Efficacy of Selpercatinib in <i>RET</i> -Altered Thyroid Cancers
Lori J. Wirth, Eric J. Sherman, Bruce Robinson, Benjamin Solomon, Hyunseok Kang, Jochen H. Lorch, Francis P. Worden, Marcia S. Brose, Jyoti D. Patel, Sophie Leboulleux, Yann Godbert, Fabrice Barlési, John C. Morris, Taofeek K. Owonikoko, Daniel S.W. Tan, Oliver Gautschi, Jared Weiss, Christelle de la Fouchardière, Mark E. Burkard, Janessa Laskin, Matthew H. Taylor, Matthias Kroiß, Jacques Médioni, Jonathan W. Goldman, Todd M. Bauer, Benjamin Levy, Viola W. Zhu, Nehal J. Lakhani, Víctor Moreno, Kevin Ebata, Michele Nguyen, Dana Heirich, Edward Y. Zhu, Xin Huang, Luxi Yang, Jennifer Kherani, S. Michael Rothenberg, Alexander Drilon, Vivek Subbiah, Manisha H. Shah, Maria E. Cabanillas
Abstract
BACKGROUND: -altered thyroid cancers, the efficacy and safety of selective RET inhibition are unknown. METHODS: fusion-positive thyroid cancer, in a phase 1-2 trial of selpercatinib. The primary end point was an objective response (a complete or partial response), as determined by an independent review committee. Secondary end points included the duration of response, progression-free survival, and safety. RESULTS: fusion-positive thyroid cancer, the percentage who had a response was 79% (95% CI, 54 to 94), and 1-year progression-free survival was 64% (95% CI, 37 to 82). The most common adverse events of grade 3 or higher were hypertension (in 21% of the patients), increased alanine aminotransferase level (in 11%), increased aspartate aminotransferase level (in 9%), hyponatremia (in 8%), and diarrhea (in 6%). Of all 531 patients treated, 12 (2%) discontinued selpercatinib owing to drug-related adverse events. CONCLUSIONS: In this phase 1-2 trial, selpercatinib showed durable efficacy with mainly low-grade toxic effects in patients with medullary thyroid cancer with and without previous vandetanib or cabozantinib treatment. (Funded by Loxo Oncology and others; LIBRETTO-001 ClinicalTrials.gov number, NCT03157128.).