Dichotomous ALK-IHC Is a Better Predictor for ALK Inhibition Outcome than Traditional ALK-FISH in Advanced Non-Small Cell Lung Cancer

A. J. van der Wekken*, Rianne Pelgrim, Nils 't Hart, Naomi Werner, Mirjam Mastik, Lizza Hendriks, Erik Hfm van der Heijden, Monika Looijen-Salamon, A Joop de Langen, Jeske Staal-van den Brekel, Sietske Riemersma, Ben E van den Borne, Ernst-Jan M Speel, Anne-Marie C Dingemans, T Jeroen N Hiltermann, Anke van den Berg, Wim Timens, Ed Schuuring, H. J. M. Groen

*Corresponding author voor dit werk

OnderzoeksoutputAcademicpeer review

66 Citaten (Scopus)

Samenvatting

PURPOSE: ALK rearrangement detection using fluorescence in situ hybridization (FISH) is the standard test to identify non-small cell lung carcinoma (NSCLC) patients eligible for treatment with ALK inhibitors. Recently ALK protein expression in resectable NSCLC showed predictive value. We evaluated tumor response rate and survival after crizotinib treatment of advanced NSCLC patients with ALK activation using both dichotomous immunohistochemical staining (IHC) and FISH. Design Stage IV NSCLC patients treated with crizotinib were selected. Tumor response was assessed. ALK rearrangements were detected by FISH (Vysis ALK-Break-Apart FISH-Probe KIT) and IHC ( Ventana ALK-D5F3-CDx assay). Cohorts of ALK-FISH-positive advanced NSCLC patients from 4 other hospitals were used for validation. Results Twenty-nine consecutive patients with ALK-positive advanced NSCLC diagnosed by FISH and/or IHC on small biopsies or fine needle aspirations (FNA) were treated with ALK inhibitors. All ALK-IHC-positive patients responded to crizotinib except three with primary resistance. No tumor response was observed in 13 ALK-FISH-positive but ALK-IHC-negative patients This was confirmed in an external cohort of 16 patients. ROC curves for ALK-IHC and ALK-FISH compared to treatment outcome, showed that dichotomous ALK-IHC outperforms ALK-FISH (tumor response AUC 0.86 vs. 0.64 p=0.03; PFS AUC 0.86 vs. 0.36 p=0.005; OS AUC 0.78 vs. 0.41 p=0.01, respectively). Conclusions Dichotomous ALK-IHC is superior to ALK-FISH on small biopsies and FNA to predict tumor response and survival to crizotinib for advanced NSCLC patients. Our data strongly suggest adapting the guidelines and using dichotomous ALK-IHC as standard companion diagnostic test to select NSCLC patients that benefit from ALK-targeting therapy.

Originele taal-2English
Pagina's (van-tot)4251-4258
Aantal pagina's9
TijdschriftClinical Cancer Research
Volume23
Nummer van het tijdschrift15
Vroegere onlinedatum19-mei-2017
DOI's
StatusPublished - 1-aug.-2017

Vingerafdruk

Duik in de onderzoeksthema's van 'Dichotomous ALK-IHC Is a Better Predictor for ALK Inhibition Outcome than Traditional ALK-FISH in Advanced Non-Small Cell Lung Cancer'. Samen vormen ze een unieke vingerafdruk.

Citeer dit