Author of

• 20152

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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
  • Moderators:
  • Coordinates: 10/16/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)

  • 22564

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    P1.03-009 - A Lung Adenocarcinoma with a STRN-ALK Rearrangement Was Poorly Responsive to Alectinib Treatment (ID 9197)

    09:30 - 09:30  |  Author(s): T. Nishizawa
    • Abstract

    Background:
    Patients with advanced-stage non-small cell lung cancer (NSCLC) can receive benefits from treatment with anaplastic lymphoma kinase (ALK) inhibitors, if the tumor harbors a rearrangement of the ALK-encoding gene. Alectinib, a second-generation ALK inhibitor, is generally an effective therapy for ALK-rearranged NSCLC, but not all patients are responsive to Alectinib treatment. The aim of the present study was to assess the clinical and genetic characteristics of ALK-positive lung adenocarcinoma (ADC) that showed poor response to Alectinib treatment.
    
    Method:
    Patients with ALK-rearranged NSCLC, who received Alectinib treatment at Nihon University Itabashi Hospital (Tokyo, Japan) between 2015 and 2017, were included in the study. Demographic and clinical data including year, sex, stage, smoking history, treatment response, and survival were collected. Pleural effusion from a poorly responsive patient was further examined for secondary ALK mutations and ALK fusion partners. Secondary ALK mutations were analyzed using Sanger sequencing, and ALK fusion partners were identified by RNA sequencing. Furthermore, p-glycoprotein (p-gp)/ATP binding cassette subfamily B member 1 (ABCB1) mRNA levels were quantified by quantitative RT-PCR. The study was approved by the institutional review board.
    
    Result:
    Five patients (three men and two women; median age, 51 years) with adenocarcinoma were studied. Two patients received first-line treatment, two received second-line treatment, and one received fourth-line treatment. Four patients achieved partial response, and one patient did not respond to the treatment. The median progression-free survival (PFS) rate was 204 days. In the poorly responsive patient, PFS rate was 92 days, which was much shorter than previously reported. No secondary gatekeeper mutations in the ALK tyrosine kinase domain was detected in carcinoma cells obtained from pleural effusion of one poorly responsive patient. However, Striatin (STRN)/ALK, a rare fusion of the aggressive rearranged ALK, was identified, it was confirmed that one end of STRN exon3 was fused with the beginning of ALK exon 20. ABCB1 overexpression was also detected.
    
    Conclusion:
    A rare ALK rearrangement, STRN/ALK, and overexpression of the multidrug-resistant ABCB1 are possible candidates for predictive factors for poor response to Alectinib treatment.