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J.C. Yang



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    Management of brain metastases (ID 2)

    • Event: ELCC 2017
    • Type: Educational session
    • Track:
    • Presentations: 1
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      Systemic treatment of brain metastases (ID 3)

      14:30 - 16:00  |  Author(s): J.C. Yang

      • Abstract
      • Presentation
      • Slides

      Abstract not provided

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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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      100P - Afatinib vs gefitinib for treatment-naïve patients with EGFRm+ NSCLC (LUX-Lung 7): Analysis of time to treatment failure and impact of afatinib dose adjustment (ID 356)

      12:30 - 13:00  |  Author(s): J.C. Yang

      • Abstract

      Background:
      PFS was significantly improved in LUX-Lung 7 with afatinib (A) vs gefitinib (G). Time to treatment failure (TTF) was a co-primary endpoint to reflect clinical practice of continuing TKI tx beyond radiologic progression in the absence of clinical deterioration. An analysis of TTF and a post-hoc analysis of the impact of dose adjustment of A on PFS and AEs are reported here.

      Methods:
      Patients (pts) were randomized to A 40mg/d or G 250mg/d until progressive disease (PD) or beyond if deemed beneficial. The dose of A could be reduced by 10mg decrements to a minimum of 20mg in the event of selected drug-related (DR) AEs. TTF was analyzed using a stratified log-rank test and Kaplan-Meier methods. PFS was compared between pts who had a dose reduction within 6 mos and those who received ≥40mg for 6 mos. Incidence/severity of common AEs before/after dose reduction was assessed.

      Results:
      319 pts were randomized (160 A, 159 G). At data cut-off (21 Aug 2015), 87.5% A and 93.7% G pts had discontinued tx, mostly due to radiologic PD (69.4 vs 74.8%) or toxicity (11.3 vs 10.7%). 35.0% A and 29.6% G pts with clinical benefit continued tx beyond radiologic PD. Pts remained on tx significantly longer with A vs G (median TTF 13.7 vs 11.5 mos; HR 0.73 [95% CI 0.58–0.92]; p = 0.007; pts on tx at 2 yrs: 25.0 vs 13.2%). TTF subgroup analyses favored A. Risk of tx failure was reduced with A vs G regardless of EGFRm type or race. Median tx duration beyond PD with A and G was 2.7 and 2.0 mos, respectively. 63 pts (39%) treated with A had a dose reduction to 30mg; 21 (13%) had further reduction to 20mg. There was no significant difference in PFS in pts who received <40 mg or ≥ 40 mg (median 12.8 vs 11.0 mos; HR 1.3 [95% CI 0.9–2.0]; p = 0.14). Dose reduction of A reduced the incidence/severity of DR AEs: grade ≥3 diarrhea, rash/acne and stomatitis were reduced from 25.4%, 20.6% and 7.9%, to 9.5%, 3.2% and 3.2%, respectively.

      Conclusions:
      TTF was significantly improved with first-line A vs G in EGFRm+ NSCLC, which testifies to the tolerability of A, and suggests that it may confer additional clinical benefit in pts who continue tx beyond PD. Dose adjustment of A reduced the frequency/intensity of DR AEs without compromising efficacy.

      Clinical trial identification:
      LUX-Lung 7: EudraCT No: 2011-001814-33

      Legal entity responsible for the study:
      Boehringer Ingelheim

      Funding:
      Boehringer Ingelheim

      Disclosure:
      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. L. Paz-Ares: Honoraria from Pfizer, Bristol-Myers Squibb, MSD, Novartis, Roche, Eli Lilly, Boehringer lngelheim, Clovis Oncology, AstraZeneca, and Amgem. K. O\'Byrne: Ad board, speaker bureau, travel to international conferences and honoraria: AZ, BMS, Roche-Genentech, MSD, Pfizer, BI. Ad board and speaker bureau: Novartis. 3 Patents: 1 on novel drugs, 2 on biomarkers, IP held by Queensland University of Technology. M. Boyer: Ad board: BMS, Merck Sharpe and Dohme, Pfizer Board of Directors: IASLC Research: Pfizer, Genentech, BI, AZ, Novartis, Merck Sharpe and Dohme, Clovis Honoraria: Merck Sharpe and Dohme, BI, BMS, AZ. T. Mok: Receipt of grants/research supports: AstraZeneca, BI, Pfizer, Novartis, SFJ, Roche, MSD, Clovis Oncology, BMS; Receipt of honoraria or consultation fees: AstraZeneca, Roche/Genentech, Pfizer, Eli Lilly, BI, Merck Serono, MSD, Janssen, Clovis Oncology, BioMarin, GSK, Novartis, SFJ Pharmaceutical, ACEA Biosciences, Inc., Vertex Pharmaceuticals, BMS, AVEO & Biodesix, Prime Oncology, Amgen; Participation in a company sponsored speaker’s bureau: AstraZeneca, Roche/Genentech, Pfizer, Eli Lilly, BI, MSD, Amgen, Janssen, Clovis Oncology, GSK, Novartis, BMS, PrIME Oncology; Stock shareholder: Sanomics Limited. V. Hirsh: Honoraria for participating on advisory boards for Boehringer Ingelheim, AstraZeneca, Roche, Merck, Eli Lilly, Pfizer, Amgen, and Bristol-Myers Squibb. K. Park: Participated on advisory boards for Astellas, AstraZeneca, Boehringer Ingelheim, Clovis Oncology, Eli Lilly, Hanmi, MSD, Novartis, and Roche. All other authors have declared no conflicts of interest.

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      102P - LUX-Lung 8 phase III trial: Analysis of long-term response to second-line afatinib in patients with advanced squamous cell carcinoma (SCC) of the lung (ID 355)

      12:30 - 13:00  |  Author(s): J.C. Yang

      • Abstract

      Background:
      In LUX-Lung 8, afatinib (A; 40mg/day) significantly improved OS (median 7.9 vs 6.8 months, p = 0.008) and PFS (2.6 vs 1.9 months, p = 0.010) versus erlotinib (E; 150mg/day) in pts with pretreated SCC of the lung (n = 795). 12-month (36 vs 28%; p = 0.016) and 18-month survival (22 vs 14%; p = 0.013) were significantly higher with A than E, indicating that some pts derive prolonged benefit from A. This is a post-hoc analysis of baseline characteristics and efficacy/safety of A in long-term responders (LTRs; treatment for ≥12 months). Archived tumor samples and serum were analyzed to identify potential biomarkers.

      Methods:
      Tumor samples were retrospectively analyzed using next-generation sequencing (NGS); EGFR expression was determined by IHC. Pre-treatment serum samples were analyzed with VeriStrat[®] and classified as VeriStrat-Good or VeriStrat-Poor.

      Results:
      21/398 pts treated with A were LTRs. Six pts were still on treatment at the time of data cut-off. The median duration of treatment was 17.6 months (range: 12.3–27.6). Baseline characteristics were similar to the overall dataset (median age: 64 y [range: 54–81]; male: 76%; Asian: 29%; ECOG 0/1: 33%/67%; best response to chemotherapy CR or PR/SD: 48%/52%; current and ex-smokers: 90%). Median PFS was 16.6 months (range: 2.8–25.8); median OS was 21.1 months (12.9–31.6). The most common treatment-related AEs (all grade/grade 3) were: diarrhea (81%/5%); rash/acne (71%/5%); stomatitis (29%/5%). AEs generally occurred soon after treatment onset. Six pts had dose reductions due to related AEs. NGS data in ten LTRs will be presented. Genomic aberrations in the ErbB gene family were identified in 50% of these pts (overall dataset: 26.5%). Of 17 pts assessed by VeriStrat, 88% were VeriStrat-Good (overall dataset: 62%). IHC data were available for only one LTR (EGFR-).

      Conclusions:
      Baseline characteristics of LTRs to A were similar to the overall dataset. A conferred median OS of almost 2 years in this subgroup. A was well tolerated with predictable, transient AEs. Though biomarker data look promising, the cohort was too small to identify any clear NGS/VeriStrat predictive signals; further studies are required.

      Clinical trial identification:
      LUX-Lung 8: EudraCT No: 2011-002380-24

      Legal entity responsible for the study:
      Boehringer Ingelheim

      Funding:
      Boehringer Ingelheim

      Disclosure:
      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. G. Goss: Participated on advisory boards for AstraZeneca, Boehringer Ingelheim, Pfizer, Eli Lilly, Bristol-Myers Squibb, and Celgene. E. Felip: Participated on advisory boards for Eli Lilly, Pfizer, Roche, MSD, and Boehringer Ingelheim. Felip has receieved lecture fees from AstraZeneca, Bristol-Myers Squibb, and Novartis. A. Ardizzoni: Received honoraria and participated on advisory boards for Bristol-Myers Squibb, MSD, Eli-Lilly, and Boehringer Ingelheim. Ardizzoni has received honoraria from Pfizer and Bayer. S.M. Gadgeel: Participated on advisory boards for Boehringer Ingelheim, Pfizer, Genentech, ARIAD, AstraZeneca, Bristol-Myers Squibb, and Roche. N. Dupuis: Employee of and owns stock in Biodesix. E. Ehrnrooth: Employee of Boehringer Ingelheim. J-C. Soria: Astrazeneca, Astex, GSK, Gammamabs, Lilly, MSD, Merus, Pfizer, Pharmamar, Pierre Fabre, Roche, Sanofi, Servier, Symphogen, Takeda. All other authors have declared no conflicts of interest.

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    Targeted therapies and immunotherapies (ID 46)

    • Event: ELCC 2017
    • Type: Poster Discussion session
    • Track:
    • Presentations: 2
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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): J.C. Yang

      • 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.

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      93PD - Afatinib (A) vs gefitinib (G) in patients with EGFR mutation-positive (EGFRm+) NSCLC: Updated OS data from the phase IIb trial LUX-Lung 7 (LL7) (ID 301)

      14:45 - 15:45  |  Author(s): J.C. Yang

      • Abstract

      Background:
      A, an irreversible ErbB family blocker, and G, a reversible EGFR TKI, are approved for 1st-line treatment (tx) of advanced EGFRm+ NSCLC. In LL7, A (40 mg/d) significantly improved PFS (HR 0.73 [95% CI 0.57–0.95], p = 0.017), ORR (70 vs 56%, p = 0.008) and time to tx failure (TTF; HR 0.73 [0.58–0.92], p = 0.007) vs G (250 mg/d) in this setting; the primary OS analyses (data cut-off 8 Apr 16) showed a non-significant difference in OS between A and G (median 27.9 vs 24.5 mos; HR 0.86 [0.66–1.12], p = 0.258) that was consistent across subgroups. Here, we present updated OS data.

      Methods:
      LL7 assessed A vs G in tx-naïve pts with EGFRm+ (Del19/L858R) stage IIIb/IV NSCLC. Co-primary endpoints were PFS, TTF and OS. Other endpoints: ORR and AEs.

      Results:
      Data cut-off for the updated OS analysis was 12 Dec 16. Median follow-up for OS was 49.2 mos. 73/77% (A/G) of pts had ≥1 subsequent systemic anti-cancer tx after discontinuation of A/G. 48/56% (A/G) received a subsequent EGFR TKI; 31 (19%)/26 (16%) pts (A/G) received a 3[rd]-gen EGFR TKI. Updated median OS was 27.9 vs 24.5 mos with A vs G (HR 0.85 [0.66–1.09], p = 0.1950). Landmark 24-mo and 30-mo OS with A vs G was 61 vs 51% and 48 vs 40%, respectively; 48-mo OS was 28% with A vs 20% with G. In patients treated with A, ≥30-mo survival rates were generally similar across countries of origin and mean average dose received. Similar OS trends were observed with A vs G in pts with Del19 (30.7 vs 26.4 mos; HR 0.82 [0.59–1.15]) and L858R (25.0 vs 21.2 mos; HR 0.89 [0.61–1.31]) mutations. There was a trend towards improved OS with A vs G in pts who received a 3[rd]-gen EGFR TKI (NE vs 48.3 mos; HR 0.49 [0.20–1.19]). In patients treated with A, consistent OS outcomes were observed across age groups (median, mos: 28.9 [<60 years]; 30.1 [<65 years]; 28.9 [<75 years]; 27.9 [≥75 years]). Updated PFS, TTF and ORR (at primary OS data cut-off, 8 Apr 16) were similar to the primary analyses, and all were significantly improved with A vs G; the AE profile of A and G was virtually unchanged since the primary analysis.

      Conclusions:
      In this updated OS analysis, there was no significant difference in OS with A vs G. A trend favouring A, generally consistent across subgroups, was observed.

      Clinical trial identification:
      Clinical Trials.gov Identifier: NCT01466660

      Legal entity responsible for the study:
      Boehringer Ingelheim

      Funding:
      Boehringer Ingelheim

      Disclosure:
      K. Park: Participated on advisory boards for Astellas, AstraZeneca, Boehringer Ingelheim, Clovis Oncology, Eli Lilly, Hanmi, Merck & Co., Inc., 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, AZ. T. Mok: Receipt of grants/research supports: AstraZeneca, BI, Pfizer, Novartis, SFJ, Roche, MSD, Clovis Oncology, BMS. Receipt of honoraria or consultation fees: AstraZeneca, Roche/Genentech, Pfizer, Eli Lilly, BI, Merck Serono, MSD, Janssen, Clovis Oncology, BioMarin, GSK, Novartis, SFJ Pharmaceutical, ACEA Biosciences, Inc., Vertex Pharmaceuticals, BMS, AVEO & Biodesix, Prime Oncology, Amgen. Participation in a company sponsored speaker’s bureau: AstraZeneca, Roche/Genentech, Pfizer, Eli Lilly, BI, MSD, Amgen, Janssen, Clovis Oncology, GSK, Novartis, BMS, PrIME Oncology. Stock shareholder: Sanomics Limited. K. O\'Byrne: Ad board, speaker bureau, travel to international conferences and honoraria: AZ, BMS, Roche-Genentech, MSD, Pfizer, BI. Ad board and speaker bureau: Novartis. 3 Patents: 1 on novel drugs, 2 on biomarkers, IP held by Queensland University of Technology. V. Hirsh: Has received advisory board honoraria from Boehringer Ingelheim, AstraZeneca, Roche, Merck, Eli Lilly, Pfizer, Amgen, and Bristol-Myers Squibb. M. Boyer: Ad board: BMS, Merck Sharpe and Dohme, Pfizer Board of Directors: IASLC Research: Pfizer, Genentech, BI, AZ, Novartis, Merck Sharpe and Dohme, Clovis Honoraria: Merck Sharpe and Dohme, BI, BMS, AZ. J. Fan: Boehringer Ingelheim employee. All other authors have declared no conflicts of interest.