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FDA Approves Selpercatinib for Lung and Thyroid Cancers With RET Mutations or Fusions


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On May 8, 2020, the U.S. Food and Drug Administration (FDA) granted accelerated approval to selpercatinib (Retevmo) for the following indications:

  • Adult patients with metastatic RET fusion–positive non–small cell lung cancer (NSCLC)
  • Adult and pediatric patients ≥ 12 years of age with advanced or metastatic RET-mutant medullary thyroid cancer who require systemic therapy
  • Adult and pediatric patients ≥ 12 years of age with advanced or metastatic RET fusion–positive thyroid cancer who require systemic therapy and whose disease is refractory to treatment with radioactive iodine (if radioactive iodine is appropriate).

LIBRETTO-001

Efficacy was investigated in the multicenter, open-label, multi-cohort LIBRETTO-001 trial in patients whose tumors had RET alterations. Identification of RET gene alterations was prospectively determined in local laboratories using either next-generation sequencing, polymerase chain reaction, or fluorescence in situ hybridization. The main efficacy outcome measures were overall response rate and response duration determined by a blinded independent review committee using RECIST version 1.1.

Efficacy of selpercatinib therapy in RET fusion–positive NSCLC was evaluated in 105 adult patients previously treated with platinum chemotherapy. The overall response rate was 64% (95% confidence interval [CI] = 54%–73%); 81% of responding patients had responses lasting 6 months or longer. Efficacy was also evaluated in 39 patients who never received systemic treatment; the overall response rate for these patients was 85% (95% CI = 70%–94%) and 58% of responding patients had responses lasting 6 months or longer.

Efficacy of selpercatinib for advanced or metastatic RET-mutant medullary thyroid cancer was investigated in adults and pediatric patients ≥ 12 years of age. The trial enrolled patients previously treated with cabozantinib, vandetanib, or both, as well as patients who had not received these drugs. The overall response rate for the 55 previously treated patients was 69% (95% CI = 55%–81%); 76% of responding patients had responses lasting 6 months or longer. Efficacy was also evaluated in 88 patients not previously treated with an approved therapy for medullary thyroid cancer. The overall response rate for these patients was 73% (95% CI = 62%–82%); 61% of responding patients had responses lasting 6 months or longer.

Efficacy of selpercatinib for RET fusion–positive thyroid cancer was evaluated in adults and pediatric patients ≥ 12 years of age. The trial enrolled 19 patients who were radioactive iodine–refractory (if appropriate) and had received another prior systemic treatment, and 8 patients who were refractory to radioactive iodine and had not received any additional therapy. The overall response rate for the 19 previously treated patients was 79% (95% CI = 54%–94%); 87% of responding patients had responses lasting 6 months or longer. Efficacy was also evaluated in eight patients who received radioactive iodine and no other subsequent therapy. All eight patients had a response to treatment with selpercatinib (95% CI = 63%–100%) and 75% had responses lasting 6 months or longer.

The most common adverse reactions, including laboratory abnormalities (≥ 25%), were increased aspartate aminotransferase, increased alanine aminotransferase, increased glucose, decreased leukocytes, decreased albumin, decreased calcium, dry mouth, diarrhea, increased creatinine, increased alkaline phosphatase, hypertension, fatigue, edema, decreased platelets, increased total cholesterol, rash, decreased sodium, and constipation.

The recommended selpercatinib dose is weight-based—120 mg for patients weighing less than 50 kg and 160 mg for weighing 50 kg or more. Selpercatinib is taken orally twice daily with or without food or with food when co-administered with a proton pump inhibitor.


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