ITOG's Collaborative Research Leading to Major Breakthrough in Treatment of Thyroid Cancer
Monday, August 31, 2020
Posted by: Judy Dallas
It is with great pleasure to share that Dr. Lori Wirth, Dr. Eric Sherman, Dr. Bruce Robinson et al. (NEJM, Aug 27 2020) found that a phase 1-2 trial of selpercatinib, a selective RET-inhibitor, showed evident and durable efficacy in the treatment of patients with RET-altered thyroid cancer. Several ITOG members across the world made significant contribution in development and conduct of this multicenter pivotal trial that led to FDA approval of this drug in patients with RET-altered thyroid cancer in May 2020.
RET proto-oncogene encodes a transmembrane tyrosine kinase receptor that is important for intracellular signaling, mutations to which enable constitutive receptor activity and subsequent tumor growth and metastasis. Although 70% of medullary thyroid cancers are positive for RET mutations, there are currently no approved selective RET kinase inhibitors. Selectivity is important because the response to approved multi-targeted kinase inhibitors is limited by their systemic adverse effects, which is attributed to their non-RET targets.
In both RET-mutant medullary and RET fusion-positive thyroid cancer patients with and without previous treatment of multitargeted kinase inhibitors vandetanib or cabozanitib, selpercatinib, a selective RET kinase inhibitor (see figure), showed marked efficacy with little toxicity. Specifically, patients previously treated had a response rate of 69% and 1-year progression free survival of 82%, and in those patients not previously treated a response of 73% and 92%, respectively. Selpercatinib shows promise in ITOG’s collaborative efforts to develop and conduct both safe and effective therapies for thyroid cancer.
As Dr. Manisha Shah, Chair of ITOG, expressed, “The timeline of three years from the first patient in clinical trial to the FDA approval of this cancer drug is unprecedented in the history of drug development for thyroid cancer.”