Outcomes According to ALK Status Determined by Central IHC or FISH in Patients with ALK-Positive NSCLC Enrolled in the Phase III ALEX Study

Tony Mok; Solange Peters; D Ross Camidge; Johannes Noé; Shirish Gadgeel; Sai-Hong Ignatius Ou; Dong-Wan Kim; Krzysztof Konopa; Emanuela Pozzi; Ting Liu; Isabell R Loftin; Crystal Williams; Alice T Shaw

doi:10.1016/j.jtho.2020.10.007

Outcomes According to ALK Status Determined by Central IHC or FISH in Patients with ALK-Positive NSCLC Enrolled in the Phase III ALEX Study

J Thorac Oncol. 2020 Oct 24:S1556-0864(20)30815-7. doi: 10.1016/j.jtho.2020.10.007. Online ahead of print.

Authors

Tony Mok¹, Solange Peters², D Ross Camidge³, Johannes Noé⁴, Shirish Gadgeel⁵, Sai-Hong Ignatius Ou⁶, Dong-Wan Kim⁷, Krzysztof Konopa⁸, Emanuela Pozzi⁴, Ting Liu⁴, Isabell R Loftin⁹, Crystal Williams⁹, Alice T Shaw¹⁰

Affiliations

¹ State Key Laboratory of Translational Oncology, Chinese University of Hong Kong, Hong Kong. Electronic address: tony@clo.cuhk.edu.hk.
² Lausanne University Hospital, Lausanne, Switzerland.
³ University of Colorado, Denver, Colorado.
⁴ F. Hoffmann-La Roche Ltd, Basel, Switzerland.
⁵ Department of Internal Medicine, Division of Hematology and Oncology, University of Michigan, Ann Arbor, Michigan.
⁶ University of California, Irvine School of Medicine, Orange, California.
⁷ Seoul National University Hospital, Seoul, South Korea.
⁸ Department of Oncology and Radiotherapy, Medical University of Gdansk, Gdansk, Poland.
⁹ Ventana Medical Systems Inc, Tucson, Arizona.
¹⁰ Massachusetts General Hospital, Boston, Massachusetts.

PMID: 34756882
DOI: 10.1016/j.jtho.2020.10.007

Abstract

Introduction: We retrospectively examined progression-free survival (PFS) and response by ALK fluorescence in-situ hybridization (FISH) status in patients with advanced ALK immunohistochemistry (IHC)-positive non-small-cell lung cancer (NSCLC) in the ALEX study.

Methods: 303 treatment-naïve patients were randomized to receive twice-daily alectinib 600 mg or crizotinib 250 mg. ALK status was assessed centrally using Ventana ALK (D5F3) CDx IHC and Vysis ALK Break Apart FISH Probe Kit. Primary endpoint: investigator-assessed PFS. Secondary endpoints of interest: objective response rate (ORR) and duration.

Results: Investigator-assessed PFS was significantly prolonged with alectinib versus crizotinib in ALK IHC-positive/FISH-positive tumors (n = 203, 67%) (HR 0.37, 95% CI: 0.25-0.56) and ALK IHC-positive/FISH-uninformative tumors (n = 61, 20%) (HR 0.39, 95% CI: 0.20-0.78), but not ALK IHC-positive/FISH-negative tumors (n = 39, 13%) (HR 1.33, 95% CI: 0.6-3.2). ORRs were higher with alectinib versus crizotinib in ALK IHC-positive/FISH-positive tumors 90.6% versus 81.4%; stratified odds ratio [OR] 2.22, 95% CI: 0.97-5.07) and ALK IHC-positive/FISH-uninformative tumors (96.0% versus 75.0%; OR 9.29, 95% CI: 1.05-81.88), but not ALK IHC-positive/FISH-negative tumors (28.6% versus 44.4%; OR 0.45, 95% CI: 0.12-1.74). Next-generation sequencing (NGS) was performed in 35/39 patients with ALK IHC-positive/FISH-negative tumors; no ALK fusion was identified in 20/35 (57.1%) patients by NGS, but 10/20 (50.0%) had partial response/stable disease.

Conclusion: Outcomes of patients with ALK IHC-positive/FISH-positive and ALK IHC-positive/FISH-uninformative NSCLC were similar to the overall ALEX population. These results suggest that Ventana ALK IHC is a standard testing method for selecting patients for treatment with alectinib.

Keywords: ALK-positive; Alectinib; FISH; IHC; NSCLC.