Clinical Activity of Selpercatinib in RET-mutant Pheochromocytoma.

Abstract

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.