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H. Groen



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    MINI 31 - ALK (ID 158)

    • Event: WCLC 2015
    • Type: Mini Oral
    • Track: Treatment of Advanced Diseases - NSCLC
    • Presentations: 1
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      MINI31.11 - Comparison of Different ALK Tests in Non-Small Cell Lung Cancer (NSCLC) Patients before and after Crizotinib and Their Clinical Outcome (ID 2687)

      18:30 - 20:00  |  Author(s): H. Groen

      • Abstract
      • Presentation
      • Slides

      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 by FISH with clinical outcome and retested at disease progression on crizotinib treatment

      Methods:
      Patients treated with crizotinib who had biopsies with sufficient tumor tissue were selected. Tumor response was assessed by CT using RECIST v1.1. Fluorescence in situ hybridization (FISH) was performed with Vysis LSI ALK Break Apart FISH Probe KIT (Abbott Molecular Inc., Des Plaines, IL) and immunohistochemistry with Ventana (Ventana Medical Systems Inc, Tucson, AZ) ALK IHC Kit using D5F3 antibody. The same tests were performed on re-biopsy material after progression on crizotinib.

      Results:
      Twenty-nine patients with ALK positive advanced NSCLC were treated with crizotinib. Median (range) age was 54 yrs (21-75); 26 had an adenocarcinoma, 3 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% (2-76). Tumor responses occurred in 9 pts having a median of 51 (6-76) breaks per tumor sample. The 20 non-responders had a median of 27 (15-64) breaks per tumor sample with 64 being an outlyer. In IHC positive pts 9/11 had a response to crizotinib treatment. In those who were IHC negative no pts (0/14) had a response (12 PD; 2 SD). 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. Overall survival is 6.5 mo (95% CI., 0 – 17.8) and 18.3 mo (95% CI., 11.1 – 25.6) respectively, n=29, p=0.05. In 8 pts with progressive disease re-biopsies were performed. Only in one pt FISH ALK became negative. In the other pts IHC and FISH remained both positive. In pts who progressed on crizotinib, 4 pts had extra red in the FISH, which may be treatment related.

      Conclusion:
      All IHC positive advanced NSCLC patients responded to crizotinib. Extra red in the FISH test may cause progression to treatment with crizotinib.

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