FDA Approval Summary: Pralsetinib for the Treatment of Lung and Thyroid Cancers With RET Gene Mutations or Fusions

On September 4, 2020, the FDA granted accelerated approval for pralsetinib for non-small cell lung cancer (NSCLC), followed by approval on December 1, 2020, for thyroid cancer. This approval applies to: (i) adult patients with metastatic RET fusion-positive NSCLC, (ii) adult and pediatric patients aged 12 years and older with advanced or metastatic RET-mutant medullary thyroid cancer requiring systemic therapy, and (iii) adult and pediatric patients aged 12 years and older with advanced or metastatic RET fusion-positive thyroid cancer who require systemic therapy and are refractory to radioactive iodine (when appropriate). The approvals were based on data from a multicenter, open-label, multi-cohort clinical trial (ARROW, NCT03037385), which showed significant overall response rates (ORR) and lasting responses BLU-667 in patients with RET-altered tumors. In the approved patient groups, ORRs ranged from 57% (95% confidence interval [CI], 46-68) in those with RET fusion-positive NSCLC previously treated with platinum chemotherapy to 89% (95% CI, 52-100) in patients with RET fusion-positive thyroid cancer, with most responders experiencing a response duration of at least six months. The product label includes warnings and precautions regarding pneumonitis, hypertension, hepatotoxicity, hemorrhagic events, tumor lysis syndrome, potential impaired wound healing, and embryo-fetal toxicity. This article outlines the key factors considered during the FDA’s review that led to the approval of pralsetinib.