FDA Approves Pralsetinib for RET-Altered Thyroid Cancers

The FDA approved pralsetinib (Gavreto) for adults and children aged 12 or older with advanced or metastatic RET-mutant medullary thyroid cancer (MTC) who need systemic therapy or RET fusion-positive thyroid cancer who require systemic therapy and are radioactive iodine-refractory.

The approval is based on findings from the open-label, multi-cohort ARROW clinical trial, where the drug was administered to 55 patients with RET-mutant MTC who received prior cabozantinib or vandetanib. Overall response rate (ORR) was 60%, with 79% of responses lasting 6 or more months.

Additionally, pralsetinib was also evaluated in 29 patients with RET-mutant MTC who did not have previous cabozantinib or vandetanib. The ORR in this cohort was 66%, with 84% of responding patients having responses that lasted 6 months or longer. Finally, 9 patients who were radioactive iodine refractory received pralsetinib. Their ORR was 89%, and all responding patients had a response of 6 or more months.

It is recommended that pralsetinib be given orally once a day at a 400 mg dose. Patients should take the medication on an empty stomach, with no food intake at least 2 hours before and at least 1 hour after medication.

The most common adverse events, which occurred in 25% or more of patients included: constipation, hypertension, fatigue, musculoskeletal pain, and diarrhea.

Common grade 3-4 laboratory abnormalities, which occurred in at least 2% of patients were: decreased lymphocytes, decreased neutrophils, decreased hemoglobin, decreased phosphate, decreased calcium (corrected), decreased sodium, increased aspartate aminotransferase (AST), increased alanine aminotransferase (ALT), decreased platelets, and increased alkaline phosphatase.

The FDA made this approval 3 months ahead of schedule with the use of their Real-Time Oncology Review (RTOR) pilot program, as well as Assessment Aid.