PMID- 33334571
OWN - NLM
STAT- MEDLINE
DCOM- 20210421
LR  - 20220707
IS  - 1556-1380 (Electronic)
IS  - 1556-0864 (Linking)
VI  - 16
IP  - 2
DP  - 2021 Feb
TI  - Outcomes According to ALK Status Determined by Central Immunohistochemistry or 
      Fluorescence In Situ Hybridization in Patients With ALK-Positive NSCLC Enrolled 
      in the Phase 3 ALEX Study.
PG  - 259-268
LID - S1556-0864(20)30815-7 [pii]
LID - 10.1016/j.jtho.2020.10.007 [doi]
AB  - 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 NSCLC in the ALEX study. 
      METHODS: A total of 303 treatment-naive 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 end point is investigator-assessed PFS. Secondary end points of 
      interest are objective response rate and duration. RESULTS: Investigator-assessed 
      PFS was significantly prolonged with alectinib versus crizotinib in ALK 
      IHC-positive and FISH-positive tumors (n = 203, 67%) (hazard ratio [HR] = 0.37, 
      95% confidence interval [CI]: 0.25-0.56; p < 0.0001) and ALK IHC-positive and 
      FISH-uninformative tumors (n = 61, 20%) (HR = 0.39, 95% CI: 0.20-0.78) but not in 
      ALK IHC-positive and FISH-negative tumors (n = 39, 13%) (HR = 1.33, 95% CI: 
      0.6-3.2). Objective response rates were higher with alectinib versus crizotinib 
      in ALK IHC-positive and FISH-positive tumors (90.6% versus 81.4%; stratified OR = 
      2.22, 95% CI: 0.97-5.07) and ALK IHC-positive and FISH-uninformative tumors 
      (96.0% versus 75.0%; OR = 9.29, 95% CI: 1.05-81.88) but not in ALK IHC-positive 
      and FISH-negative tumors (28.6% versus 44.4%; OR = 0.45, 95% CI: 0.12-1.74). 
      Next-generation sequencing was performed in 35 of 39 patients with ALK 
      IHC-positive and FISH-negative tumors; no ALK fusion was identified in 20 of 35 
      patients (57.1%) by next-generation sequencing, but 10 of 20 (50.0%) had partial 
      response or stable disease. CONCLUSIONS: Outcomes of patients with ALK 
      IHC-positive and FISH-positive and ALK IHC-positive and FISH-uninformative NSCLC 
      were similar to those of the overall ALEX population. These results suggest that 
      Ventana ALK IHC is a standard testing method for selecting patients for treatment 
      with alectinib.
CI  - Copyright (c) 2020 International Association for the Study of Lung Cancer. 
      Published by Elsevier Inc. All rights reserved.
FAU - Mok, Tony
AU  - Mok T
AD  - State Key Laboratory of Translational Oncology, Chinese University of Hong Kong, 
      Hong Kong. Electronic address: tony@clo.cuhk.edu.hk.
FAU - Peters, Solange
AU  - Peters S
AD  - Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne University Hospital, 
      Lausanne, Switzerland.
FAU - Camidge, D Ross
AU  - Camidge DR
AD  - Division of Medical Oncology, University of Colorado, Denver, Colorado.
FAU - Noe, Johannes
AU  - Noe J
AD  - F. Hoffmann-La Roche Ltd., Basel, Switzerland.
FAU - Gadgeel, Shirish
AU  - Gadgeel S
AD  - Division of Hematology and Oncology, Department of Internal Medicine, University 
      of Michigan, Ann Arbor, Michigan; Department of Internal Medicine, Henry Ford 
      Cancer Institute, Henry Ford Health System, Detroit, Michigan.
FAU - Ou, Sai-Hong Ignatius
AU  - Ou SI
AD  - Chao Family Comprehensive Cancer Center, University of California, Irvine, 
      California.
FAU - Kim, Dong-Wan
AU  - Kim DW
AD  - Seoul National University Hospital, Seoul, South Korea.
FAU - Konopa, Krzysztof
AU  - Konopa K
AD  - Department of Oncology and Radiotherapy, Medical University of Gdansk, Gdansk, 
      Poland.
FAU - Pozzi, Emanuela
AU  - Pozzi E
AD  - F. Hoffmann-La Roche Ltd., Basel, Switzerland.
FAU - Liu, Ting
AU  - Liu T
AD  - F. Hoffmann-La Roche Ltd., Basel, Switzerland.
FAU - Loftin, Isabell R
AU  - Loftin IR
AD  - Ventana Medical Systems Inc., Tucson, Arizona.
FAU - Williams, Crystal
AU  - Williams C
AD  - Ventana Medical Systems Inc., Tucson, Arizona.
FAU - Shaw, Alice T
AU  - Shaw AT
AD  - Massachusetts General Hospital Cancer Center and Department of Medicine, 
      Massachusetts General Hospital, Boston, Massachusetts; Novartis Institutes for 
      BioMedical Research, Cambridge, Massachusetts.
LA  - eng
PT  - Clinical Trial, Phase III
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20201024
PL  - United States
TA  - J Thorac Oncol
JT  - Journal of thoracic oncology : official publication of the International 
      Association for the Study of Lung Cancer
JID - 101274235
RN  - EC 2.7.10.1 (Anaplastic Lymphoma Kinase)
SB  - IM
CIN - J Thorac Oncol. 2022 Jun;17(6):e61-e62. PMID: 35623681
CIN - J Thorac Oncol. 2022 Jun;17(6):e62-e63. PMID: 35623682
MH  - Anaplastic Lymphoma Kinase/genetics
MH  - Humans
MH  - Immunohistochemistry
MH  - In Situ Hybridization, Fluorescence
MH  - *Lung Neoplasms/drug therapy/genetics
MH  - Retrospective Studies
OTO - NOTNLM
OT  - ALK-positive
OT  - Alectinib
OT  - FISH
OT  - IHC
OT  - NSCLC
EDAT- 2020/12/19 06:00
MHDA- 2021/04/22 06:00
CRDT- 2020/12/18 05:32
PHST- 2020/04/28 00:00 [received]
PHST- 2020/09/18 00:00 [revised]
PHST- 2020/10/04 00:00 [accepted]
PHST- 2020/12/19 06:00 [pubmed]
PHST- 2021/04/22 06:00 [medline]
PHST- 2020/12/18 05:32 [entrez]
AID - S1556-0864(20)30815-7 [pii]
AID - 10.1016/j.jtho.2020.10.007 [doi]
PST - ppublish
SO  - J Thorac Oncol. 2021 Feb;16(2):259-268. doi: 10.1016/j.jtho.2020.10.007. Epub 
      2020 Oct 24.