The final analysis of the pivotal phase I/II LIBRETTO-001 trial has reinforced the therapeutic potential of selpercatinib in RET fusion-positive non-small cell lung cancer (NSCLC), with extended follow-up data showing sustained clinical benefit across patient populations.
The comprehensive analysis, representing an additional 19 months of follow-up since the primary analysis that led to the drug's approval, included 316 patients - 247 who had received prior platinum-based chemotherapy and 69 treatment-naive individuals. Patients received selpercatinib in 28-day continuous cycles, with doses ranging from 20 mg once daily to 240 mg twice daily during dose escalation, before settling at the recommended phase II dose of 160 mg twice daily.
Robust Efficacy Across Patient Groups
The trial demonstrated compelling efficacy metrics across both treatment-experienced and naive populations. In pretreated patients, the objective response rate reached 62%, with a median duration of response extending to 31.6 months. Treatment-naive patients showed even more impressive results, achieving an 83% response rate with a median response duration of 20.3 months.
Survival outcomes were particularly noteworthy. Pretreated patients achieved a median progression-free survival of 26.2 months and a median overall survival of 47.6 months. Treatment-naive patients demonstrated a median progression-free survival of 22.0 months, while median overall survival had not yet been reached. The 3-year landmark analysis revealed that 57% of pretreated and 66% of treatment-naive patients were still alive.
Significant Impact on Brain Metastases
One of the most striking findings emerged from the subset of 26 patients with measurable central nervous system (CNS) metastases at baseline. In this historically challenging-to-treat population, selpercatinib achieved an impressive 85% CNS objective response rate. The median CNS response duration was 9.4 months, with a median CNS progression-free survival of 11.0 months.
Safety and Clinical Implications
Throughout the extended follow-up period, selpercatinib maintained its established safety profile, consistent with previous reports. These results further solidify the drug's position as a valuable therapeutic option for RET fusion-positive NSCLC patients.
Dr. Alexander Drilon of Memorial Sloan Kettering Cancer Center and Weill Cornell Medical Center, the study's corresponding author, and colleagues concluded that selpercatinib continues to demonstrate durable responses and significant intracranial activity, while maintaining a manageable safety profile in this patient population.
