KEY TAKEAWAYS
- Effectiveness in selective RET inhibitor selpercatinib to treat existing intracranial disease in patients with RET fusion-positive advanced NSCLC in the LIBRETTO-001 trial (NCT03157128) or the LIBRETTO-201 expanded access program (NCT03906331)
- Nearly 1/2 of patients with RET fusion-positive NSCLCs develop central nervous system (CNS) metastases, which cause significant morbidity and mortality.
- CIRs for CNS metastases were assessed as an event of interest, and systemic disease progression and death were considered competing risks.
- CNS progression was not observed with selpercatinib therapy in patients without baseline CNS disease. Rare in patients with baseline CNS disease.
- Early initiation of selpercatinib is associated with decreased rates of CNS metastasis formation and progression, indicating its potential role in prevention.
About 1/2 of patients with RET fusion-positive NSCLCs will develop CNS metastases, which are a leading cause of morbidity and mortality. While selpercatinib, a selective RET inhibitor, is effective in treating established intracranial disease, it is unknown whether or whether earlier administration of the drug is linked to a lower risk of CNS metastases.
About 61 patients were identified who had received selpercatinib as part of either the LIBRETTO-001 trial (NCT03157128) or the LIBRETTO-201 extended access programme (NCT03906331) for RET fusion-positive advanced NSCLC with or without CNS metastases. The CNS metastases CIR was evaluated as the endpoint, with systemic disease progression and mortality as competing hazards.
KIF5B (67%) and CCDC6 (18%) were the most prevalent 5′ fusion partners, and the median age was 65. Twenty-four patients (39%) had previously undergone platinum-based chemotherapy, while 20 (33% had once received multikinase inhibition). The average duration of treatment with selpercatinib was 21 months and 18 days. Moreover, at baseline, CNS illness was present in 30 individuals (49%) and absent in 31 patients (51%). At 6, 12, 18, 24, and 36 months, CNS progression CIRs were 3% (95% CI: 0%-10%), 10% (95% CI: 0%-22%), 17% (CI: 3%-30%), and 20% (CI: 5%-35%) among patients with baseline CNS illness.
In 6, 12, 18, 24, and 36 months, the CIR for CNS progression in patients without baseline CNS illness was 0% (95% CI, 0%). In individuals without preexisting CNS disease, selpercatinib treatment did not result in any CNS progression. Selpercatinib-induced CNS progression was uncommon in patients with preexisting CNS illness. Selpercatinib may be a preventative measure against the development and spread of Brain metastases if it is started early.
Source: https://pubmed.ncbi.nlm.nih.gov/36657661/
Clinical trial: https://clinicaltrials.gov/ct2/show/NCT03157128
Murciano-Goroff, Y.R., Falcon, C.J., Lin, S.T., Chacko, C., Grimaldi, G., Liu, D., Wilhelm, C., Iasonos, A. and Drilon, A. (2023). Central Nervous System Disease in Patients With RET Fusion-Positive NSCLC Treated With Selpercatinib. Journal of Thoracic Oncology. doi:https://doi.org/10.1016/j.jtho.2023.01.008.
