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Zhi Xie



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    MA15 - Colliding Approaches - EGFR and Immunotherapy (ID 916)

    • Event: WCLC 2018
    • Type: Mini Oral Abstract Session
    • Track: Targeted Therapy
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/25/2018, 13:30 - 15:00, Room 107
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      MA15.06 - Circulating Tumor DNA Portrays the Resistance Landscape to a Novel Third Generation EGFR Inhibitor, AC0010 (ID 13641)

      14:05 - 14:10  |  Author(s): Zhi Xie

      • Abstract
      • Presentation
      • Slides

      Background

      In a Phase I/II dose-escalation and expansion study conducted at Guangdong Lung Cancer Institute, AC0010 demonstrated promising efficacy and good tolerability in advanced NSCLC patients with EGFR T790M-mediated resistance to previous EGFR TKIs, (NCT02330367). As disease progression (PD) with EGFR T790M-directed therapy also emerges over time, we investigated the resistance mechanisms to AC0010 in this study.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      Serial ctDNA samples obtained from patients who developed PD with AC0010 were analyzed using ultra-deep sequencing capturing 295 cancer-related genes. Alterations that were absent before treatment and acquired at PD or that increased in abundance during treatment were identified as putative resistance mechanisms.

      4c3880bb027f159e801041b1021e88e8 Result

      Longitudinal plasma samples were obtained from 23 patients who progressed on AC0010 (data cut-off October 14, 2016; figure1). Putative resistance mechanisms to AC0010 were identified in 19/23 patients (>1 putative resistance mechanism was detected in some patients). EGFR amplification was the predominant resistance mechanism (21.1% [4/19 patients]), followed by TP53 loss of heterozygosity (15.8% [3/19]). EGFR C797S mutation, Met amplification and mutations in the PI3KCA pathway each occurred in 10.5% of patients (2/19). SCLC transformation, ERBB2 amplification, CD79A_A32G mutation, CDKN2A_R80 mutation, CRLF2 amplification, MLH1 amplification, Rb1 loss, and concurrent rise in the allelic fraction of tumor suppressor gene TP53 and Rb1 were each detected in 5.3% of patients (1/19). In a patient with PD following single-agent AC0010 and EGFR amplification as the putative resistance mechanism to AC0010, subsequent treatment with AC0010 plus nimotuzumab (EGFR monoclonal antibody) successfully overcame resistance, resulting in a response that lasted for 7.7 months.

      fig 1_study profile.jpg

      8eea62084ca7e541d918e823422bd82e Conclusion

      The resistance landscape to AC0010 appears to differ from that described previously with osimertinib. In this cohort of patients in China, EGFR amplification was the predominant resistance mechanism to AC0010 and could be potentially overcome by EGFR dual inhibition.

      6f8b794f3246b0c1e1780bb4d4d5dc53

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    P2.04 - Immunooncology (Not CME Accredited Session) (ID 953)

    • Event: WCLC 2018
    • Type: Poster Viewing in the Exhibit Hall
    • Track:
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/25/2018, 16:45 - 18:00, Exhibit Hall
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      P2.04-30 - PD-1/PD-L1 Inhibition Might be an Option for the Treatment of Advanced Primary Pulmonary Lymphoepithelioma-Like Carcinoma (ID 12698)

      16:45 - 18:00  |  Author(s): Zhi Xie

      • Abstract
      • Slides

      Background

      Primary pulmonary lymphoepithelioma-like carcinoma (LELC) is a rare subtype of non-small-cell lung cancer mostly reported in Asian countries, which is frequently associated with Epstein-Barr virus (EBV) infection. There is no consensus on the choice for the treatment of advanced primary pulmonary LELC. The utility of PD-1/PD-L1 inhibitor to this cancer type remains poorly understood.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      From January 2008 to April 2017, a total of 53 patients receiving surgical removal and diagnosed as primary pulmonary LELC in Guangdong Lung Cancer Institute (GLCI) were enrolled in this study. Sections formalin-fixed and paraffin-embedded (FFPE) tumor samples were stained with PD-L1 antibody (clone E1L3N, Cell Signaling Technology) by immunohistochemistry (IHC). PD-L1 expression more than 1% in tumor cells was considered as PD-L1 positive. Moreover, we reviewed the medical records of 13 primary pulmonary LELC patients who received the treatment of PD-1/PD-L1 inhibitors in GLCI. Their clinicopathological characteristics and relevant prognostic data were analyzed.

      4c3880bb027f159e801041b1021e88e8 Result

      Among the 53 patients with operable disease, the median age was 56 (36-78), there were 26 males and 27 females, 15 smokers and 38 nonsmokers. Positive rates of PD-L1 in the early pulmonary LELC were 78.8% (41/52,one specimen can't evaluate) and 73.1% (38/52) and 23.1% (12/52) respectively at the cutoff values of 1% and 5% and 50% positivity in tumor cells. ORR of PD-1/PD-L1 inhibition in the evaluable 12 patients with advanced LELC was 16.7% (2/12), and DCR was 75.0% (9/12). In the 6 patients with positive PD-L1 expression, ORR was 33.3% (2/6), DCR was 100.0% (6/6). The two responder patients got 55% and 64% shrinkage of the tumors respectively. All patients had no EGFR mutations.

      io in lelc1.tif

      8eea62084ca7e541d918e823422bd82e Conclusion

      This preliminary study showed that pulmonary LELCs have remarkably high incidence of PD-L1 expression. PD-1/PD-L1 inhibitors might be an option for the treatment of advanced primary pulmonary LELC, which needs further investigation.

      6f8b794f3246b0c1e1780bb4d4d5dc53

      Only Active Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login or select "Add to Cart" and proceed to checkout.