OncoTargets and Therapy (Jul 2020)

Comparison of Next-Generation Sequencing and Ventana Immunohistochemistry in Detecting ALK Rearrangements and Predicting the Efficacy of First-Line Crizotinib in Patients with Advanced Non-Small Cell Lung Cancer

  • Zeng L,
  • Li Y,
  • Xu Q,
  • Jiang W,
  • Lizaso A,
  • Mao X,
  • Zhang Y,
  • Yang N,
  • Wang Z

Journal volume & issue
Vol. Volume 13
pp. 7101 – 7109

Abstract

Read online

Liang Zeng,1,2,* Yizhi Li,2,* Qinqin Xu,3,* Wenjuan Jiang,2 Analyn Lizaso,4 Xinru Mao,4 Yongchang Zhang,2 Nong Yang,2 Zhenxing Wang1 1Department of Medical Oncology, The First Affiliated Hospital of Soochow University, Suzhou 215006, People’s Republic of China; 2Department of Medical Oncology, Lung Cancer and Gastrointestinal Unit, Hunan Cancer Hospital/The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha 410013, People’s Republic of China; 3Department of Medical Oncology, Qinghai Provincial People’s Hospital, Xining, People’s Republic of China; 4Department of Medical Affairs, Burning Rock Biotech, Guangzhou, 510300, People’s Republic of China*These authors contributed equally to this workCorrespondence: Nong YangDepartment of Medical Oncology,Lung Cancer and Gastrointestinal Unit, Hunan Cancer Hospital/The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha 410013, People’s Republic of ChinaTel +86 73189762327Email [email protected] WangDepartment of Medical Oncology, The First Affiliated Hospital of Soochow University, 188 Shizi Street, Suzhou 215006, People’s Republic of ChinaTel +86 73189762327Email [email protected]: 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

Keywords