Researchers from Mass General Brigham Cancer Institute reported on Apr. 1 that the targeted therapy pralsetinib led to improved long-term outcomes for patients with advanced or metastatic non-small cell lung cancers (NSCLCs) driven by RET gene fusions. The findings, published in the Journal of Clinical Oncology, are based on a phase 1/2 clinical study with a follow-up period of 42 months involving 281 patients.
RET gene fusions are known to drive tumor growth in some NSCLCs, and targeted therapies have been developed to address this mutation. The study highlights that pralsetinib treatment resulted in durable responses and manageable safety profiles among participants.
"Before selective RET inhibitors were developed, the expected overall survival for advancedRET fusion-positive NSCLC was roughly between 4 and 11 months. Now we show that pralsetinib can extend the median survival rate to 44 months," said senior author Justin Gainor, MD, Division Chief, Solid Tumor Medical Oncology at Mass General Brigham Cancer Institute. "Our findings reinforce the importance of early biomarker testing, including testing for gene fusions, in all metastatic NSCLC patients to guide treatment."
Data from the ARROW trial showed an overall response rate of 78% for previously untreated patients, while those who had received chemotherapy had a response rate of 63%. Patients with brain metastases saw a response rate of 73%. The study also found differences based on specific RET fusion partners: those with CCDC6-RET experienced longer median duration of response (47.9 months) compared to KIF5B-RET (13.1 months).
Common side effects included anemia, hypertension and reduced neutrophil count; these led to discontinuation in about one-tenth of cases and dose reductions in just over half. Three patient deaths were attributed to treatment-related causes.
The authors concluded that pralsetinib's safety profile is manageable and noted it did not cause hypersensitivity reactions seen with other RET inhibitors after immunotherapy exposure. They indicated further research is needed into resistance mechanisms against RET inhibitors.
