Abstract
Purpose:
ALK rearrangement detection using FISH is the standard test to identify patients with non–small cell lung carcinoma (NSCLC) 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 patients with advanced NSCLC with ALK activation using both dichotomous immunohistochemical (IHC) staining and FISH.
Experimental Design:
Patients with stage IV NSCLC 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 patients with ALK-FISH–positive advanced NSCLC from four 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. Receiver operator characteristic (ROC) curves for ALK-IHC and ALK-FISH compared with treatment outcome showed that dichotomous ALK-IHC outperforms ALK-FISH [tumor response area under the curve: (AUC), 0.86 vs. 0.64, P ¼ 0.03; progression-free survival (PFS): AUC 0.86 vs. 0.36, P ¼ 0.005; overall survival (OS): AUC, 0.78 vs. 0.41, P ¼ 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 patients with advanced NSCLC. Our data strongly suggest adapting the guidelines and using dichotomous ALK-IHC as standard companion diagnostic test to select patients with NSCLC who benefit from ALK-targeting therapy.
| Original language | English |
|---|---|
| Pages (from-to) | 4251-4258 |
| Number of pages | 8 |
| Journal | Clinical Cancer Research |
| Volume | 23 |
| Issue number | 15 |
| DOIs | |
| Publication status | Published - 1 Aug 2017 |
| Externally published | Yes |
Bibliographical note
Funding Information:A.J. van der Wekken has received speakers' bureau honoraria from and is a consultant/advisory board member for Pfizer. N.'t Hart is a consultant/advisory board member for Pfizer advisory meeting. L. Hendriks has received financial support for printing PhD thesis from Pfizer. E.H.F.M. van der Heijden reports receiving other commercial research support from Pentax Medical and Astra-Zeneca Oncology; has received speakers' bureau honoraria from MSD Oncology; and is a consultant/advisory board member for MediGlobe Corporation. S. Riemersma has received speakers' bureau honoraria from Lilly and is a consultant/advisory board member for Pfizer and Amgen. E.J.M. Speel is a consultant/advisory board member for Pfizer, Roche, MSD, and BMS. A.-M.C. Dingemans is a consultant/advisory board member for Pfizer and Roche. W. Timens is a consultant/advisory board member for MSD, Roche/Ventana, and Pfizer. E. Schuuring has received speakers' bureau honoraria from Novartis and Pfizer and is a consultant/advisory board member for Pfizer. H.J.M. Groen is a consultant/advisory board member for Pfizer and Roche. No potential conflicts of interest were disclosed by the other authors. For sending tumor tissue, we would like to acknowledge H. Sietsma, P. Nederlof, P. van Zwam, and E. Thunnissen. We are also grateful to Tineke van der Sluis, Geert Harms, and Jan Donga for technical assistance. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
Publisher Copyright:
©2017 AACR.
