Concordance Between Tissue ALK Detection by Immunohistochemistry and Plasma ALK Detection by Next-Generation Sequencing in the Randomized Phase 3 ALEX Study in Patients With Treatment-Naive Advanced ALK-Positive NSCLC
Noé J, Bordogna W, Archer V, Smoljanovic V, Hilton M, Woodhouse R, Mocci S, and Gadgeel SM. Concordance Between Tissue ALK Detection by Immunohistochemistry and Plasma ALK Detection by Next-Generation Sequencing in the Randomized Phase 3 ALEX Study in Patients With Treatment-Naive Advanced ALK-Positive NSCLC. JTO Clin Res Rep 2022; 3(7):100341.
JTO Clin Res Rep
INTRODUCTION: The Blood First Assay Screening Trial revealed the clinical applicability of blood-based next-generation sequencing to identify patients with ALK-positive NSCLC for alectinib treatment. To understand the relationship between tissue-based versus blood-based testing, we retrospectively investigated concordance between VENTANA ALK (D5F3) CDx immunohistochemistry and the FoundationACT (FACT; Foundation Medicine, Inc.) plasma assay, and compared clinical efficacy between phase 3 ALEX study subpopulations.
METHODS: Patients with advanced ALK-positive (by immunohistochemistry) NSCLC were randomized 1:1 to alectinib 600 mg or crizotinib 250 mg, twice daily. Assessable baseline plasma samples were analyzed for ALK positivity by FACT; positive percent agreement with immunohistochemistry was evaluated. Progression-free survival (PFS), duration of response, and objective response rate were compared between intention-to-treat (ITT) and biomarker-evaluable populations, and plasma ALK-positive and plasma ALK-negative subpopulations.
RESULTS: In the ITT population (303 patients; alectinib, 152; crizotinib, 151), all patients had ALK-positive tumors by immunohistochemistry. In the biomarker-evaluable population (149 patients; alectinib, 76; crizotinib, 73), 105 had plasma ALK-positive and 44 had plasma ALK-negative tumors. Positive percent agreement between immunohistochemistry and FACT was 70.5% (105 of 149; 95% confidence interval: 62.5-77.7). Baseline characteristics were generally balanced, with some exceptions, notably tumor burden. Median PFS in plasma ALK-positive and ALK-negative patients was 22.4 months and not estimable with alectinib and 7.3 months and 12.9 months with crizotinib, respectively; median duration of response was 25.9 months and not estimable with alectinib and 5.6 months and 11.5 months with crizotinib, respectively.
CONCLUSIONS: Reasonable concordance between FACT and immunohistochemistry was observed; both methods are valuable in identifying ALK-positive patients, separately or concurrently. Alectinib was found to have superior PFS in the plasma ALK-positive population, as in the ITT population.