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A contemporary review of rearranged during transfection-selective inhibitors
Angel W Liu1, Connie Liang1, Chung-Shien Lee1,2
1College of Pharmacy and Health Sciences, Department of Clinical Health Professions, 4131St John's University, NY, USA.
Objective:
Rearranged during transfection genes are present in 1-2% of patients who have non-small cell lung cancer and 10-30% of patients with papillary thyroid cancer. The objective of this article is to review the current rearranged during transfection inhibitors indicated for patients with rearranged during transfection-mutated cancers and their future directions.Data sources: The pivotal phase I/II studies for selpercatinib and pralsetinib were evaluated. Current studies on rearranged during transfection inhibitors were searched on ClinicalTrials.gov using the key word "RET."Data summary: Selpercatinib and pralsetinib were the first two U.S. Food and Drug Administration-approved rearranged during transfection-selective inhibitors for advanced or metastatic rearranged during transfection fusion-positive non-small cell lung cancer, rearranged during transfection-mutant medullary thyroid cancer, and rearranged during transfection fusion-positive thyroid cancer. Both agents showed promising efficacy with objective response rate ranging from 60% to 73% in all aforementioned rearranged during transfection-mutated cancers. Additionally, benefits were seen even in patients with intracranial metastasis at baseline. Both showed favorable safety profiles. Some common class adverse events included elevated liver function tests and hypertension. Hematologic side effects such as anemia and neutropenia were more common with pralsetinib. Selpercatinib had interactions with acid suppressive therapy and specific instructions when used concomitantly.
Conclusions:
While the rearranged during transfection inhibitors are generally well-tolerated, each agent possesses slightly different efficacy, side-effect profile, and drug-drug interactions.
Insights
Rearranged during transfection (RET) inhibitors like selpercatinib and pralsetinib show high efficacy in RET-mutated cancers, including lung and thyroid cancers. These targeted therapies are generally well-tolerated, offering new treatment options.
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Background:
- Rearranged during transfection (RET) gene alterations occur in 1-2% of non-small cell lung cancer and 10-30% of papillary thyroid cancer.
- RET alterations drive tumor growth in specific subsets of lung and thyroid cancers.
Purpose of the Study:
- To review current RET inhibitors for RET-mutated cancers.
- To discuss future directions for RET-targeted therapies.
Main Methods:
- Evaluation of pivotal Phase I/II studies for selpercatinib and pralsetinib.
- Literature search on ClinicalTrials.gov for "RET" inhibitors.
Main Results:
- Selpercatinib and pralsetinib are FDA-approved RET-selective inhibitors for advanced RET-altered NSCLC and thyroid cancers.
- Objective response rates ranged from 60-73%, with benefits observed in patients with brain metastases.
- Both agents demonstrated favorable safety profiles, with distinct side effects and drug interactions noted for each.
Conclusions:
- RET inhibitors are generally well-tolerated and effective for RET-mutated cancers.
- Individual agents differ in efficacy, side effect profiles, and drug interactions, necessitating personalized treatment considerations.
