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N. Yamamoto



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    Immunotherapy and next-generation TKIs: From second to frontline treatment (ID 55)

    • Event: ELCC 2018
    • Type: Poster Discussion session
    • Track:
    • Presentations: 1
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      141PD - A prospective study of molecular testing status in the EGFR mutation positive NSCLC patients with disease progression during EGFR TKI treatment (REMEDY study) (ID 167)

      07:45 - 09:00  |  Author(s): N. Yamamoto

      • Abstract
      • Slides

      Background:
      Although EGFR tyrosine kinase inhibitors (EGFR-TKI) provide significant clinical benefit in patients with EGFR-mutant non–small cell lung cancer (NSCLC), approximately 50–60% of the patients will acquire resistance by the T790M mutation. Osimertinib is a third generation EGFR-TKI and standard of care for patients whose tumor developed the acquired resistance by T790M mutations during the prior EGFR-TKI treatments. Eligibility for treatment with osimertinib will be dependent on mutation status determined by a validated diagnostic test based on a tumor tissue or a plasma. In order to avoid the risk of false negative, the Japan Lung Cancer Society's guidance on the EGFR mutation test recommends prioritizing tissue sample over plasma sample. Moreover, in case of T790M negative by prior plasma test, it also recommends to re-confirm by tissue test if it can be obtained. We conducted this study to investigate the real world practice of sample collection and T790M testing around the time of plasma testing approval in Japan.

      Methods:
      This is multicenter collaborative prospective observational study in Japan. Patients diagnosed with EGFR mutation-positive advanced NSCLC and whose progression of the disease (PD) was observed during EGFR-TKI treatment were enrolled. The primary endpoints are 1. the sample collection rate for EGFR T790M mutation test at PD, 2. EGFR T790M gene mutation testing and 3. the EGFR T790M detection rate. In addition, treatment information before and after PD were investigated.

      Results:
      In previously reported interim analysis of 111 patients, sample collection was performed in 104 cases (93.7%). Regarding collected sample type, tissue sample were collected from 19 patients, cytology sample from 14 patients and plasma sample from 71 patients. EGFR T790M mutation test was conducted in 103 cases (92.8%). T790M mutation detection rate in patients who were obtained adequate tissue sample were 43.8% (7/16) and higher than cytology (21.4%; 3/14) and plasma (22.5%; 16/71). Sixty-one percent (43/71) of the patients tested by plasma were ctDNA “non-shedders” (no detectable EGFR mutation).

      Conclusions:
      In this presentation, we report final full results of total 243 registered cases.

      Clinical trial identification:
      UMIN ID; 000024928

      Legal entity responsible for the study:
      This study was conducted by AstraZeneca KK

      Funding:
      Has not received any funding

      Disclosure:
      N. Yamamoto: Personal fees from AstraZeneca, during the conduct of the study; personal fees from Chugai Pharmaceutical, Boehringer Ingelheim, Eli Lilly, and Pfizer, outside the submitted work. N. Nogami: Personal fees from Meiji Seika Pharama., AstraZeneca KK, Pfizer Inc., Bristor-Myers Squibb, ONO Pharmaceutical Co., Ltd, Kyowa Hakko Kirin, TAIHO Pharmaceutical Co., Ltd, CHUGAI Pharmaceutical Co., Ltd, Eliy Lilly Japan and Boehringer Ingelheim. S. Atagi: Personal fees from AstraZeneca KK, Boehringer Ingelheim, Bristol-Myers Squibb, Chugai, Lilly, Ono and Taiho and contract research with AstraZeneca KK, Boehringer Ingelheim, Chugai, Lilly, Merck Serono, Ono, Pfizer, Taiho and Yakult and consultant fee from AstraZeneca KK. H. Saka: Personal fees from AstraZeneca KK and contract research with AstraZeneca KK. and is a representative of NPO Central Japan Lung Study Group. N. Tashiro: Employee of AstraZeneca KK. T. Seto: Grants(G): Astellas, Bayer, Merck Serono, Novartis, Verastem. Personal fees(PF): BMS, Kissei, Kyowa Hakko Kirin, Nippon Kayaku, Ono, Roche, Sanofi, Showa, Sumitomo Dainippon, Taiho, Takeda and other 3. G and PF: AstraZeneca, Chugai, Daiichi Sankyo, Eisai, Eli Lilly, MSD, BI, Pfizer, Yakult. All other authors have declared no conflicts of interest.

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    Poster Display session (Friday) (ID 65)

    • Event: ELCC 2018
    • Type: Poster Display session
    • Track:
    • Presentations: 1
    • Moderators:
    • Coordinates: 4/13/2018, 12:30 - 13:00, Hall 1
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      158P - Afatinib in patients with EGFR mutation-positive (EGFRm+) NSCLC harbouring uncommon mutations: Overview of clinical data (ID 567)

      12:30 - 13:00  |  Author(s): N. Yamamoto

      • Abstract
      • Slides

      Background:
      Approximately 10–12% of patients with EGFRm+ NSCLC have tumours harbouring uncommon EGFR mutations; however, there is a paucity of clinical data on the sensitivity of these tumours to EGFR TKIs. Preclinical data indicate that the irreversible ErbB family blocker, afatinib, has similar activity against certain uncommon mutations (e.g. L858M/S768I) to that against the common L858R mutation.[1,2]

      Methods:
      Here, we review the key clinical data available for first-line afatinib in EGFRm+ NSCLC harbouring uncommon EGFR mutations.

      Results:
      Post-hoc analysis of the randomised LUX-Lung 2/3/6 trials[3] demonstrates that afatinib is clinically active against certain uncommon EGFR mutations. Among 75 afatinib-treated patients with tumours harbouring uncommon mutations in these trials the objective response rate against G719X (n = 18), L861Q (n = 16) and S768I (n = 8) single/compound mutations was 78%, 56% and 100%. Response rate was lower in patients with exon 20 insertions (n = 23; 9%) or de novo T790M (n = 14; 14%). In 38 patients with uncommon mutations/duplications in exons 18–21 PFS was 10.7 months (95% CI 5.6–14.7) and OS was 19.4 months (95% CI 16.4–26.9). The clinical activity of afatinib against uncommon mutations is substantiated by observations outside of the randomised controlled trial setting. In a Phase IIIb single-arm open-label study of afatinib in its registered indication, 67 of 479 TKI-naïve patients had NSCLC with uncommon mutations[4] (exon 20 insertions; L861Q; G719S/A/C; T790M; S768I: 5.2; 4.6; 2.3; 1.0; 1.9%, respectively). Median PFS in these patients was 9.1 months (95% CI 5.6–13.6).[4] In an analysis of 165 EGFRm+ NSCLC patients treated with first-line afatinib in real-world practice in South Korea median PFS in those with uncommon mutations excluding T790M (n = 10) was not reached vs 4.7 months in those with T790M (n = 4; p = 0.01).[5]

      Conclusions:
      Afatinib has shown preclinical and clinical activity in patients with NSCLC harbouring uncommon EGFR mutations, including G719X, L861Q and S768I. These data could help inform clinical decisions in this patient population. 1. Saxon. J Thorac Oncol 2017;12:884 2. Banno. Cancer Sci 2016;107:1134 3. Yang. Lancet Oncol 2015;16:830 4. Wu. WCLC 2017 P3.01-036 5. Kim. WCLC 2017 P3.01-023

      Clinical trial identification:
      N/A

      Legal entity responsible for the study:
      Boehringer Ingelheim

      Funding:
      Boehringer Ingelheim

      Disclosure:
      A. Märten: Employment: Boehringer Ingelheim. N. Yamamoto: Membership on an advisory board or board of directors: BI, AZ, Chugai Corporate-sponsored research: BI. C-J. Yu: Membership on an advisory board or board of directors: Roche, ONO, Chugai, Novartis. Y-L. Wu: Honoraria: AstraZeneca, Roche, Eli Lilly, Pfizer, Sanofi. All other authors have declared no conflicts of interest.

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