FDA approves Gavreto for RET-altered thyroid cancers
The FDA granted accelerated approval to pralsetinib for treatment of certain patients with RET-altered thyroid cancer.
The approval applies to use of the agent by patients aged 12 years or older with advanced or metastatic RET-mutant medullary thyroid cancer who require systemic therapy, or those with RET fusion-positive thyroid cancer who require systemic therapy and are refractory to radioactive iodine.
Pralsetinib (Gavreto; Blueprint Medicines, Genentech) is a once-daily oral therapy designed to target oncogenic RET alterations.
The FDA previously approved the drug for treatment of adults with metastatic RET fusion-positive non-small cell lung cancer.
The agency based the thyroid cancer indication on results of the open-label, multicohort ARROW trial, in which researchers evaluated efficacy of the agent among patients whose tumors had RET gene alterations detected by next-generation sequencing, fluorescence in situ hybridization or other tests.
The trial included 55 patients with advanced or metastatic RET-mutant medullary thyroid cancer who received prior cabozantinib (Cabometyx, Exelixis) or vandetanib (Caprelsa, Sanofi Genzyme). In this cohort, researchers reported a 60% (95% CI, 46-73) overall response rate with pralsetinib, and 79% of patients achieved responses that lasted at least 6 months as determined by blinded independent review.
The trial also included 29 patients with RET-mutant medullary thyroid cancer who had not received cabozantinib or vandetanib. In this cohort, researchers reported a 66% (95% CI, 46-82) ORR and 84% of patients achieved responses that lasted at least 6 months.
Nine patients in the trial had RET fusion-positive thyroid cancer and were refractory to radioactive iodine. Eight of these patients (89%; 95% CI, 52-100) responded to pralsetinib, and all responses lasted at least 6 months.
The most common adverse events reported among pralsetinib-treated patients included constipation, hypertension, fatigue, musculoskeletal pain and diarrhea.
The most common grade 3 or grade 4 laboratory abnormalities included 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 FDA had granted priority review, breakthrough therapy and orphan drug designations to pralsetinib for the thyroid cancer indications.