Outcomes According to ALK Status Determined by Central IHC or FISH in Patients with ALK-Positive NSCLC Enrolled in the Phase III ALEX Study

ABSTRACT Introduction We retrospectively examined progression-free survival (PFS) and response by ALK fluorescence in-situ hybridization (FISH) status in patients with advanced ALK immunohistochemistry (IHC)-positive non-small-cell lung cancer (NSCLC) in the ALEX study. Methods 303 treatment-naive patients were randomized to receive twice-daily alectinib 600 mg or crizotinib 250 mg. ALK status was assessed centrally using Ventana ALK (D5F3) CDx IHC and Vysis ALK Break Apart FISH Probe Kit. Primary endpoint: investigator-assessed PFS. Secondary endpoints of interest: objective response rate (ORR) and duration. Results Investigator-assessed PFS was significantly prolonged with alectinib versus crizotinib in ALK IHC-positive/FISH-positive tumors (n = 203, 67%) (HR 0.37, 95% CI: 0.25–0.56) and ALK IHC-positive/FISH-uninformative tumors (n = 61, 20%) (HR 0.39, 95% CI: 0.20–0.78), but not ALK IHC-positive/FISH-negative tumors (n = 39, 13%) (HR 1.33, 95% CI: 0.6–3.2). ORRs were higher with alectinib versus crizotinib in ALK IHC-positive/FISH-positive tumors 90.6% versus 81.4%; stratified odds ratio [OR] 2.22, 95% CI: 0.97–5.07) and ALK IHC-positive/FISH-uninformative tumors (96.0% versus 75.0%; OR 9.29, 95% CI: 1.05–81.88), but not ALK IHC-positive/FISH-negative tumors (28.6% versus 44.4%; OR 0.45, 95% CI: 0.12–1.74). Next-generation sequencing (NGS) was performed in 35/39 patients with ALK IHC-positive/FISH-negative tumors; no ALK fusion was identified in 20/35 (57.1%) patients by NGS, but 10/20 (50.0%) had partial response/stable disease. Conclusion Outcomes of patients with ALK IHC-positive/FISH-positive and ALK IHC-positive/FISH-uninformative NSCLC were similar to the overall ALEX population. These results suggest that Ventana ALK IHC is a standard testing method for selecting patients for treatment with alectinib.