Author of

• 19946

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  Immunotherapies and targeted therapies in advanced NSCLC (ID 39)

  • Event: ELCC 2017
  • Type: Proffered Paper session
  • Track:
  • Presentations: 1
  • Moderators:L. Paz-Ares, N. Reguart
  • Coordinates: 5/06/2017, 14:45 - 16:15, Room B

  • 19951

    +

    85O_PR - Patient-reported symptoms and impact of treatment with osimertinib vs chemotherapy for advanced non-small cell lung cancer (ID 373)

    14:45 - 16:15  |  Author(s): T. Mok
    • Abstract
    • Slides

    Background:
    We assessed self-reported symptoms of advanced non-small cell lung cancer patients treated with osimertinib 80mg or chemotherapy in the AURA3 phase III clinical trial (NCT02151981).
    
    Methods:
    Patients completed the European Organisation for Research and Treatment of Cancer QLQ-LC13 questionnaire on disease-specific symptoms and QLQ-C30 on general cancer symptoms, functioning and global health status. QLQ-LC13 was completed at baseline, weekly for 6 weeks, then 3-weekly up to end of study, and at progression. QLQ-C30 was completed at baseline, then 6-weekly up to end of study, and at progression. We compared for differences between treatments in time to deterioration and odds of improvement of symptoms (two assessments ≥18 days apart). A deterioration or improvement was defined as a change in score from baseline of ≥ +/-10. Hazard ratios (HR) and 95% confidence intervals (CI) were calculated using a log-rank test stratified by ethnicity. Odds ratios (OR) and 95% CIs were calculated using logistic regression adjusted for ethnicity.
    
    Results:
    At baseline, 215 − 228 of 279 (77 − 82%) patients on osimertinib and 106 − 114 of 140 (76 − 81%) on chemotherapy had QLQ-LC13 scores ≤90 (cut-off to have potential for deterioration) for cough, chest pain and dyspnoea. Time to deterioration of key symptoms was longer with osimertinib than with chemotherapy (Table). The proportion of patients with improvement in global health status was higher with osimertinib (80/215 [37%]) than with chemotherapy (23/105 [22%]; OR: 2.11; 95% CI: 1.24, 3.67; p = 0.007), as it was for appetite loss (OR: 2.50; 95% CI: 1.31, 4.84) and fatigue (OR: 1.96; 95% CI: 1.20, 3.22).rnTable: 85O_PRTime to deterioration of selected key symptomsrn

    rnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrn rnrn

    Symptom	Treatment	Number (%) of patients with event	HR (95% CI)	p-value
    Cough	O	99 (46.0)	0.74 (0.53, 1.05)	0.090
    	C	58 (54.7)
    Chest pain	O	99 (43.8)	0.52 (0.37, 0.73)	<0.001
    	C	66 (58.4)
    Dyspnoea	O	122 (53.5)	0.42 (0.31, 0.58)	<0.001
    	C	84 (73.7)

    rnC, chemotherapy; O, osimertinib.rn
    
    Conclusions:
    Time to deterioration of key symptoms was longer and more patients had an improvement in global health status with osimertinib treatment than with chemotherapy, demonstrating improved patient outcomes with osimertinib.
    
    Clinical trial identification:
    NCT02151981
    
    Legal entity responsible for the study:
    AstraZeneca
    
    Funding:
    AstraZeneca
    
    Disclosure:
    C.K. Lee: Served on advisory boards for AstraZeneca. S. Novello: Served on speaker bureaux for AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Eli Lilly, Merck Sharp & Dohme Limited and Roche. A. Rydén, H. Mann, S. Ghiorghiu: Employees of AstraZeneca and are AstraZeneca shareholders. A. Templeton, K. Rüdell: Former employees of AstraZeneca and former shareholders. T. 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; 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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• 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): T. Mok
    • 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

  +

  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

    +

    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): T. Mok
    • 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.