Introduction: Reliable diagnostic approaches to detect ALK rearrangement are critical for selecting patients eligible for crizotinib therapy. This study aimed to compare next-generation sequencing (NGS) and Ventana immunohistochemistry (IHC) in evaluating ALK rearrangements and evaluate their impact on first-line crizotinib efficacy.
Patients and Methods: A total of 472 NSCLC patients were identified as ALK-positive by NGS and/or IHC between March 2014 and February 2020. The concordance of ALK detection, overall response rate (ORR), and progression-free survival (PFS) were analyzed for 319 patients who received front-line crizotinib.
Results: First-line crizotinib (n=319) significantly prolonged PFS in comparison with chemotherapy (n=46; 12.0 vs 6.8 months; p< 0.0001). Of the 76 crizotinib-treated patients whose ALK status was assessed by both NGS and IHC, 78.9% of the patients had concordant ALK status (NGS-positive/IHC-positive), 18.4% patients were NGS-positive but IHC-negative, and 2 patients were IHC-positive but NGS-negative. Different detection assays confer no statistical difference in ORR and PFS with first-line crizotinib. The ORR in NGS only, IHC only, and both NGS and IHC was 84.3%, 90.1%, and 88.1%, respectively, while PFS was 11.4, 13.0, and 11.0 months, respectively. The ORR in NGS-positive/IHC-positive and NGS-positive/IHC-negative patients was 85.4% and 92.8%, respectively. Compared to NGS-positive/IHC-positive patients, those with NGS-positive/IHC-negative results had a trend of shorter PFS but statistical significance was not reached (mPFS, 5.9 months vs 11.5 months, p=0.43).
Conclusion: Our results demonstrate that ALK status detected by NGS and/or IHC is reliable in identifying patients with ALK-positive NSCLC who will benefit from ALK inhibitor therapy.
Keywords: ALK status evaluation, ALK IHC, ALK inhibitor