Pralsetinib: Treatment of metastatic RET fusion-positive non-small cell lung cancer

Purpose. To review the pharmacology, efficacy, safety, dosing and administration, and place in therapy of pralsetinib, a tyrosine kinase inhibitor, for the treatment of metastatic RET fusion-positive non-small-cell lung cancer (NSCLC). Summary. RET fusion-positive NSCLC is a rare cancer caused by chromosomal rearrangements that lead to fusions of the RET gene with other genes, such as KIF5B and CCDC6. Until recently, patients were treated with platinum-based chemotherapy or multitargeted tyrosine kinase inhibitors. However, because of their nonspecific mechanism of action, these drugs did not have high response rates. In September 2020, the Food and Drug Administration approved pralsetinib, the first once-daily oral tyrosine kinase inhibitor, for patients with metastatic RET fusion-positive NSCLC. Pralsetinib has been demonstrated to have response rates of 57% and 70% in patients who were previously treated with platinum chemotherapy and patients who were treatment naive, respectively. Clinicians using pralsetinib should monitor for fatigue, hepatotoxicity, hemorrhagic events, hypertension, myelosuppression, pyrexia, and respiratory infections, as these may require treatment interruption, dose reduction, or treatment discontinuation. Conclusion. Pralsetinib is a unique targeted tyrosine kinase inhibitor approved for the treatment of patients with RET fusion-positive metastatic NSCLC who may desire a once-daily regimen.