Pralsetinib can be used as a first-line therapy in treatment-naive patients diagnosed with RET fusion-positive non-small-cell lung cancer.
Approximately 1%–2% of non-small-cell lung cancers (NSCLCs) are positive for RET proto-oncogene (RET) fusions. Pralsetinib, an oral, highly potent central nervous system (CNS) penetrant, is a selective RET inhibitor. This drug has shown clinical activity in individuals diagnosed with RET fusion-positive NSCLC, included in the phase I and II ARROW study.
This clinical trial analysis of ARROW, published in the Annals of Oncology: Official Journal of the European Society for Medical Oncology, is an open-label multi-cohort phase I/II study. A total of 281 patients diagnosed with RET fusion-positive NSCLC, were recruited in this study. Pralsetinib therapy was initiated at a phase II dose of 400 mg/daily and terminated upon the investigator’s decision, disease progression, consent withdrawal, or intolerance.
The overall response rate (ORR) was 72% and 59% in treatment-naive patients and patients who previously received platinum-based chemotherapy, respectively. The median duration of treatment response was 22.3 months for patients who previously received platinum-based chemotherapy. All the treatment-naive patients and approximately 97% of patients who previously received platinum-based chemotherapy demonstrated tumor shrinkage with a median progression-free survival of 13.0 and 16.5 months in the treatment groups, respectively. In individuals with measurable intracranial metastases, the intracranial response rate was 70%, all of whom had previously received systemic treatment. The most common treatment-related adverse events (TRAEs) of grade 3–4 in treatment-naive patients included increased blood levels of creatine phosphokinase in 9%, neutropenia in 18%, lymphopenia in 9%, and hypertension in 10% of the patients. A total of 7% of the study participants discontinued pralsetinib therapy owing to TRAEs.
This study concluded that pralsetinib treatment is well-tolerated and effective in treatment-naive patients diagnosed with advanced RET fusion-positive NSCLC.
Reference
Griesinger, F., Curigliano, G., Thomas, M., Subbiah, V., Baik, C. S., Tan, D. S. W., Lee, D. H., Misch, D., Garralda, E., Kim, D. W., van der Wekken, A. J., Gainor, J. F., Paz-Ares, L., Liu, S. V., Kalemkerian, G. P., Houvras, Y., Bowles, D. W., Mansfield, A. S., Lin, J. J., . . . Mazières, J. (2022). Safety and efficacy of pralsetinib in RET fusion-positive non-small-cell lung cancer including as first-line therapy: update from the ARROW trial. Annals of Oncology, 33(11), 1168-1178. https://doi.org/10.1016/j.annonc.2022.08.002
