Pralsetinib: A Review in Advanced RET Fusion-Positive NSCLC

Activating mutations in the proto-oncogene RET have been identified as an oncogenic driver of non-small cell lung cancer (NSCLC) in a small subset of patients. Pralsetinib (Gavreto®) is an orally-administered, next-generation, small-molecule selective RET inhibitor that is approved for the treatment of RET fusion-positive metastatic NSCLC. In the pivotal phase I/II ARROW trial, pralsetinib demonstrated rapid and durable anti-tumour activity in patients with advanced RET fusion-positive NSCLC who were previously treated with platinum-based chemotherapy or were treatment-naïve. Pralsetinib also showed clinical activity against intracranial metastases arising from NSCLC. Pralsetinib had a manageable tolerability profile, with the most common grade 3 treatment-related adverse events being neutropenia, hypertension, anaemia and decreased white blood cell count. Currently available data indicate that pralsetinib is a promising new targeted treatment option for patients with advanced RET fusion-positive NSCLC.RET fusions are known to drive non-small cell lung cancer (NSCLC) in a small subset of patients. Non-RET-specific multikinase inhibitors have been evaluated as targeted therapy for these patients in clinical trials, with limited success. Pralsetinib (Gavreto®) is an oral drug that directly and selectively inhibits the RET tyrosine kinase activity and is recently approved for the treatment of RET-driven NSCLC. In the pivotal ARROW trial, pralsetinib as first- or subsequent-line therapy showed rapid and durable clinical activity in patients with advanced RET fusion-positive NSCLC. The drug was also active against brain metastases from NSCLC. Pralsetinib had a manageable tolerability profile. Therefore, pralsetinib is a promising new targeted therapy option for patients with advanced RET fusion-positive NSCLC.