Central Nervous System Disease in Patients With RET Fusion-Positive NSCLC Treated With Selpercatinib
Yonina R Murciano-Goroff1, Christina J Falcon1, Sabrina T Lin2
1Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York.
Introduction:
Central nervous system (CNS) metastases develop in nearly half of patients with RET fusion-positive NSCLCs and cause morbidity and mortality. The selective RET inhibitor selpercatinib treats existing intracranial disease, but no studies have investigated whether early initiation of selpercatinib is associated with decreased development of CNS metastases.
Methods:
A total of 61 patients with RET fusion-positive advanced NSCLC with and without CNS metastases treated with selpercatinib on the LIBRETTO-001 trial (NCT03157128) or the LIBRETTO-201 expanded access program (NCT03906331) were identified. Cumulative incidence rates (CIRs) for CNS metastases were assessed as an event of interest; systemic progression of disease and death were considered competing risks.
Results:
The median age was 65 years, and the most common 5' fusion partners were KIF5B (67%) and CCDC6 (18%). There were 24 patients (39%) who received prior platinum chemotherapy and 20 patients (33%) who received prior multikinase inhibition. The median time on selpercatinib was 21.8 months. Furthermore, 30 patients (49%) had CNS disease at baseline and 31 patients (51%) had no baseline CNS disease. CIRs of CNS progression among patients with baseline CNS disease were 3% (95% confidence interval [CI]: 0%-10%), 10% (95% CI: 0%-22%), 17% (3%-30%), 17% (3%-30%), and 20% (5%-35%) at 6, 12, 18, 24, and 36 months, respectively. CIR for CNS progression among patients without baseline CNS disease was 0% at 6, 12, 18, 24, and 36 months (95% CI: 0%-0%).
Conclusions:
CNS progression was not observed with selpercatinib therapy in patients without baseline CNS disease. CNS progression on selpercatinib was rare in patients with baseline CNS disease. Early initiation of selpercatinib is associated with decreased rates of CNS metastasis formation and progression and may play a preventive role.
Insights
Early selpercatinib use in RET fusion-positive NSCLC patients significantly reduced central nervous system (CNS) metastasis development. No CNS progression occurred in patients without baseline CNS disease, suggesting a preventive role for this RET inhibitor.
Area of Science:
- Oncology
- Medical Science
- Pharmacology
Background:
- Central nervous system (CNS) metastases are common and severe in RET fusion-positive non-small cell lung cancer (NSCLC).
- Selpercatinib, a selective RET inhibitor, treats existing CNS disease, but its role in preventing metastasis is unknown.
Purpose of the Study:
- To investigate if early initiation of selpercatinib is associated with decreased development and progression of CNS metastases in patients with RET fusion-positive NSCLC.
Main Methods:
- Retrospective analysis of 61 patients with advanced RET fusion-positive NSCLC treated with selpercatinib.
- Cumulative incidence rates (CIRs) for CNS metastases were assessed, with systemic progression and death as competing risks.
Main Results:
- No CNS progression was observed in patients without baseline CNS disease (0% CIR at 36 months).
- For patients with baseline CNS disease, CIRs for CNS progression at 36 months were 20% (95% CI: 5%-35%).
- Median follow-up was 21.8 months, with 49% having baseline CNS disease.
Conclusions:
- Selpercatinib therapy was associated with no CNS progression in patients without baseline CNS disease.
- CNS progression was rare in patients with baseline CNS disease on selpercatinib.
- Early selpercatinib initiation may play a preventive role in decreasing CNS metastasis formation and progression.
