New Management Option for RET Positive Thyroid Cancer

Efficacy for medullary thyroid cancer (MTC):
- Was evaluated in 55 adult and pediatric (older than 12 years) patients with advanced or metastatic RET-mutant MTC:
  - Who had previously been treated with cabozantinib, vandetanib, or both:
    - The ORR was 69%
- In addition, the drug was evaluated in 88 patients with advanced or metastatic RET-mutant MTC:
  - Who had not received prior treatment with cabozantinib or vandetanib:
    - The ORR for these patients was 73%
- The trial also enrolled 19 patients with RET-positive thyroid cancer whose condition was refractory to radioactive iodine (RAI) treatment and who had received another prior systemic treatment:
  - The ORR was 79%
- Eight patients had received only RAI:
  - The ORR for these patients was 100%
In all the cases of thyroid cancer:
- Among the patients who responded to treatment:
  - The response lasted longer than 6 months
RET alterations account for the majority of medullary thyroid cancers and a meaningful percentage of other thyroid cancers
A fact sheet from the company notes that RET mutations are found:
- In about 60% of sporadic MTC cases
- In over 90% of familial MTC cases
- RET fusions are found in approximately 10% to 20% of papillary thyroid cancers
The approval of selpercatinib means they now have a treatment option that selectively and potently inhibits RET
In the LIBRETTO-001 trial:
- The rate of discontinuations because of adverse reactions (ARs) was 5%
- The most common ARs, including laboratory abnormalities (≥ 25%), were:
  - Increased aspartate aminotransferase level
  - Increased alanine aminotransferase level
  - Increased glucose level
  - Decreased leukocyte count
  - Decreased albumin level
  - Decreased calcium level
  - Dry mouth
  - Diarrhea
  - Increased creatinine level
  - Increased alkaline phosphatase level
  - Hypertension
  - Fatigue
  - Edema
  - Decreased platelet count
  - Increased total cholesterol level
  - Rash
  - Decreased sodium levels
  - Constipation
- The most frequent serious AR (≥ 2%) was:
  - Pneumonia
The FDA warned that selpercatinib can cause:
- Hepatotoxicity, elevation in blood pressure, QT prolongation, bleeding, and allergic reactions
- It may also be toxic to a fetus or newborn baby so should not be taken by pregnant or breastfeeding women
The drug is currently being assessed in two phase 3 confirmatory trials:
- LIBRETTO-531 involves treatment-naive patients with RET-positive MTC.