1. Alectinib versus crizotinib in treatment-naive anaplastic lymphoma kinase-positive (ALK+) non-small-cell lung cancer: CNS efficacy results from the ALEX study
- Author
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Alice T. Shaw, Shirish M. Gadgeel, Solange Peters, S-H.I. Ou, Silvia Novello, Ali Zeaiter, Maurice Pérol, Anna Wrona, D.R. Camidge, Dong Wan Kim, Bogdana Balas, Eveline Nüesch, Ting Liu, Tony Mok, and Rafael Rosell
- Subjects
0301 basic medicine ,Alectinib ,Oncology ,Male ,Adult ,Aged ,Aged, 80 and over ,Anaplastic Lymphoma Kinase/antagonists & inhibitors ,Anaplastic Lymphoma Kinase/genetics ,Brain/diagnostic imaging ,Brain/drug effects ,Brain/radiation effects ,Brain Neoplasms/diagnostic imaging ,Brain Neoplasms/genetics ,Brain Neoplasms/secondary ,Brain Neoplasms/therapy ,Carbazoles/pharmacology ,Carbazoles/therapeutic use ,Carcinoma, Non-Small-Cell Lung/diagnostic imaging ,Carcinoma, Non-Small-Cell Lung/genetics ,Carcinoma, Non-Small-Cell Lung/secondary ,Carcinoma, Non-Small-Cell Lung/therapy ,Chemoradiotherapy/methods ,Crizotinib/pharmacology ,Crizotinib/therapeutic use ,Disease Progression ,Female ,Humans ,Lung/diagnostic imaging ,Lung/drug effects ,Lung/radiation effects ,Lung Neoplasms/diagnostic imaging ,Lung Neoplasms/genetics ,Lung Neoplasms/pathology ,Lung Neoplasms/therapy ,Magnetic Resonance Imaging ,Middle Aged ,Piperidines/pharmacology ,Piperidines/therapeutic use ,Treatment Outcome ,Tumor Burden/drug effects ,Tumor Burden/radiation effects ,Young Adult ,Lung Neoplasms ,ALK+ ,medicine.medical_treatment ,0302 clinical medicine ,Piperidines ,Carcinoma, Non-Small-Cell Lung ,Clinical endpoint ,Anaplastic lymphoma kinase ,Anaplastic Lymphoma Kinase ,Lung ,Brain Neoplasms ,Hazard ratio ,Brain ,Hematology ,Chemoradiotherapy ,Tumor Burden ,030220 oncology & carcinogenesis ,CNS ,medicine.drug ,medicine.medical_specialty ,Carbazoles ,03 medical and health sciences ,Crizotinib ,Internal medicine ,medicine ,Carcinoma ,Lung cancer ,non-small-cell lung cancer ,business.industry ,medicine.disease ,Radiation therapy ,030104 developmental biology ,business - Abstract
The phase III ALEX study in patients with treatment-naive advanced anaplastic lymphoma kinase mutation-positive (ALK+) non-small-cell lung cancer (NSCLC) met its primary end point of improved progression-free survival (PFS) with alectinib versus crizotinib. Here, we present detailed central nervous system (CNS) efficacy data from ALEX. Overall, 303 patients aged ≥18 years underwent 1:1 randomization to receive twice-daily doses of alectinib 600 mg or crizotinib 250 mg. Brain imaging was conducted in all patients at baseline and every subsequent 8 weeks. End points (analyzed by subgroup: patients with/without baseline CNS metastases; patients with/without prior radiotherapy) included PFS, CNS objective response rate (ORR), and time to CNS progression. In total, 122 patients had Independent Review Committee-assessed baseline CNS metastases (alectinib, n = 64; crizotinib, n = 58), 43 had measurable lesions (alectinib, n = 21; crizotinib, n = 22), and 46 had received prior radiotherapy (alectinib, n = 25; crizotinib, n = 21). Investigator-assessed PFS with alectinib was consistent between patients with baseline CNS metastases [hazard ratio (HR) 0.40, 95% confidence interval (CI): 0.25-0.64] and those without (HR 0.51, 95% CI: 0.33-0.80, P interaction = 0.36). Similar results were seen in patients regardless of prior radiotherapy. Time to CNS progression was significantly longer with alectinib versus crizotinib and comparable between patients with and without baseline CNS metastases (P < 0.0001). CNS ORR was 85.7% with alectinib versus 71.4% with crizotinib in patients who received prior radiotherapy and 78.6% versus 40.0%, respectively, in those who had not. Alectinib demonstrated superior CNS activity and significantly delayed CNS progression versus crizotinib in patients with previously untreated, advanced ALK+ NSCLC, irrespective of prior CNS disease or radiotherapy. ClinicalTrials.gov NCT02075840.
- Published
- 2018