Abstract 4244: Comparison of different ALK tests in non-small cell lung cancer (NSCLC) patients treated with crizotinib and their clinical outcome

Abstract

Abstract Background: The screening algorithm for detection of ALK-rearranged NSCLC is still under investigation. The Break-Apart ALK FISH is the standard diagnostic test for the treatment with crizotinib. However, immunohistochemistry (IHC) with different antibodies shows excellent results when compared to ALK FISH. The efficacy of crizotinib is studied in relation to ALK FISH. We compared IHC outcome and the number of ALK breaks estimated with FISH with clinical outcome. Methods: Patients treated with crizotinib who had biopsies with sufficient tumor tissue were selected. Tumour response was assessed by CT using RECIST. Fluorescence in situ hybridization (FISH) was performed with Vysis LSI ALK Break Apart FISH Probe KIT (Abbott Molecular) and immunohistochemistry with Ventana ALK IHC Kit using D5F3 antibody. Results: Twenty one patients with NSCLC were selected, median (range) age 54 yrs (21-75); 19 had adenocarcinoma, 2 had large-cell carcinoma. We confirmed the presence of EML4-ALK fusions in all samples either by FISH or IHC. Median percentage of ALK breaks was 47% (6-76). Tumour response occurred in 12 pts having a median of 51 (6-76) breaks and 9 non-responders having a median of 27 (15-64) breaks. Of the 12 responders, 8 pts had positive IHC (67%), 3 were negative and 1 was not done; the FISH negative, IHC positive patient was one of the responders. Of the 9 non-responders 2 had positive IHC (22%), 3 negative (33%), and 1 was equivocal and 3 not done. Median PFS for positive IHC is 7.9 mo (95% CI., 5.5 - 10.3) and for negative IHC 1.6 mo (1.3 - 1.8), n = 17, p<0.0001. OS survival data are 6.5 mo (95% CI., 0 - 17.8) and 18.3 mo (95% CI., 11.1 - 25.6) respectively, n = 17 p = 0.052. PFS above 30% number of breaks was 7.0 mo (95% CI., 1.8 - 12.2) versus PFS below is 1.8 mo (95% CI., 0.7 - 2.9), n = 21, p = 0.05. OS survival data are 4.1 mo (95% CI., 0 - 9.3) and 16.1 mo (95% CI., 9.0 - 23.2) respectively, n = 21 p = 0.003. Therefore PFS and OS is more prolonged in those tumors who have ALK breaks above 30%. IHC difference are only significant for PFS. Conclusions: Both ALK FISH and IHC identify NSCLC patients who benefit from crizotinib treatment. Patients with ALK breaks above 30% have a better PFS and OS. IHC only differentiates for PFS. Citation Format: Anthonie J. van der Wekken, Thijo JN Hiltermann, Wim Timens, Ed Schuuring, Harry JM Groen. Comparison of different ALK tests in non-small cell lung cancer (NSCLC) patients treated with crizotinib and their clinical outcome. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4244. doi:10.1158/1538-7445.AM2015-4244