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Jon Kroll Bjerregaard



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    EP1.08 - Oligometastatic NSCLC (ID 198)

    • Event: WCLC 2019
    • Type: E-Poster Viewing in the Exhibit Hall
    • Track: Oligometastatic NSCLC
    • Presentations: 1
    • Now Available
    • Moderators:
    • Coordinates: 9/08/2019, 08:00 - 18:00, Exhibit Hall
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      EP1.08-07 - Correlation Between Genetic Profiling and Response in Danish ALK-Positive NSCLC Patients Treated with Crizotinib (Now Available) (ID 923)

      08:00 - 18:00  |  Author(s): Jon Kroll Bjerregaard

      • Abstract
      • Slides

      Background

      In 2011 Crizotinib received FDA approval for the treatment of ALK-positive NSCLC. Due to large diversity in clinical course of these patients, baseline genomic profiling at diagnostic biopsy was performed to find possible correlations with clinical features.

      Method

      We performed a retrospective analysis of 28 consecutive patients receiving Crizotinib for metastatic, immunohistochemistry (IHC)- and fluorescens in-situ hybridization (FISH)-determined ALK-positive NSCLC, between September 2011 and DATE. Clinical data were collected by chart review. DNA/RNA genomic profile were performed using the patients’ biopsy at the time of diagnosis or at initiation of therapy using targeted next-generation sequencing (NGS) Oncomine™ Focus (ThermoFisher Scientific) and Archer® Solid Tumor (ArcherDx) assays. Baseline clinical features and genetic information were correlated with overall survival and progression free survival.

      Result

      The cohort included 15 women and 13 men, median age 56 (range 22-83). Median PFS was 5.2 months (CI 2.9-9.5), median OS was 17.3 months (CI 8.8-33.2). Favorable prognostic factors for both PFS and OS were PS 0-1 vs 2 (n=25), male gender (n=13), never smoking (n=18) and up-front brain metastasis (n=6). Fourteen patients were treated with Crizotinib as 2nd line therapy and had better OS, but similar PFS. Crizotinib-responders (CR+PR+SD) represented 71% and -no responders (PD) 29%. Most patients received further treatment after progression on Crizotinib (68%). The most common ALK-fusion-partner was EML4 (64%; of which 50% were variant v1, 28% v2, 22% v3). For 8 patients (28%) no fusion partner was identified. In 7 cases (25%) the FISH-detected ALK-rearrangement was not confirmed by IHC and NGS and 4 of them did not respond, 1 case (4%) was FISH-/IHC-positive but NGS-negative and responded. Four of 8 non-responders (all 4 IHC-negative, 3 NGS-negative) showed another de novo gene-alteration (in KRAS, ALK or EGFR). Two patients with another fusion-partner: KIF5B(17)-ALK(20) and TEMP3(6)-ALK(20) had an aggressive clinical course after short-term response. In contrast, a patient with pre-existing ALK-mutations F1174L and R1275Q, had the longest duration of treatment with Crizotinib (2.5 years). Patients with EML4 fusion-partner (n=18) were prone to achieve better OS than the others. Rebiopsies at progression for 8 patients showed different TKI-resistance mechanisms.

      Conclusion

      ALK-positive NSCLC represents a heterogenous disease, which in most cases can be encapsulated by ALK-TKI. Although this small cohort does not allow to draw unambiguous conclusions, it does indicate that the efficacy of treatment may vary with different ALK-fusion-partners. Moreover, ALK-positive NSCLC should be validated and classified by NGS-testing at baseline to optimize the choice of ALK- TKI.

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