Clinical Activity of Selpercatinib in RET-mutant Pheochromocytoma

Activating RET alterations have been reported in a variety of solid tumors, including pheochromocytoma where they occur both sporadically and as part of familial multiple endocrine neoplasia type 2 (MEN2) syndromes. Selpercatinib is a first-in-class, highly selective, and potent small molecule RET k...

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Bibliographic Details
Published in:The journal of clinical endocrinology and metabolism 2025-02, Vol.110 (3), p.e600-e606
Main Authors: Deschler-Baier, Barbara, Konda, Bhavana, Massarelli, Erminia, Hu, Mimi I, Wirth, Lori J, Xu, Xiaojian, Wright, Jennifer, Clifton-Bligh, Roderick J
Format: Article
Language:English
Subjects:
Adrenal Gland Neoplasms - drug therapy
Adrenal Gland Neoplasms - genetics
Adrenal Gland Neoplasms - pathology
Adult
Aged
Clinical
Female
Humans
Male
Middle Aged
Multiple Endocrine Neoplasia Type 2a - drug therapy
Multiple Endocrine Neoplasia Type 2a - genetics
Mutation
Pheochromocytoma - drug therapy
Pheochromocytoma - genetics
Protein Kinase Inhibitors - therapeutic use
Proto-Oncogene Proteins c-ret - antagonists & inhibitors
Proto-Oncogene Proteins c-ret - genetics
Pyrazoles - therapeutic use
Pyridines - therapeutic use
Treatment Outcome
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Summary:Activating RET alterations have been reported in a variety of solid tumors, including pheochromocytoma where they occur both sporadically and as part of familial multiple endocrine neoplasia type 2 (MEN2) syndromes. Selpercatinib is a first-in-class, highly selective, and potent small molecule RET kinase inhibitor that has demonstrated marked and durable antitumor activity in diverse RET-activated solid tumors in the LIBRETTO-001 study (NCT03157128). We describe the first 6 pheochromocytoma cases treated with selpercatinib in the LIBRETTO-001 study. Of the 6 patients (1 sporadic and 5 reported as part of MEN2 syndromes) in this case report, 4 had a partial response/complete response and 2 had stable disease per independent review committee. Treatment duration ranged from 9.2 months to more than 56.4 months. The safety profile of treatment was consistent with selpercatinib in other indications. These data support selpercatinib as an effective therapy against RET-mutant pheochromocytoma, adding to the diversity of RET-activated tumor types that may benefit from targeted RET inhibition.
ISSN:0021-972X
1945-7197
DOI:10.1210/clinem/dgae283