ALEX Study: Efficacy of Alectinib and Crizotinib in ALK+ NSCLC

The Blood First Assay Screening Study demonstrated the clinical use of blood-based next-generation sequencing for identifying patients with ALK-positive NSCLC for alectinib treatment. Researchers examined clinical efficacy between subpopulations in the VENTANA ALK (D5F3) CDx immunohistochemistry trial and the FoundationACT (FACT; Foundation Medical, Inc.) plasma assay to better understand the link between tissue-based and blood-based testing in the ALEX phase 3 investigation.

Both alectinib (600 mg) and crizotinib (250 mg) were given to patients with advanced ALK-positive (by immunohistochemistry) NSCLC in a 1:1 ratio. Evaluation of ALK positivity in baseline plasma samples was performed by FACT, and the positive percent agreement with immunohistochemistry was calculated. This study examined PFS, ROR, and ORR across plasma ALK-positive and plasma ALK-negative subpopulations and between ITT and biomarker-evaluable groups.

Immunohistochemistry showed that all 303 patients in the ITT population (152 on alectinib and 151 on crizotinib) had ALK-positive malignancies. Of the biomarker-evaluable group of 149 patients (76 on alectinib and 73 on crizotinib), 105 patients had plasma ALK-positive malignancies, and 44 did not. Seventy-five percent (105 of 149; 95% confidence interval: 62.5-77.7) of cases had positive results from both immunohistochemistry and FACT. Baseline parameters were even with a few notable outliers, most notably tumor burden. The median progression-free survival (PFS) for plasma ALK-positive and ALK-negative patients treated with alectinib was 22.4 months. It was not estimable, while the median PFS for patients treated with crizotinib was 12.9 months and 7.3 months, and the median duration of response was 25.9 months and was not estimable, while it was 5.6 months and 11.5 months.
Both FACT and immunohistochemistry showed reasonable concordance, demonstrating the value of both approaches in detecting ALK-positive individuals. Like the ITT sample, the plasma ALK-positive population showed improved PFS with alectinib.

Source: https://pubmed.ncbi.nlm.nih.gov/35756755/

Clinical trial: https://clinicaltrials.gov/ct2/show/NCT02075840

Noé, J., Bordogna, W., Archer, V., Smoljanovic, V., Hilton, M., Woodhouse, R., Mocci, S., & Gadgeel, S. M. (2022). 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 clinical and research reports, 3(7), 100341. https://doi.org/10.1016/j.jtocrr.2022.100341