitors in patients with pheochromocytoma and paraganglioma. After an extensive search, we found 15 useful data sources (four full-published articles, four supplements of scientific journals, seven ongoing registered clinical trials). The data we detected, even with the limit of the small number of patients treated, make a great expectation on the therapeutic use of immune checkpoint inhibitors. Besides, the newly detected predictors of response will (hopefully) be of great helps in selecting the subset of patients that might benefit the most from this class of drugs. Finally, new trials are in the starting blocks, and they are expected to shed in the next future new light on a therapy, which is considered a milestone in oncology.

Bioinformatic analyses and experimental validation of the role of m6A RNA methylation regulators in progression and prognosis of adrenocortical carcinoma

“…These results indicated that the patients with high m6A risk may fail to benefit from ICIs treatment. It is noteworthy that the blockbuster results about the ICIs therapeutic effect on ACC remain unpublished, and several related trials, such as NCT04187404 and NCT02834013, are still ongoing [ 55 ]. Besides, differences in expression thresholds for defining PD-L1 positivity or overexpression make some contradictory results reported [ 31 ].…”

Immune Checkpoint Inhibitors: New Weapons Against Medullary Thyroid Cancer?

“…The therapeutic potential of FDA-approved atezolizumab, avelumab, ipilimumab and pembrolizumab has also been investigated in NENs other than MTC (39,40), thereby confirming a strong interest for ICI therapy in this subset of tumors.…”

Sunitinib Treatment for Advanced Paraganglioma: Case Report of a Novel SDHD Gene Mutation Variant and Systematic Review of the Literature

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