Researchers have 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.
303 treatment-naïve patients were randomized to receive twice-daily Alectinib ( Alecensa ) 600 mg or Crizotinib ( Xalkori ) 250 mg.
ALK status was assessed centrally using Ventana ALK (D5F3) CDx IHC and Vysis ALK Break Apart FISH Probe Kit.
The primary endpoint was investigator-assessed progression-free survival. Secondary endpoints of interest were: objective response rate ( ORR ) and duration ( DoR ).
Investigator-assessed progression-free survival was significantly prolonged with Alectinib versus Crizotinib in ALK IHC-positive / FISH-positive tumors ( n = 203, 67% ) ( hazard ratio, 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 ).
The objective response rates 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.
In conclusion, outcomes of patients with ALK IHC-positive / FISH-positive and ALK IHC-positive / FISH-uninformative non-small-cell lung cancer 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. ( Xagena )
Mok T et al, J Thorac Oncol 2020; Online ahead of print