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
  • 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.

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