Addressing Adverse Events from Kinase Inhibitors in Thyroid Cancer

Vivek Subbiah, MD, an associate professor in the Investigational Cancer Therapeutics department, discusses the adverse events (AEs) that come with the use of kinase inhibitors to treat patients with thyroid cancer.

Patients with thyroid cancer can have RET or other mutations that involve the kinase pathway and make kinase targeted inhibitors important for this patient population. However, kinase inhibitors can have significant AEs that impact how long the patient can be on the treatment to achieve a response.

Subbiah, medical director of the Clinical Center for Targeted Therapy, Cancer Medicine division at The University of Texas MD Anderson Cancer Center, discusses then how to manage these but also how new treatments like selpercatinib (Retevmo) can impact AEs in this patient population.

Transcription:

0:07 | These multi-targeted kinase inhibtors simultaneously target RET, in addition to a lot of other kinases [in thyrpid cancer]. Although the percentage of patients who had a response to these multikinase inhibitors were in anywhere from 12% to 65%, the safety and durability of the responses to these agents are partially limited by the off target AEs. These AEs like rash, diarrhea, and hypertension, lead to dose reductions in these patients, and these AEs are primarily attributed to more potent inhibition of non-RET kinases, as I said, the VGFR2. Previous to the entry of selective RET-inhibitors, no selective RET-inhibitor was approved for treating those patients.

1:03 | Selpercatanib is a novel ADP competitive, highly selective small molecule RET-kinase inhibitor. In preclinical models it showed nanomolar potential against diverse RET-alterations that included an acquired gatekeeper assistant mutation as well as anti-tumor activity in the brain. This acquired gatekeeper mutation is interesting because this can develop as a resistance mechanism to multi kinase inhibitors, or it is also seen in rare cases in germline patients with medullary thyroid cancer.