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Alectinib's activity against CNS metastases from ALK-positive non-small cell lung cancer: a single institution case
Giulio Metro1, Gianluigi Lunardi2, Chiara Bennati3
1Medical Oncology, Santa Maria della Misericordia Hospital, Azienda Ospedaliera di Perugia, via Dottori, 1, 06156, Perugia, Italy. giulio.metro@yahoo.com.
Abstract:
In the present study we assessed the activity of the next-generation anaplastic lymphoma kinase (ALK)-tyrosine kinase inhibitor (-TKI) alectinib, in patients with ALK-postive, advanced non-small cell lung cancer (NSCLC) and central nervous system (CNS) metastases. NSCLCs with ALK-positive disease, as assessed by fluorescence in situ hybridization, and CNS metastases were treated with alectinib 600 mg BID. Included patients were followed prospectively in order to evaluate the efficacy of the drug, with particular emphasis on activity in the CNS. Eleven consecutive patients were enrolled. The majority of them were pretreated with crizotinib (n = 10, 90.9 %), and cranial radiotherapy (n = 8, 72.7 %). Six of the seven patients with measurable CNS disease experienced a CNS response, including three patients who were naïve for cranial radiation. Median duration of response was 8 months. For the whole population, median CNS-progression-free survival (-PFS), systemic-PFS, overall-PFS, overall survival, and 1-year survival were 8, 11, 8, 13 months, and 31.1 %, respectively. Two patients experiencing a CNS response were assessed for alectinib's concentrations in serum and cerebro-spinal fluid (CSF), and showed a CSF-to-serum ratio ranging from 0.001 to 0.003 ng/mL. Alectinib is highly active against CNS metastases from ALK-positive NSCLCs, irrespective of prior treatment(s) with ALK-TKI(s) and/or cranial radiotherapy. The low CSF-to-serum ratio of alectinib suggests that measuring the concentrations of the drug in the CSF may not be a reliable surrogate of its distribution into the CNS.
Insights
Alectinib shows high efficacy in treating brain metastases for advanced ALK-positive non-small cell lung cancer (NSCLC). This next-generation anaplastic lymphoma kinase (ALK)-tyrosine kinase inhibitor (TKI) offers significant CNS response, even after prior treatments.
Area of Science:
- Oncology
- Pharmacology
- Neurology
Background:
- Advanced non-small cell lung cancer (NSCLC) frequently develops central nervous system (CNS) metastases.
- Anaplastic lymphoma kinase (ALK) rearrangements are key drivers in a subset of NSCLC patients.
- CNS metastases in ALK-positive NSCLC pose a significant therapeutic challenge, often requiring specialized treatment strategies.
Purpose of the Study:
- To evaluate the efficacy of alectinib, a next-generation ALK-tyrosine kinase inhibitor (TKI), in patients with ALK-positive advanced NSCLC and CNS metastases.
- To assess the activity of alectinib specifically within the CNS, including its impact on progression-free survival.
- To investigate the relationship between alectinib concentrations in serum and cerebrospinal fluid (CSF).
Main Methods:
- Prospective evaluation of eleven consecutive patients with ALK-positive advanced NSCLC and CNS metastases treated with alectinib 600 mg BID.
- Assessment of efficacy with a focus on CNS activity, including response rates and duration of response.
- Measurement of alectinib concentrations in serum and CSF in a subset of patients to determine CSF-to-serum ratio.
Main Results:
- Six of seven patients with measurable CNS disease achieved a CNS response, including three radiation-naïve patients.
- Median duration of CNS response was 8 months.
- Median CNS-progression-free survival (PFS) was 8 months, with overall PFS of 8 months and overall survival of 13 months.
- A low CSF-to-serum ratio (0.001-0.003 ng/mL) was observed for alectinib.
Conclusions:
- Alectinib demonstrates high activity against CNS metastases in ALK-positive NSCLC, regardless of prior ALK-TKI or cranial radiotherapy.
- Alectinib offers a promising therapeutic option for patients with brain metastases from ALK-positive NSCLC.
- The low CSF-to-serum ratio suggests that CSF drug concentrations may not reliably reflect CNS distribution.
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