Author of

• 20039

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  Poster Display Session (ID 63)

  • Event: ELCC 2017
  • Type: Poster Display Session
  • Track:
  • Presentations: 1
  • Moderators:
  • Coordinates: 5/07/2017, 12:30 - 13:00, Hall 1

  • 19856

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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): V. Hirsh
    • 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.
    
    

• 20050

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  Targeted therapies and immunotherapies (ID 46)

  • Event: ELCC 2017
  • Type: Poster Discussion session
  • Track:
  • Presentations: 1
  • Moderators:S. Ekman, N. Reguart
  • Coordinates: 5/07/2017, 14:45 - 15:45, Room W

  • 20057

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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): V. Hirsh
    • 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.