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Hiroaki Motomura

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    P1.03 - Chemotherapy/Targeted Therapy (ID 689)

    • Event: WCLC 2017
    • Type: Poster Session with Presenters Present
    • Track: Chemotherapy/Targeted Therapy
    • Presentations: 1
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      P1.03-006 - Clinicopathological Features and Poor Outcome for ALK Inhibitors of Squamous Cell Lung Cancer with ALK-Rearrangement (ID 8738)

      09:30 - 16:00  |  Presenting Author(s): Hiroaki Motomura

      • Abstract
      • Slides

      Anaplastic lymphoma kinase (ALK)-rearrangements are mainly encountered in 5% of adenocarcinomas lung cancer (Ad-LC) patients and anti-ALK targeted therapy dramatically improves therapeutic responses. The prevalence of ALK rearrangement in squamous cell lung carcinomas (Sq-LC) is extremely rare and thus, clinicopathological features and clinical outcomes for ALK inhibitors of ALK-rearranged Sq-LC were still unknown. Accordingly, in this study, we compared clinical features and clinical outcomes in patients with Sq-LC and Ad-LC.

      We retrospectively analysed the clinical features of five patients with ALK-rearranged Sq-LCs including two ALK-rearranged adenosquamous cell lung carcinomas (AdSq-LC) and compared the results with ALK-rearranged Ad-LC. We also evaluated representative cases of both responder and nonresponder to ALK inhibitors.

      The prevalence of ALK rearrangement in Sq-LCs was 1.36%. The population in ALK rearrangement NSCLC with smoking history was higher in ALK-rearranged Sq-LC than in ALK-rearranged Ad-LCs (80.0% and 68.0%). Progression-free survival (PFS) after initial treatment with the ALK inhibitor crizotinib was significantly shorter in ALK-rearranged Sq-LC than in ALK-rearranged Ad-LC (6.4±4.7 months and 13.4±12.8 months: p=0.033). Notably, two ALK fluorescence in situ hybridization (FISH)-positive/immunohistochemistry-negative cases did not respond to crizotinb, and PFS following alectinib treatment of ALK-rearranged Sq-LC was short (p = 0.045). The responder to ceritinib showed the presence of the L1196M mutation, which causes other ALK inhibitor resistance, by rebiopsy and successes to maintain CR response, even if detected off-target resistance marker of both EGFR and vimentin, a marker of EMT, for ALK inhibitors. However, the nonresponder did not respond to all ALK inhibitors, despite the presence of ALK FISH-positive circulating tumor cells and circulating free DNA without the mutation for ALK inhibitors resistance by liquid-biopsy.

      ALK-rearranged Sq-LC was associated with poor outcomes in ALK inhibitor-treated patients, suggesting that complexity of resistance mechanisms including off-target mechanisms for ALK inhibitors may exist. Oncologists should be aware of the possibility of ALK-rearranged Sq-LC based on clinicopathological features and plan the next therapeutic strategy by as much of re-biopsy accordingly to improve clinical outcomes.

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