Alectinib's activity against CNS metastases from ALK-positive non-small cell lung cancer: a single institution case series.
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.
Medical Oncology, Santa Maria della Misericordia Hospital, Azienda Ospedaliera di Perugia, via Dottori, 1, 06156, Perugia, Italy. giulio.metro@yahoo.com.
Giulio
G
Metro
Medical Oncology, Sacro Cuore-Don Calabria Hospital, Negrar, VR, Italy.
Gianluigi
G
Lunardi
Medical Oncology, Santa Maria della Misericordia Hospital, Azienda Ospedaliera di Perugia, via Dottori, 1, 06156, Perugia, Italy.
Chiara
C
Bennati
Neuroradiology, Santa Maria della Misericordia Hospital, Azienda Ospedaliera di Perugia, Perugia, Italy.
Pietro
P
Chiarini
Biostatistics & Data Management Core, Regina Elena Cancer Institute, Rome, Italy.
Isabella
I
Sperduti
Medical Oncology, Santa Maria della Misericordia Hospital, Azienda Ospedaliera di Perugia, via Dottori, 1, 06156, Perugia, Italy.
Biagio
B
Ricciuti
Medical Oncology, Santa Maria della Misericordia Hospital, Azienda Ospedaliera di Perugia, via Dottori, 1, 06156, Perugia, Italy.
Luca
L
Marcomigni
Clinica Neurologica, Department of Medicine, Santa Maria della Misericordia Hospital, University of Perugia, Perugia, Italy.
Cinzia
C
Costa
Medical Oncology, Santa Maria della Misericordia Hospital, Azienda Ospedaliera di Perugia, via Dottori, 1, 06156, Perugia, Italy.
Lucio
L
Crinò
Neuroradiology, Santa Maria della Misericordia Hospital, Azienda Ospedaliera di Perugia, Perugia, Italy.
Piero
P
Floridi
Medical Oncology, Sacro Cuore-Don Calabria Hospital, Negrar, VR, Italy.
Stefania
S
Gori
Medical Oncology, Santa Maria della Misericordia Hospital, Azienda Ospedaliera di Perugia, via Dottori, 1, 06156, Perugia, Italy.
Rita
R
Chiari
D000328:Adult; D000368:Aged; D000077548:Anaplastic Lymphoma Kinase; D001921:Brain / Q000000981:diagnostic imaging; D002227:Carbazoles / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000000981:diagnostic imaging / Q000473:pathology*; D016543:Central Nervous System Neoplasms / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000556:secondary*; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000000981:diagnostic imaging / Q000473:pathology*; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D010880:Piperidines / Q000627:therapeutic use*; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D020794:Receptor Protein-Tyrosine Kinases / Q000097:blood / Q000134:cerebrospinal fluid; D012189:Retrospective Studies
D002227:Carbazoles; D010880:Piperidines; D047428:Protein Kinase Inhibitors; C000626173:ALK protein, human; D000077548:Anaplastic Lymphoma Kinase; D020794:Receptor Protein-Tyrosine Kinases; C582670:alectinib
ALK; Alectinib; CNS metastases; Cerebro-spinal fluid; Non-small cell lung cancer