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R. Liu

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    P1.01 - Advanced NSCLC (ID 757)

    • Event: WCLC 2017
    • Type: Poster Session with Presenters Present
    • Track: Advanced NSCLC
    • Presentations: 1
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      P1.01-003 - Patients Harboring a Novel PIK3CA Point Mutation after Acquired Resistance to Crizotinib in ROS1 Rearrangement Adenocarcinoma: A Case Report (ID 8245)

      09:30 - 16:00  |  Author(s): R. Liu

      • Abstract
      • Slides

      The c-ros oncogene 1 receptor tyrosine kinase (ROS1) rearrangement has been identified in 1%-2% of non-small cell lung cancer (NSCLC) cases, these patients would benefit from the inhibitor of anaplastic lymphoma kinase (ALK), crizotinib. But the resistance to crizotinib inevitably developed in the patients with ROS1 rearrangement NSCLC and shown a response to crizotinib initially. The mechanism of acquired resistance to crizotinib for the patients with ROS1 rearrangement NSCLC is not identified completely now.

      A 66-year-old female diagnosed with adenocarcinoma, who shown EGFR wild and ALK negative detected by Polymerase Chain Reaction(PCR). According to the detection of ROS1 rearrangement by the next generation sequencing (NGS) in blood after the patient received chemotherapy twice (pemetrexed and carboplatin), the addition of bevacizumab to chemotherapy 4 times (pemetrexed, carboplatin and bevacizumab) and maintenance therapy 3 times (pemetrexed and bevacizumab), crizotinib was used. Disease progressed explosively 6 months later, although the patient shown a response to crizotinib initially. Then NGS was carried out on blood again, a novel point mutation (p.L531P)of the PIK3CA gene was detected.

      This case was the second report for bypass activation conferred crizotinib resistance to the patient with ROS1 rearrangement NSCLC. And it also was the first report that confirmed mTOR signaling pathways activation would lead to acquired resistance to crizotinib in the clinical. And everolimus, the mTOR signaling pathway inhibitor, was used. However, the disease of the patient was too serious, and she still died of circulatory failure. In conclusion, progression-free survival was 5.0 months and overall survival was 16.0 months.

      Bypass activation is one of potential resistance mechanisms to ROS1 rearrangement NSCLC conferred crizotinib and regimen for mTOR signaling pathway inhibitor may be one of the treatment options.

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