Pralsetinib: A Review in Advanced RET Fusion-Positive NSCLC

Drugs. 2022 May;82(7):811-816. doi: 10.1007/s40265-022-01720-4. Epub 2022 May 19.

Abstract

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.

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®) 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.

Publication types

  • Review

MeSH terms

  • Carcinoma, Non-Small-Cell Lung* / drug therapy
  • Carcinoma, Non-Small-Cell Lung* / genetics
  • Humans
  • Lung Neoplasms* / drug therapy
  • Lung Neoplasms* / genetics
  • Proto-Oncogene Proteins c-ret / genetics
  • Pyrazoles / therapeutic use
  • Pyridines
  • Pyrimidines

Substances

  • Pyrazoles
  • Pyridines
  • Pyrimidines
  • pralsetinib
  • Proto-Oncogene Proteins c-ret
  • RET protein, human