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 (R)) 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-naive. 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. Plain Language Summary 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 (R)) 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.