Targeting RET Alterations: Selpercatinib's Role in Pediatric Thyroid Cancer

Selpercatinib is a selective RET kinase inhibitor that’s been approved by the FDA for pediatric patients aged 2 years and older with advanced or metastatic RET-mutant medullary thyroid cancer who require systemic therapy or RET fusion-positive thyroid cancer who require systemic therapy and are radioactive iodine-refractory (if radioactive iodine is appropriate). It’s also approved for pediatric patients aged 12 years and older with advanced or metastatic RET fusion-positive solid tumors who have progressed following prior treatment or who have no satisfactory alternative treatment options.

This approval is significant as it provides a targeted therapy option for children with these rare and serious cancers, where previously treatment options may have been limited.

The efficacy and safety of selpercatinib in these pediatric populations were supported by the results of a clinical trial that showed a substantial response rate in patients with RET-driven cancers.

Here’s a quick review of that clinical trial data.

Efficacy Data

The FDA approval of selpercatinib for pediatric patients was based on data from the LIBRETTO-001 trial, which is a multicenter, open-label, multi-cohort clinical trial. The trial included pediatric patients with RET-driven solid tumors, like RET-mutant medullary thyroid cancer and RET fusion-positive thyroid cancer.

Key findings from the trial that supported the approval included:

• Objective response rate (ORR): The trial demonstrated a significant ORR, which is the proportion of patients with a partial or complete response to the therapy. The responses were also durable, meaning they lasted for a significant period of time.
• Efficacy across RET alterations: The trial showed that selpercatinib was effective in pediatric patients with different types of RET alterations, including both RET mutations and fusions.
• Age range: The trial included patients as young as 2 years old, demonstrating the drug's safety and efficacy in a young pediatric population.

These results from the LIBRETTO-001 trial provided compelling evidence that selpercatinib may be an effective treatment option for pediatric patients with these specific types of RET-altered thyroid cancers and solid tumors.

Safety Data

Selpercatinib, like all medications, can cause side effects, some of which can be serious. The most common side effects observed in clinical trials include elevated liver enzymes (AST/ALT), hypertension, fatigue, diarrhea, dry mouth, constipation, rash, abdominal pain, headache, prolonged QT interval on electrocardiograms (ECG), and edema.

Serious side effects may include the following:

• Hepatotoxicity: Liver function tests should be monitored before starting treatment, periodically during treatment, and as clinically indicated.
• Hypertension: Blood pressure should be controlled prior to initiating treatment and monitored regularly during treatment.
• QT Interval Prolongation: ECGs should be obtained prior to the initiation of selpercatinib, following any dose adjustments, and periodically during therapy.
• Hemorrhagic events: Serious, sometimes fatal, hemorrhagic events can occur. Patients should be monitored for signs and symptoms of bleeding.
• Hypersensitivity reactions: If a hypersensitivity reaction occurs, treatment should be discontinued, and appropriate medical therapy should be initiated.
• Tumor lysis syndrome: Patients with tumor burden should be monitored for signs and symptoms of tumor lysis syndrome and treated as clinically indicated.

Patients should be monitored for the development of these side effects, and dose modifications or treatment discontinuation may be necessary in the event of severe or intolerable side effects. It’s also important to discuss the potential side effects with patients and provide appropriate monitoring and management strategies to mitigate these risks.

From Trial to Treatment

With the FDA approval of selpercatinib, healthcare professionals now have a new treatment option to consider for appropriate pediatric patients based on their specific genetic alterations, previous treatments, and overall health status.

Reference:

Center for Drug Evaluation and Research. FDA grants accelerated approval to selpercatinib for pediatric patients two years and older with RET-altered metastatic thyroid cancer or solid tumors. U.S. Food and Drug Administration. May 29, 2024. Accessed June 5, 2024. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-selpercatinib-pediatric-patients-two-years-and-older-ret-altered.