Alectinib versus crizotinib in treatment-naïve anaplastic lymphoma kinase-positive (ALK+) non-small-cell lung cancer: CNS efficacy results from the ALEX study

ABSTRACT Purpose The phase III ALEX study (NCT02075840), of alectinib versus crizotinib in patients with treatment-naïve advanced anaplastic lymphoma kinase mutation-positive non-small-cell lung cancer (ALK+ NSCLC), met its primary endpoint (improved progression-free survival [PFS]). We present detailed central nervous system (CNS) efficacy data from ALEX. Patients and Methods 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 (baseline and every 8 weeks). Endpoints (analyzed by subgroup: patients with/without baseline CNS metastases; patients with/without prior radiotherapy): PFS, CNS objective response rate (ORR), time to CNS progression. Results 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 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 to 0.64) and without (HR, 0.51, 95% CI, 0.33 to 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 < .0001). CNS ORR was 85.7% (alectinib) versus 71.4% (crizotinib) in patients with measurable disease who received prior radiotherapy, and 78.6% versus 40.0%, respectively, in those who had not. Conclusions 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.