Pralsetinib Granted FDA Approval in Treatment of RET-Altered Thyroid Cancers
Posted: Wednesday, December 2, 2020
On December 1, the U.S. Food and Drug Administration (FDA) granted accelerated approval to pralsetinib (Gavreto) to treat adult and pediatric patients aged 12 years and older with advanced or metastatic RET-mutant medullary thyroid cancer who require systemic therapy or RET fusion–positive thyroid cancer who require systemic therapy and who have radioactive iodine–refractory disease. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.
The agency based its decision on efficacy data from the multicenter, open-label, multicohort ARROW trial, designed to evaluate pralsetinib in patients whose tumors had RET gene alterations. Efficacy was evaluated in 55 patients with advanced or metastatic RET-mutant medullary thyroid cancer who received prior cabozantinib or vandetanib. Patients in this cohort who were treated with pralsetinib demonstrated an overall response rate of 60%, with 79% of those patients experiencing a response that lasted at least 6 months.
Efficacy was also evaluated in 29 patients with RET-mutant medullary thyroid cancer who did not receive prior cabozantinib or vandetanib. Patients in this cohort who were treated with pralsetinib demonstrated an overall response rate of 66%, with 84% of those patients experiencing a response that lasted at least 6 months.
Lastly, efficacy for patients with RET fusion–positive thyroid cancer was evaluated in nine patients with radioactive iodine–refractory disease. The overall objective rate was 89%, with all patients experiencing responses lasting at least 6 months.
The most common adverse events included constipation, hypertension, fatigue, musculoskeletal pain, and diarrhea. The most common grade 3 or 4 laboratory abnormalities were decreased lymphocytes, decreased neutrophils, decreased hemoglobin, decreased phosphate, decreased calcium, decreased sodium, increased aspartate aminotransferase, increased alanine aminotransferase, decreased platelets, and increased alkaline phosphatase.
The recommended pralsetinib dose in adults and pediatric patients 12 years and older is 400 mg orally once daily on an empty stomach with no food intake for at least 2 hours before and at least 1 hour after taking pralsetinib.