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Y. Wu



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    Poster Display Session (ID 63)

    • Event: ELCC 2017
    • Type: Poster Display Session
    • Track:
    • Presentations: 2
    • Moderators:
    • Coordinates: 5/07/2017, 12:30 - 13:00, Hall 1
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      141TiP - ASTRIS: A multicenter, real world treatment study of osimertinib in EGFR T790M positive non-small cell lung cancer (NSCLC) (ID 278)

      12:30 - 13:00  |  Author(s): Y. Wu

      • Abstract

      Background:
      EGFR tyrosine kinase inhibitors (TKIs) are the first-line treatment for patients with EGFR mutation positive advanced NSCLC. Resistance develops due to a secondary EGFR T790M mutation in approximately 60% of cases. Osimertinib is an oral, irreversible, central-nervous system (CNS) active, EGFR-TKI selective for both EGFR-TKI sensitising and T790M resistance mutations. In a Phase III trial versus platinum-based doublet chemotherapy in patients with T790M positive NSCLC (AURA3), osimertinib provided a significantly longer progression-free survival (PFS; median 10.1 mths vs. 4.4 mths; hazard ratio 0.30; 95% CI 0.23, 0.41; p < 0.001) and higher response rates (71% vs 31%; odds ratio 5.39; p < 0.001) (Mok et al, New Engl J Med 2016). Currently, there is limited evidence of the efficacy of osimertinib outside of clinical trials.

      Trial design:
      ASTRIS is a Phase III open-label, single-arm, multi-national, real world treatment study assessing the efficacy and safety of osimertinib in patients with advanced T790M mutation positive NSCLC, who have previously received an EGFR-TKI. Approximately 3500 patients will be enrolled across Asia, Europe and North and South America on a rolling basis. Country level enrolment is to stop within 6 months of market licence approval or national reimbursement. Key inclusion criteria are adults with locally advanced or metastatic NSCLC having a confirmed T790M mutation who received a prior EGFR-TKI and have World Health Organization performance status 0 − 2. T790M status must be confirmed by an appropriately validated test. Patients with asymptomatic CNS metastases, not requiring an increasing corticosteroid dose within 2 weeks prior to osimertinib administration, are allowed. Osimertinib 80 mg will be administered orally once daily for as long as the patient continues to receive clinical benefit, as judged by the investigator. The primary efficacy outcome is overall survival: secondary outcomes include investigator assessed response rate, PFS, and time to treatment discontinuation. Baseline demographics and disease characteristics, T790M mutation testing results and safety will also be reported.

      Clinical trial identification:
      NCT02474355 (27 May 2015)

      Legal entity responsible for the study:
      AstraZeneca

      Funding:
      AstraZeneca

      Disclosure:
      P.K. Cheema: Advisory board: Astrazeneca, Bristol Myers Squibb, Novartis, Boehringer Ingelheim, Pfizer, Merck Research sponsors: Astrazeneca, Hoffmann La Roche, Boehringer Ingelheim. Y-M. Chen: Advisory board of AstraZeneca, Boehringer Ingelheim, Roche and Merck Sharp & Dohme. H.C. Freitas: Member of ASTRIS steering committee, a research program supported by Astra Zeneca. A. Milner: Employee of AstraZeneca, who sponsored the study. M. Provencio: Honoraria for consultancy work from MSD, Bristol-Myers Squibb, Roche and Astrazeneca. J. Rigas: Consultant, through Kelly Service, for AstraZeneca in Global Medical Affairs on osimertinib (TAGRISSO). Y-L. Wu: Speaker fees from AstraZeneca, Roche, Eli Lilly. All other authors have declared no conflicts of interest.

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      146TiP - EXalt3: A phase III study of ensartinib (X-396) in anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC) (ID 473)

      12:30 - 13:00  |  Author(s): Y. Wu

      • Abstract

      Background:
      Ensartinib is a novel, potent anaplastic lymphoma kinase (ALK) small molecule tyrosine kinase inhibitor (TKI) with additional activity against MET, ABL, Axl, EPHA2, LTK, ROS1 and SLK. Ensartinib has demonstrated activity in ALK treatment naïve and previously treated patients and has a generally well tolerated safety profile.

      Trial design:
      eXalt3 (NCT02767804) is a global, randomized, open-label phase III study comparing the efficacy and safety of ensartinib to crizotinib in ALK- positive TKI naïve non-small cell lung cancer (NSCLC) patients. It is being conducted in > 100 sites in North America, South America, Europe, and the Asia/Pacific region. Enrollment began in 2016. The primary efficacy endpoint is progression free survival (PFS) assessed by independent radiology review. Secondary efficacy endpoints include overall survival, response rates (overall and central nervous system [CNS]), PFS by investigator assessment, time to response, duration of response, and time to CNS progression. Approximately 270 patients with ALK+ NSCLC who have received no prior ALK TKI and up to one prior chemotherapy regimen will be randomized 1:1 to ensartinib 225 mg QD, or crizotinib 250 mg BID, with stratification based on prior chemotherapy, ECOG performance status (PS), CNS metastases and geographic region. Eligibility includes patients ≥ 18 years of age, stage IIIB or IV ALK+ NSCLC. Patients are required to have measurable disease per RECIST 1.1, adequate organ function, and an ECOG PS of ≤ 2. Adequate tumor tissue (archival or fresh biopsy) must be available for central testing. The study has >80% power to detect a superior effect of ensartinib over crizotinib in PFS at a 2-sided alpha level of 0.05.

      Clinical trial identification:
      NCT02767804

      Legal entity responsible for the study:
      Xcovery Holding Company

      Funding:
      Xcovery Holding Company

      Disclosure:
      L. Horn: Consulting for Xcovery Holding Company, BMS, BI, Abbvie, Genentech, Merck. Y-L. Wu: Speaker fees from AstraZeneca, Roche, Eli Lilly. M. Reck: Honoraria for lectures and consultancy: Hoffmann-La Roche, Lilly, BMS, MSD, AstraZeneca, Merck, Celgene, Boehringer-Ingelheim, Pfizer, Novartis. C. Liang, K. Harrow, V. Oertel, G. Dukart: Full-Time Employee- Xcovery Holding Company. F. Tan: Manager- Xcovery Holding Company Chief Medical Officer- Betta Pharmaceuticals. T.S.K. Mok: Grant/Research Support from AstraZeneca, BI, Pfizer, Novartis, SFJ, Roche, MSD, Clovis Oncology, BMS, Eisai, Taiho; Speaker’s fees with: AstraZeneca, Roche/Genentech, Pfizer, Eli Lilly, BI, MSD, Novartis, BMS, Taiho; Major Stock Shareholder in: Sanomics Ltd.; Advisory Board for: AstraZeneca, Roche/Genentech, Pfizer, Eli Lilly, BI, Clovis Oncology, Merck Serono, MSD, Novartis, SFJ Pharmaceutical, ACEA Biosciences, Inc., Vertex Pharmaceuticals, BMS, geneDecode Co., Ltd., OncoGenex Technologies Inc., Celgene, Ignyta, Inc.; Board of Directors: IASLC, Chinese Lung Cancer Research Foundation Ltd., Chinese Society of Clinical Oncology (CSCO), Hong Kong Cancer Therapy Society (HKCTS).

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    Targeted therapies and immunotherapies (ID 46)

    • Event: ELCC 2017
    • Type: Poster Discussion session
    • Track:
    • Presentations: 1
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      92PD - First-line afatinib for advanced EGFRm+ NSCLC: Analysis of long-term responders (LTRs) in the LUX-Lung (LL) 3, 6 and 7 trials (ID 299)

      14:45 - 15:45  |  Author(s): Y. Wu

      • Abstract

      Background:
      In the Phase III LL3 and LL6 trials, first-line afatinib significantly improved PFS and ORR versus platinum-doublet chemotherapy in pts with EGFRm+ NSCLC. In the Phase IIb LL7 trial, afatinib significantly improved PFS, time to treatment failure, and ORR versus gefitinib in this setting. Here we present post-hoc analyses of afatinib LTRs (treated with afatinib ≥3 years) in LL3/6/7.

      Methods:
      Treatment-naïve pts with stage IIIB/IV EGFRm+ NSCLC who were randomized to 40 mg/day afatinib in LL3/6/7 were included.

      Results:
      24/229 (10%), 23/239 (10%) and 19/160 (12%) afatinib-treated pts in LL3, LL6 and LL7 were LTRs; 6, 9 and 14 LTRs were still on treatment at the time of analysis. In LL7, 4% of gefitinib-treated pts were LTRs. Baseline characteristics were generally consistent with the overall study populations, with the exception of greater proportions of women (LL3/6 only; 92/78% vs 64% in the overall populations) and Del19+ pts (63–79% vs 49–58% overall) among LTRs. The table shows treatment duration and outcomes. The median OS values for LL3/6 were >30 months longer than those reported in the overall populations. ORRs ranged from 70.8% in LL3 to 89.5% in LL7. Frequency and duration of subsequent therapy was similar to the overall population. Frequency of afatinib dose reduction due to TRAEs was broadly consistent with the overall populations; final afatinib doses of 20/30/40/50 mg were observed in 50/25/21/4% in LL3, 13/22/61/4% in LL6, and 32/21/47/0% in LL7.

      Conclusions:
      In the LL3/6/7 studies, 10–12% of afatinib-treated pts were LTRs (treated ≥3 years). Among these pts, greater proportions of women (LL3/6 only) and Del19+ NSCLC were observed. In LTRs, afatinib conferred a long-term survival benefit of ∼5 years and was well tolerated. Long-term treatment was independent of tolerability-guided dose adjustment, or the presence of brain metastases at time of enrolment, and had no detrimental impact on subsequent treatment.rnTable: 92PDrn

      rnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrn rnrn
      CharacteristicLL3 (n = 24)LL6 (n = 23)LL7 (n = 19)
      Median follow-up for OS, months64.657.042.1
      Median duration of treatment, months (range)50 (41–73)56 (37–68)42 (37–50)
      Median PFS (central review), months37.530.627.6
      Median OS, months63.255.340.8
      Overall response rate (CR+PR), n (%)17 (70.8)18 (78.3)17 (89.5)
      CR, n (%)1 (4.2)3 (13.0)1 (5.3)
      PR, n (%)16 (66.7)15 (65.2)16 (84.2)
      SD, n (%)5 (20.8)2 (8.7)2 (10.5)
      NN, n (%)2 (8.3)3 (13.0)–
      Median duration of response, months34.528.319.4
      rnCR, complete response; NN, not-PR/not-SD; PR, partial response; SD, stable diseasern

      Clinical trial identification:
      LUX-Lung 3: EudraCT No: 2008-005615-18 LUX-Lung 6: clinicaltrials.gov ref: NCT01121393 LUX-Lung 7: EudraCT No: 2011-001814-33

      Legal entity responsible for the study:
      Boehringer Ingelheim

      Funding:
      Boehringer Ingelheim

      Disclosure:
      M. Schuler: Advisory boards: AstraZeneca, Boehringer Ingelheim, Celgene, Eli Lilly, Novartis; Corporate-sponsored research: Boehringer Ingelheim, Bristol-Myers Squibb, Novartis; Honoraria: AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Eli Lilly, Novartis, Roche, MSD, Alexion; Patents: University Duisburg-Essen. L. Paz-Ares: Honoraria from Pfizer, Bristol-Myer Squibb, MSD, Novartis, Roche, Eli Lilly, Boehringer Ingelheim, Clovis Oncology, AstraZeneca, and Amgen. L.V. Sequist: Participated on advisory boards for Boehringer Ingelheim, AstraZeneca, Novartis, Clovis Oncology, Genentech, Merrimack, Ariad, and Bristol-Myers Squibb. S.L. Geater: Participated in advisory boards for Novartis and Boehringer Ingelheim, and has also received honoraria from Roche, AstraZeneca, Boehringer Ingelheim, and Novartis. A. Märten: Employee of Boehringer Ingelheim. J. Fan: Boehringer Ingelheim Pharmaceuticals Inc. employee. K. Park: Participated on advisory boards for Astellas, AstraZeneca, Boehringer Ingelheim, Clovis Oncology, Eli Lilly, Hanmi, MSD, Novartis, and Roche. J.C-H. Yang: Ad board and honoraria: BI, Lilly, Bayer, Roche/Genentech/Chugai, Astellas, MSD, Merck Serono, Pfizer, Novartis, Clovis, Celgene, Merrimack, Yuhan Pharmaceuticals, BMS, Ono pharmaceutical Daiichi, Sankyo, and AZ. All other authors have declared no conflicts of interest.