Concordance Between Tissue Detection by Immunohistochemistry and Plasma Detection by Next-Generation Sequencing in the Randomized Phase 3 ALEX Study in Patients With Treatment-Naive Advanced -Positive NSCLC.

Introduction: The Blood First Assay Screening Trial revealed the clinical applicability of blood-based next-generation sequencing to identify patients with -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 -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 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 positive and plasma -negative subpopulations.

Results: In the ITT population (303 patients; alectinib, 152; crizotinib, 151), all patients had -positive tumors by immunohistochemistry. In the biomarker-evaluable population (149 patients; alectinib, 76; crizotinib, 73), 105 had plasma -positive and 44 had plasma -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 -positive and -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 -positive patients, separately or concurrently. Alectinib was found to have superior PFS in the plasma -positive population, as in the ITT population.