LIBRETTO-531: A phase III study of selpercatinib in multikinase inhibitor-naïve RET-mutant medullary thyroid cancer Review


Authors: Wirth, L. J.; Brose, M. S.; Elisei, R.; Capdevila, J.; Hoff, A. O.; Hu, M. I.; Tahara, M.; Robinson, B.; Gao, M.; Xia, M.; Maeda, P.; Sherman, E.
Review Title: LIBRETTO-531: A phase III study of selpercatinib in multikinase inhibitor-naïve RET-mutant medullary thyroid cancer
Abstract: Selpercatinib is a first-in-class, highly selective and potent, central nervous system-active RET kinase inhibitor. In the phase I/II trial, selpercatinib demonstrated clinically meaningful antitumor activity with manageable toxicity in heavily pre-treated and treatment-naive patients with RET-mutant medullary thyroid cancer (MTC). LIBRETTO-531 (NCT04211337) is a multicenter, open-label, randomized, controlled, phase III trial comparing selpercatinib to cabozantinib or vandetanib in patients with advanced/metastatic RET-mutant MTC. The primary objective is to compare progression-free survival (per RECIST 1.1) by blinded independent central review of patients with progressive, advanced, multikinase inhibitor-naive, RET-mutant MTC treated with selpercatinib versus cabozantinib or vandetanib. Key secondary objectives are to compare other efficacy outcomes (per RECIST 1.1) and tolerability of selpercatinib versus cabozantinib or vandetanib. Selpercatinib (also known by the brand name Retevmo®/Retsevmo®) is a new treatment available in multiple countries for people with advanced or metastatic RET-mutant medullary thyroid cancer (MTC). Thyroid cancer starts in your thyroid gland and may spread or metastasize to other parts of the body, including lungs, bones, and occasionally the brain, which means the cancer is likely to be advanced. Advanced thyroid cancer can be driven by a gene in your body, one of which is RET. This is a summary of the LIBRETTO-531 study which compares selpercatinib, which is a strong and selective inhibitor of RET, with two approved drugs, cabozantinib and vandetanib. Patients with advanced or metastatic RET-mutant MTC who have not already received treatment with kinase inhibitors are being enrolled. This trial will evaluate how long people during and after treatment live with the disease without it getting worse. Selpercatinib may affect both healthy cells and tumor cells, which can result in side effects, which will also be evaluated in this study. This study is active and currently recruiting new patients. Clinical Trial Registration: NCT04211337 (ClinicalTrials.gov).
Keywords: genetics; pyridines; protein kinase inhibitor; randomized controlled trials as topic; protein kinase inhibitors; clinical trials, phase iii as topic; pyrazole derivative; pyrazoles; carcinoma; targeted therapy; thyroid neoplasms; protein ret; ret protein, human; proto-oncogene proteins c-ret; thyroid tumor; anilides; multicenter studies as topic; pyridine derivative; anilide; carcinoma, neuroendocrine; randomized controlled trial (topic); phase 3 clinical trial (topic); medullary thyroid cancer; multicenter study (topic); cabozantinib; humans; human; phase iii trial; ret mutation; selpercatinib; ret kinase inhibitor; ret alteration
Journal Title: Future Oncology
Volume: 18
Issue: 28
ISSN: 1479-6694
Publisher: Future Medicine  
Date Published: 2022-09-01
Start Page: 3143
End Page: 3150
Language: English
DOI: 10.2217/fon-2022-0657
PUBMED: 35969032
PROVIDER: scopus
DOI/URL:
Notes: Review -- Export Date: 1 November 2022 -- Source: Scopus
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  1. Eric J Sherman
    344 Sherman