美国马萨诸塞州总医院Lori J. Wirth团队研究了selpercatinib治疗RET突变型甲状腺髓样癌患者的疗效。2020年8月27日，该研究发表在《新英格兰医学杂志》上。
Title: Efficacy of Selpercatinib in RET-Altered Thyroid Cancers
Author: Lori J. Wirth, M.D.,, Eric Sherman, M.D.,, Bruce Robinson, M.D.,, Benjamin Solomon, M.B., B.S., Ph.D.,, Hyunseok Kang, M.D.,, Jochen Lorch, M.D.,, Francis Worden, M.D.,, Marcia Brose, M.D., Ph.D.,, Jyoti Patel, M.D.,, Sophie Leboulleux, M.D.,, Yann Godbert, M.D.,, Fabrice Barlesi, M.D., Ph.D.,, John C. Morris, M.D.,, Taofeek K. Owonikoko, M.D., Ph.D.,, Daniel S.W. Tan, M.B., B.S., Ph.D.,, Oliver Gautschi, M.D.,, Jared Weiss, M.D.,, Christelle de la Fouchardière, M.D.,, Mark E. Burkard, M.D., Ph.D.,, Janessa Laskin, M.D.,, Matthew H. Taylor, M.D.,, Matthias Kroiss, M.D.,, Jacques Medioni, M.D., Ph.D.,, Jonathan W. Goldman, M.D.,, Todd M. Bauer, M.D.,, Benjamin Levy, M.D.,, Viola W. Zhu, M.D.,, Nehal Lakhani, M.D., Ph.D.,, Victor Moreno, M.D., Ph.D.,, Kevin Ebata, Ph.D.,, Michele Nguyen, B.S.,, Dana Heirich, M.S.N.,, Edward Y. Zhu, Ph.D.,, Xin Huang, Ph.D.,, Luxi Yang, M.P.H.,, Jennifer Kherani, M.D.,, S. Michael Rothenberg, M.D., Ph.D.,, Alexander Drilon, M.D.,, Vivek Subbiah, M.D.,, Manisha H. Shah, M.D.,, and Maria E. Cabanillas, M.D.
RET mutations occur in 70% of medullary thyroid cancers, and RET fusions occur rarely in other thyroid cancers. In patients with RET-altered thyroid cancers, the efficacy and safety of selective RET inhibition are unknown.
We enrolled patients with RET-mutant medullary thyroid cancer with or without previous vandetanib or cabozantinib treatment, as well as those with previously treated RET 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.
In the first 55 consecutively enrolled patients with RET-mutant medullary thyroid cancer who had previously received vandetanib, cabozantinib, or both, the percentage who had a response was 69% (95% confidence interval [CI], 55 to 81), and 1-year progression-free survival was 82% (95% CI, 69 to 90). In 88 patients with RET-mutant medullary thyroid cancer who had not previously received vandetanib or cabozantinib, the percentage who had a response was 73% (95% CI, 62 to 82), and 1-year progression-free survival was 92% (95% CI, 82 to 97). In 19 patients with previously treated RET 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.
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.