In some non-small cell lung cancers (NSCLC), RET gene (also known as) RET fusion) can promote tumor growth. Researchers at Massachusetts General Brigham Cancer Institute evaluated the long-term efficacy and safety of pralsetinib, an FDA-approved drug that targets RET, in a phase 1/2 clinical study with 42 months of follow-up. The researchers found that the treatment produced durable responses with a manageable safety profile in 281 patients with advanced or metastatic RET fusion-positive NSCLC. Results are posted below Journal of Clinical Oncology.
“Prior to the development of selective RET inhibitors, the expected overall survival of patients with advanced disease was RET Fusion-positive NSCLC was approximately 4 to 11 months old. Here, we show that pralsetinib can extend median survival to 44 months,” said lead author Justin Gaynor, M.D., chief of solid tumor medical oncology at Massachusetts General Brigham Cancer Institute. “Our findings support the importance of early biomarker testing, including gene fusion testing, in all patients with metastatic NSCLC to guide treatment.”
The current study used data from the ARROW study, an open-label, multicenter, phase 1/2 clinical trial that enrolled 281 patients with advanced disease. RET Fusion-positive NSCLC – and additional 42-month follow-up data. The results demonstrated that the overall response rate to pralsetinib was 78% in patients without prior treatment, 63% in patients who had received chemotherapy, and 73% in patients with brain metastases.
patient RET fusion gene partner CCDC6 and KIF5B Overall response rates to treatment were high. Median duration of response was longer in patients with the following symptoms: CCDC6-RET (47.9 months) KIF5B coat (13.1 months). Common treatment-related side effects included anemia, hypertension, and decreased neutrophil counts, leading to treatment discontinuation in 10% of patients and dose reduction in 51%. Three patients died of treatment-related causes.
The authors note that pralsetinib’s safety profile was manageable, and the drug did not cause hypersensitivity (an effect sometimes induced by other RET inhibitors) in patients who had received previous immunotherapy. Further studies are needed to understand the mechanisms of resistance to RET inhibitors.
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Reference magazines:
Besse B and others. “Final efficacy and safety data from the Phase 1/2 ARROW study of pralsetinib in patients with advanced RET fusion-positive non-small cell lung cancer (NSCLC)” JCO DOI: 10.1200/JCO-25-01489
