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MINI 08 - Prognostic/Predictive Biomarkers (ID 106)
- Event: WCLC 2015
- Type: Mini Oral
- Track: Biology, Pathology, and Molecular Testing
- Presentations: 1
- Moderators:T.E. Stinchcombe, N. Pavlakis
- Coordinates: 9/07/2015, 16:45 - 18:15, Mile High Ballroom 4a-4f
MINI08.05 - A Survival Comparison Study of Chinese Patients with Primary Lung Adenocarcinoma Harboring ALK Rearrangements Detected in Different Methods with Crizotinib Treatment (ID 3227)
16:45 - 18:15 | Author(s): Z. Zhou
EML4-ALK is a new driver gene of non-small cell lung cancer (NSCLC) and is associated with response to inhibition with crizotinib. ALK break apart fluorescence in situ hybridization (FISH) assay, Ventana immunohistochemistry (IHC), and reverse transcriptase polymerase chain reaction (RT-PCR) can all be used as the primary assay for detecting ALK fusion events in tumor samples of lung cancer patients with SFDA approval in China. The objective of this study was to analyze the association of ALK rearrangements with clinical outcomes in different ALK testing methods, including FISH, Ventana IHC, and RT-PCR.
ALK status was assessed by FISH, IHC and RT-PCR in 75 patients with advanced ALK-positive lung adenocarcinoma who had received crizotinib treatment from 2011, May to 2014, Nov in China. Clinicopathologic data and survival outcomes were analyzed. Kaplan-Meier cumulative probability was used to assess different testing methods for survival.
Of all 75 ALK-positive lung adonocarcinoma, there are 23 FISH-positive ALK patients (23/75, 30.7%), 35 IHC-positive ALK patients (35/75, 46.7%) and 17 RT-PCR-positive ALK patients (17/75, 22.7%). 75 patients received crizotinib treatment with IHC-positive and FISH-positive had better progression-free survival (PFS) (P=0.049, Fig A), compared with those with RT-PCR-positive, but not for overall survival (OS) (P=0.074). The median PFS survival for all these 75 patients was 16m, 14m, 8m, respectively, based on the IHC, FISH, and RT-PCR test (Fig A). 23 patients received first-line crizotinib treatment with IHC-positive and FISH-positive had better PFS (P=0.030), compared with those with RT-PCR-positive, but not for OS (P=0.061), either. The median PFS survival for these 23 patients with first-line crizotinib treatment was 12m, 18m, 4.8m, respectively, based on the IHC, FISH, and RT-PCR test. Of all 17 RT-PCR-positive ALK patients, there are 10 E13:A20 fusion type (10/17, 58.8%), 4 E6:A20 fusion type (4/17, 23.5%), 2 E18:A20 fusion type (2/17, 11.8%), and 1 E2:A20 fusion type (1/17, 5.9%). 4 different fusion-type ALK-positive patients detected by RT-PCR received crizotinib treatment with no crizotinib-related PFS significant difference (P=0.312) and no OS difference (P=0.149).Figure 1
ALK-positive patients confirmed by IHC and FISH assay, compared with RT-PCR, maybe have better crizotinib-related PFS. RT-PCR method needs to be further evaluated in clinical practice to identify its role in guiding targeted therapy using crizotinib. And there is no survival difference for different ALK fusion type detected by RT-PCR in our cohort, which need further validation in a large group.
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