On December 1, 2020, the FDA accelerated the approval of a new indication for pralsetinib (Gavreto; Blueprint Medicines), a RET kinase inhibitor, for the treatment of patients aged ≥12 years with advanced or metastatic medullary thyroid cancer and RET mutation who require systemic therapy or for patients with thyroid cancer and RET fusion who require systemic therapy and whose tumor is refractory to radioactive iodine, if radioactive iodine is appropriate.
The FDA granted pralsetinib priority review and orphan drug and breakthrough therapy designations for thyroid cancer with RET fusions. In September 2020, the FDA approved pralsetinib for metastatic non–small-cell lung cancer and RET fusions in adults.
The new indication was based on the overall response rate (ORR) and duration of response reported in the ARROW study, a multicenter, open-label, multicohort clinical trial of 55 patients with advanced or metastatic medullary thyroid cancer and RET alterations.
In the 55 patients with RET mutations who previously receive cabozantinib (Cabometyx) or vandetanib was 60%, with 79% of the responses lasting for ≥6 months. Among 29 patients with RET mutations who did not receive previous treatment with cabozantinib or vandetanib, and in 9 patients with thyroid cancer and RET fusion who were refractory to radioactive iodine the ORRs were 66% and 89%, respectively, and the responses lasted ≥6 months in 84% and 100% of the patients, respectively.
The most common (≥25%) adverse reactions with pralsetinib were constipation, hypertension, fatigue, musculoskeletal pain, and diarrhea. The most common (≥2%) grade 3 or 4 were decreased levels of lymphocytes, neutrophils, platelets, hemoglobin, decreased phosphate, calcium (corrected), and sodium, and increased levels of aspartate aminotransferase, alanine aminotransferase, and alkaline phosphatase.