The FDA granted accelerated approval to pralsetinib to treat with advanced or metastatic RET-mutant medullary thyroid cancer or RET fusion-positive thyroid cancer.
The 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 (MTC) who require systemic therapy or RET fusion-positive thyroid cancer who require systemic therapy and who are radioactive iodine-refractory.
The review of this application was conducted under the FDA’s Real-Time Oncology Review (RTOR) pilot program and Assessment Aid to assist the agency in approving the application 3 months ahead of the FDA goal date.
The agency based its decision on efficacy data from the multicenter, open label, multi-cohort ARROW clinical trial (NCT03037385), designed to evaluate pralsetinib in patients whose tumors had RET gene alterations.
Overall response rate (ORR) and duration of response (DOR) determined by a blinded independent review committee using RECIST 1.1 served as the main efficacy outcomes for the study.
Efficacy was evaluated in 55 patients with advanced or metastatic RET-mutant MTC who received prior cabozantinib (Cabometyx) or vandetanib (Caprelsa). Patients in this cohort who were treated with pralsetinib demonstrated an ORR of 60% (95% CI, 46%-73%), with 79% of those patients experiencing a response that lasted 6 months or longer.
Efficacy was also evaluated in 29 patients with RET-mutant MTC who did not receive prior cabozantinib or vandetanib. Patients in this cohort who were treated with pralsetinib demonstrated an ORR of 66% (95% CI, 46%-82%), with 84% of those patients experiencing a response that lasted 6 months or longer.
Lastly, efficacy for patients with RET fusion-positive thyroid cancer was evaluated in 9 patients who were radioactive iodine-refractory. The ORR was 89% (95% CI, 52%-100%), with all patients experiencing responses lasting 6 months or longer.
The most common adverse events (AEs) included constipation, hypertension, fatigue, musculoskeletal pain, and diarrhea. The most common grade 3-4 laboratory abnormalities were decreased lymphocytes, decreased neutrophils, decreased hemoglobin, decreased phosphate, decreased calcium, decreased sodium, increased aspartate aminotransferase (AST), increased alanine aminotransferase (ALT), decreased platelets, and increased alkaline phosphatase.
The FDA noted 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.
Of note, under accelerated approval, the application was based on overall response rate and duration of response. Therefore, continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.
FDA. FDA approves pralsetinib for RET-altered thyroid cancers Published: December 1, 2020. https://www.fda.gov/drugs/drug-approvals-and-databases/fda-approves-pralsetinib-ret-altered-thyroid-cancers?utm_medium=email&utm_source=govdelivery. Accessed: December 1, 2020.