KEY TAKEAWAYS
- Patients with RET fusion-positive NSCLC were examined for the efficacy of selpercatinib in phase 2 LIBRETTO-201 EAP trial.
- Patients either had CNS metastases at baseline or none.
- Selpercatinib was related to lower CNS metastases development rates in those without CNS illness at baseline.
- Early administration of selpercatinib is associated with reduced progression rates of CNS metastases.
In RET fusion-positive non-small cell lung cancers (NSCLCs) patients, the development of central nervous system (CNS) metastases accounted for morbidity and mortality in 50% patients. While, the selected intracranial disease can be treated with the selective RET inhibitor selpercatinib, no study has yet determined whether the early stage of selpercatinib is associated with decreased CNS metastases development.
A total of 61 patients were identified who had received selpercatinib as part of either the LIBRETTO-001 trial (NCT03157128) or the LIBRETTO-201 expanded access programs (EAP, NCT03906331) for RET fusion-positive advanced NSCLC with or without CNS metastases. There was an evaluation of the cumulative incidence rates (CIRs) for central nervous system metastases as the event of interest, with systemic disease progression and mortality as competing risks.
KIF5B (67%) and CCDC6 (18%) were the most prevalent 5′ fusion partners, and the median age was 65. About 24 patients (39%) had previously undergone platinum chemotherapy, while 20 patients (33%) had once received multikinase inhibition. Treatment with selpercatinib was continued for a median of 21.8 months. About 30 (49%) of patients had CNS illness at baseline, while 31 (51%) did not. Among patients who already had CNS illness at baseline, the CIRs of progression was 3% (95% CI: 0-10%) at 6 months, 10% (95% CI: 0-22%) at 12 months, 17% (3-30%) at 18 months, 20% (5-35%) at 24 months, and 20% (5-35%) at 36 months. Patients without CNS illness at baseline had 0% CNS progression CIRs at 6, 12, 18, 24, and 36 months (95% CI: 0%-0%).
In patients without preexisting CNS disease, selpercatinib medication did not cause CNS progression. In patients who already had CNS illness, selpercatinib-induced progression was highly uncommon. Selpercatinib may be preventative, as it is linked to lower rates of CNS metastases formation and progression.
Source: https://linkinghub.elsevier.com/retrieve/pii/S1556-0864(23)00008-4
Clinical Trial: https://clinicaltrials.gov/ct2/show/NCT03157128
Murciano-Goroff YR, Falcon CJ, Lin ST, Chacko C, Grimaldi G, Liu D, Wilhelm C, Iasonos A, Drilon A. Original article: Central nervous system disease in patients with RET fusion-positive non-small cell lung cancer treated with selpercatinib. J Thorac Oncol. 2023 Jan 16:S1556-0864(23)00008-4. doi: 10.1016/j.jtho.2023.01.008. Epub ahead of print. PMID: 36657661.
