Virtual Library

 x 
My Library Virtual Library FAQ

Start Your Search

L. Paz-Ares

Moderator of

  • +

    Immunotherapies and targeted therapies in advanced NSCLC (ID 39)

    • Event: ELCC 2017
    • Type: Proffered Paper session
    • Track:
    • Presentations: 6
    • +

      Invited Discussant 83O, 84O and 2O (ID 526)

      14:45 - 16:15  |  Author(s): L. Paz-Ares

      • Abstract
      • Presentation
      • Slides

      Abstract not provided

      Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.

      Only Active Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login or select "Add to Cart" and proceed to checkout.

    • +

      Invited Discussant 85O_PR (ID 528)

      14:45 - 16:15  |  Author(s): E. Smit

      • Abstract
      • Presentation
      • Slides

      Abstract not provided

      Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.

      Only Active Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login or select "Add to Cart" and proceed to checkout.

    • +

      2O - Favorable clinical outcome and response to immunotherapy share a common PD-L1/PD-1 based NSCLC immune contexture (ID 400)

      14:45 - 16:15  |  Author(s): G. Mazzaschi, D. Madeddu, G. Bocchialini, L. Gnetti, G. Armani, F. Sogni, M. Tiseo, A. Ardizzoni, F. Aversa, F. Quaini

      • Abstract
      • Presentation
      • Slides

      Background:
      The success of PD-1/PD-L1 immune checkpoint inhibitors strengthens the notion that tumor growth and regression are immune regulated. According to PD-L1 status and number of Tumor Infiltrating Lymphocytes (TILs), the cancer microenvironment can be classified into four types reflecting immune resistance, ignorance, induction and tolerance. However, an extended tissue characterization of the immune contexture and its predictive/prognostic value in NSCLC remain elusive. The aim of the present investigation was to determine whether immunologically defined classes of NSCLC differentially impact on clinical outcome.

      Methods:
      Histologic sections of NSCLC samples surgically removed to untreated 51 ADC and 69 SCC and 8 ADC and 10 SCC patients receiving Nivolumab were included. PD-L1 (clones 28-8 and SP142) was measured by immunoperoxidase (H-score) and immunofluorescence (QIF). The n/mm[2] and intra-, peri-tumor or invasive margin localization of TILs subpopulations were computed establishing cut off values relative to each phenotype. Immunohistochemical data and clinical records were subjected to Kaplan Meier analysis.

      Results:
      ADC cases had 2-fold higher CD3[pos] and 1.8-fold lower CD4[pos] cells compared to SCC and TILs-rich ADC had 10 months’ increase in OS vs –poor (p < 0.01). EGFR mutation conditioned a lower intratumor density of TILs. The frequency of type I (PD-L1[high] TILs[high]) contexture was low (14.6%) while > 1/3 of NSCLC samples displayed type II (PD-L1[low/neg] TILs[low]), reflecting immune exhaustion. The proportion of type III (PD-L1[high] TILs[low]) and IV (PD-L1[low/neg] TILs[high]) immune categories, with relatively increased Nks and Tregs, was similar. NSCLC type III had the highest OS (35.5 mos.) and PFS (25.7) while in type II immune ignorant cases OS and PFS were respectively 21.7 and 12. Independently from immune categories, patients with PD-1[low] and high CD8/CD3 ratio had 11 mos. gain in OS (p < 0.01) compared to the reverse counterpart. Accordingly, PD-L1[high] and PD-1[low] characterized 86% of patients responsive to nivolumab.

      Conclusions:
      In a dynamic PD-L1 milieu a concomitant intrinsic or therapeutically induced decay of PD-1 receptor allows TILs to escape from PD-L1 pressure and delays tumor progression, improving OS.

      Clinical trial identification:


      Legal entity responsible for the study:
      University Hospital of Parma, Medicine

      Funding:
      University of Parma

      Disclosure:
      All authors have declared no conflicts of interest.

      Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.

      Only Active Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login or select "Add to Cart" and proceed to checkout.

    • +

      83O - A phase II study of durvalumab (MEDI4736) for previously treated patients with stage IV squamous NSCLC (SqNSCLC): Lung-MAP Sub-study SWOG S1400A (ID 279)

      14:45 - 16:15  |  Author(s): V. Papadimitrakopoulou, M.W. Redman, H. Borghaei, S.N. Waqar, F. Robert, G.J. Kiefer, S. McDonough, R.S. Herbst, K. Kelly, D.R. Gandara

      • Abstract
      • Presentation
      • Slides

      Background:
      Durvalumab (MEDI4736) is an engineered human IgG1 mAb targeting programmed cell death ligand-1 (PD-L1). Treatment with other anti-PD-1/PD-L1 antibodies has demonstrated meaningful clinical benefit in patients with advanced NSCLC.

      Methods:
      As part of the Lung Master Protocol S1400, a National Clinical Trials Network group "umbrella" trial for second-line SqNSCLC we conducted a phase II study of durvalumab in patients with Stage IV squamous NSCLC (ECOG PS 0-2; ≥1 prior systemic treatment regimens, including one platinum-based), EGFR/ALK wild-type. The primary endpoint was overall response rate (ORR) (RECIST v1.1); secondary endpoints included duration of response (DoR), ORR among PD-L1 positive patients, disease control rate (DCR), investigator-assessed progression-free survival (PFS), overall survival (OS) and safety (CTCAE v4.03). The initial protocol was a randomized phase II/III comparison of durvalumab to docetaxel, and was amended to be a single arm phase II trial of single agent durvalumab. PD-L1 positive tumors were defined by ≥ 25% of tumor cells with membrane staining.

      Results:
      Of the 68 eligible patients (median [range] age 66 [35-92] years, PS 0/1/2 26%/62%/12%), 11 were responders (16% ORR, 95% Confidence Interval [CI] 7%, 25%). DCR was 54% (CI 43%, 66%), median OS was 11.5 months (CI 10.1-12.4 mos), and median PFS was 2.9 mos (CI 2.0-4.1 mos). Of the 11 responders, median time to response and DoR were 3.6 mos (CI 2.8-4.2 mos) and 18.6 months (95% CI 4.4-NR mos), respectively. Of the 14 PDL1-positive patients, 2 were responders (14% ORR, 95% CI 0%, 33%), DCR was 57% (CI 31%, 83%), median OS and PFS were 10.7 mos (CI 9.2-10.7 mos) and 2.3 mos (CI 1.4-4.9 mos), respectively. Durvalumab showed a manageable safety and tolerability profile; most adverse events (AEs) were low grade and resolved with treatment delay and/or immunosuppressive interventions. Grade ≥3 treatment-related AEs occurred in 23(34%) of patients. Drug-related AEs led to discontinuation in 6 patients (9%, 95% CI 2%, 16%).

      Conclusions:
      Durvalumab demonstrated clinical benefit and durable responses in a previously treated metastatic NSCLC population with manageable toxicity profile. Results are comparable with other anti-PD-1/PD-L1 therapies in metastatic, relapsed NSCLC.

      Clinical trial identification:
      NCT02766335

      Legal entity responsible for the study:
      Southwest Oncology Group/NCTN

      Funding:
      Lung-MAP supported in part by NIH/NCI grants CA180888, CA180819, CA180820, CA180821, CA180868, and by Amgen, AstraZeneca, Bristol-Myers Squibb Company Genentech and Pfizer through the Foundation for the National Institutes of Health, in partnership with Friends of Cancer Research.

      Disclosure:
      V. Papadimitrakopoulou: Advisory Role for: Eli Lilly&Co, Genentech, Janssen Global Sevices, Bristol-Myers Squibb, ARIAD, Astra Zeneca Pharmaceuticals, Novartis, Merck Corporate-sponsored research: Novartis, Astra Zeneca, Genentech, Merck, Janssen, ACEA, Bristol-Myers Squibb. H. Borghaei: Advisory: Bristol-Myers Squibb, Lilly, Genentech, Celgene, Pfizer, EMD-Serono, Boerhinger-Ingelheim, Trovagene, AstraZeneca, Research Support: Millenium, Merck, Celgene. K. Kelly: Advisory: Synta, AstraZeneca, Lilly, Clovis Oncology, ARIAD, Boehringer Ingelheim, Bristol-Myers Squibb, Genentech, G1 Therapeutics. Research: Millenium, Novartis, EMD Serono, Lilly, Genentech, Abbvie, Gilead, Celgene, Five Prime Therapeutics, Transgene. All other authors have declared no conflicts of interest.

      Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.

      Only Active Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login or select "Add to Cart" and proceed to checkout.

    • +

      84O - Atezolizumab as first-line (1L) therapy for advanced non-small cell lung cancer (NSCLC) in PD-L1–selected patients: Efficacy data from the BIRCH trial (ID 367)

      14:45 - 16:15  |  Author(s): S. Peters, E. Carcereny Costa, M.C. Garassino, D. Christoph, T. Kurata, J. Chaft, M.L. Johnson, S. Mocci, S.N. Gettinger, E. Felip

      • Abstract
      • Slides

      Background:
      Atezolizumab (atezo) inhibits binding of PD-L1 to its receptors, PD-1 and B7.1, restoring tumor-specific T-cell immunity and leaving the PD-L2/PD-1 interaction intact. This single-arm Phase II study (BIRCH; NCT02031458) was designed to evaluate atezo monotherapy in PD-L1–selected patients with advanced NSCLC. A previous analysis (median follow-up, 8.5 months) demonstrated clinical activity in chemotherapy-naive 1L and 2L+ PD-L1–selected patients. Here we present updated efficacy data for 1L patients.

      Methods:
      Eligible patients had PD-L1–selected advanced-stage NSCLC, with no prior chemotherapy or CNS metastases. PD-L1 was centrally evaluated using the VENTANA SP142 IHC assay. Enrolled patients expressed PD-L1 on ≥ 5% of tumor cells (TC) or tumor-infiltrating immune cells (IC), ie, TC2/3 or IC2/3. Those with EGFR mutation or ALK rearrangement must have had prior treatment with an appropriate TKI. Atezo was administered (1200 mg IV q3w) until radiographic disease progression or unacceptable toxicity. The primary endpoint was independent review facility (IRF)–assessed ORR; secondary endpoints included investigator (INV)-assessed ORR, DOR, PFS (RECIST v1.1) and OS.

      Results:
      With a median duration of survival follow-up of 22.5 months, INV-assessed ORR was 25% in TC2/3 or IC2/3 (all treated) patients and 34% in TC3 or IC3 patients (Table). Median OS was 23.5 months in all treated patients and 26.9 months in the TC3 or IC3 subgroup. Responses were observed in both EGFR and KRAS mutant and wild-type tumors. The safety profile was consistent with previous atezo NSCLC studies.

      Conclusions:
      With a median follow-up of 22.5 months, atezo continued to demonstrate durable clinical benefit in 1L NSCLC, in both EGFR and KRAS mutant and wild-type tumors. These results support ongoing Phase III trials evaluating atezo vs chemotherapy in 1L NSCLC.rnTable: 84Orn

      rnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrn
      Endpoint (95% CI)TC3 or IC3[a] (n = 65)TC2/3 or IC2/3[b] (n = 138)
      INV ORR, %34%25%
      (22.6-46.7)(18.4-33.5)
      EGFR mutant/wild type, ORR, %25%/31%31%/22%
      KRAS mutant/wild type, ORR, %38%/30%31%/22%
      Median DOR, moNE16.5
      (8.5-NE)(9.9-NE)
      Median OS, mo26.923.5
      (12.0-NE)(18.1-NE)
      12-mo OS rate, %61.5%66.4%
      (49.0-74.0)(58.1-74.6)
      Median PFS, mo7.37.3
      (4.9-12.0)(5.7-9.7)
      12-mo PFS rate, %36.5%32.5%
      (24.0-48.9)(24.2-40.8)
      rnNE, not estimable.rnaTC ≥ 50% or IC ≥ 10% PD-L1–expressing cells.rnbTC or IC ≥ 5% PD-L1–expressing cells.rn

      Clinical trial identification:
      NCT02031458

      Legal entity responsible for the study:
      F. Hoffmann-La Roche Ltd/Genentech Inc., a member of the Roche Group

      Funding:
      F. Hoffmann-La Roche Ltd/Genentech Inc, a member of the Roche Group

      Disclosure:
      M.C. Garassino: Honoraria, Consulting, Speaker\'s Bureau, research funding, expert testimony, travel expenses: MSD, BMS, AZ, Lilly, Roche. D. Christoph: Honoraria, Speaker\'s Bureau: BI, BMS, Chugai, Novartis, Merck, MSD, Pfizer, Roche; Consulting: BI, BMS, Novartis, Pfizer, Roche; Expert testimony: BI, BMS, Novartis, Pfizer, Roche. J. Chaft: Advisor for Genentech and Astra Zeneca. M.L. Johnson: Consulting: Genentech, Celgene, BI; Research funding: OncoMed, BerGenBio, Lilly, EMD Serono, Kadmon, Janssen, Mirati, Genmab, Pfizer, AZ, Roche/Genentech, Stemcentrix, Novartis, Checkpoint, Array, Regeneron. S. Mocci: Employee, stock: Roche/Genentech. S.N. Gettinger: Consulting: BMS; Research funding: Roche/Genentech, BMS, ARIAD, Incyte, Celldex. E. Felip: Advisory Boards: Lilly, Pfizer, BI, MSD, Roche; Speaker\'s Bureau: AZ, BMS, Novartis. All other authors have declared no conflicts of interest.

      Only Active Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login or select "Add to Cart" and proceed to checkout.

    • +

      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): C.K. Lee, S. Novello, A. Ryden, A. Templeton, K. Rüdell, H. Mann, S. Ghiorghiu, 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
      SymptomTreatmentNumber (%) of patients with eventHR (95% CI)p-value
      CoughO99 (46.0)0.74 (0.53, 1.05)0.090
      C58 (54.7)
      Chest painO99 (43.8)0.52 (0.37, 0.73)<0.001
      C66 (58.4)
      DyspnoeaO122 (53.5)0.42 (0.31, 0.58)<0.001
      C84 (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).

      Only Active Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login or select "Add to Cart" and proceed to checkout.

  • +

    Is there a role for second-line immunotherapy in patients with PD-L1 negative NSCLC? (ID 22)

    • Event: ELCC 2017
    • Type: Controversy session
    • Track:
    • Presentations: 4
    • +

      Introduction and first vote (ID 89)

      09:15 - 10:15  |  Author(s): M. Reck

      • Abstract
      • Slides

      Abstract not provided

      Only Active Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login or select "Add to Cart" and proceed to checkout.

    • +

      No (ID 91)

      09:15 - 10:15  |  Author(s): B. Besse

      • Abstract
      • Slides

      Abstract not provided

      Only Active Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login or select "Add to Cart" and proceed to checkout.

    • +

      Second vote and conclusions (ID 92)

      09:15 - 10:15  |  Author(s): L. Paz-Ares

      • Abstract
      • Slides

      Abstract not provided

      Only Active Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login or select "Add to Cart" and proceed to checkout.

    • +

      Yes (ID 90)

      09:15 - 10:15  |  Author(s): R. Herbst

      • Abstract
      • Presentation
      • Slides

      Abstract not provided

      Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.

      Only Active Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login or select "Add to Cart" and proceed to checkout.



Author of

  • +

    Immunotherapies and targeted therapies in advanced NSCLC (ID 39)

    • Event: ELCC 2017
    • Type: Proffered Paper session
    • Track:
    • Presentations: 1
    • +

      Invited Discussant 83O, 84O and 2O (ID 526)

      14:45 - 16:15  |  Author(s): L. Paz-Ares

      • Abstract
      • Presentation
      • Slides

      Abstract not provided

      Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.

      Only Active Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login or select "Add to Cart" and proceed to checkout.

  • +

    Industry Satellite Symposium 3 (ID 54)

    • Event: ELCC 2017
    • Type: Industry Satellite Symposium
    • Track:
    • Presentations: 2
    • Moderators:
    • Coordinates: 5/06/2017, 13:00 - 14:00, Room A
    • +

      Choices across treatment lines: Maximising patient outcomes in advanced or metastatic NSCLC (ID 569)

      13:00 - 14:00  |  Author(s): L. Paz-Ares

      • Abstract
      • Slides

      Abstract not provided

      Only Active Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login or select "Add to Cart" and proceed to checkout.

    • +

      Closing remarks (ID 575)

      13:00 - 14:00  |  Author(s): L. Paz-Ares

      • Abstract

      Abstract not provided

  • +

    Is there a role for second-line immunotherapy in patients with PD-L1 negative NSCLC? (ID 22)

    • Event: ELCC 2017
    • Type: Controversy session
    • Track:
    • Presentations: 1
    • +

      Second vote and conclusions (ID 92)

      09:15 - 10:15  |  Author(s): L. Paz-Ares

      • Abstract
      • Slides

      Abstract not provided

      Only Active Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login or select "Add to Cart" and proceed to checkout.

  • +

    Management of non-oncogene driven NSCLC (ID 11)

    • Event: ELCC 2017
    • Type: Specialty Session
    • Track:
    • Presentations: 1
    • +

      Anti-EGFR therapies in unselected NSCLC patients (ID 43)

      11:00 - 12:30  |  Author(s): L. Paz-Ares

      • Abstract
      • Presentation
      • Slides

      Abstract not provided

      Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.

      Only Active Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login or select "Add to Cart" and proceed to checkout.

  • +

    Poster Display Session (ID 63)

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

      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): L. Paz-Ares

      • 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.

    • +

      120P - Subgroup analysis of adenocarcinoma patients refractory to first-line chemotherapy from REVEL: A randomized phase III study of docetaxel with ramucirumab or placebo for second-line treatment of stage IV non–small cell lung cancer (NSCLC) (ID 423)

      12:30 - 13:00  |  Author(s): L. Paz-Ares

      • Abstract

      Background:
      In the phase III REVEL trial, ramucirumab plus docetaxel significantly improved median overall survival (OS), median progression-free survival (PFS), and objective response rate (ORR) in patients with advanced NSCLC who progressed after first-line platinum therapy, independent of histology. The REVEL trial also showed that ramucirumab plus docetaxel therapy improved median OS, median PFS, and ORR in adenocarcinoma patients who were refractory to first-line platinum therapy and in patients categorized as rapid progressors. Here, we report safety and quality of life (QoL) outcomes in refractory adenocarcinoma patients who participated in the REVEL trial.

      Methods:
      Patients were refractory if they had a best response of progressive disease to first-line treatment. Patients were randomized 1:1 to receive docetaxel 75 mg/m[2] in combination with either ramucirumab 10 mg/kg or placebo every 21 days until disease progression, unacceptable toxicity, or death. Treatment-emergent adverse events (TEAEs) were assessed according to the NCI-CTCAE, version 4.0. Quality of life was measured by the Lung Cancer Symptom Scale (LCSS).

      Results:
      Of the 1253 patients randomized (ramucirumab + docetaxel: 628; docetaxel + placebo: 625), 17% (ramucirumab + docetaxel: 9%; docetaxel + placebo: 8%) were adenocarcinoma patients refractory to first-line therapy. The safety overview and LCSS scores are presented in the table.rnTable: 120PSafety and QoL Outcomes of Refractory Adenocarcinoma Patients Treated in REVELrn

      rnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrn
      TEAEs, n (%)Ramucirumab + Docetaxel N = 111Placebo + Docetaxel N = 101
      Any TEAE108 (97)101 (100)
      Grade ≥3 TEAEs82 (74)73 (72)
      Serious TEAEs47 (42)48 (48)
      TEAEs leading to discontinuation6 (5)4 (4)
      TEAEs leading to death4 (4)11 (11)
      LCSS scores, time to deteriorationHazard Ratio (95% CI)
      Loss of appetite1.45 (0.91, 2.32)
      Fatigue0.90 (0.58, 1.41)
      Cough1.29 (0.77, 2.14)
      Dyspnea1.06 (0.64, 1.76)
      Hemoptysis1.55 (0.59, 4.07)
      Pain1.14 (0.71, 1.84)
      Symptom distress1.12 (0.69, 1.81)
      Activity level1.01 (0.64, 1.59)
      Global QoL0.98 (0.63, 1.52)
      Total LCSS0.81 (0.47, 1.41)
      ASBI0.83 (0.46, 1.50)
      rnNote: The primary LCSS analysis was time to deterioration, defined as the time from randomization to the first 15 mm increase. ASBI, average symptom burden index; CI, confidence interval; LCSS, Lung Cancer Symptom Scale; QoL, quality of life; TEAE, treatment-emergent adverse event.rn

      Conclusions:
      Our analysis did not identify any new safety concerns or increased detriment in QoL for this subgroup of patients. Safety outcomes for refractory adenocarcinoma patients were consistent with the outcomes for refractory patients with all histologies and the intent-to-treat population.

      Clinical trial identification:
      NCT01168973

      Legal entity responsible for the study:
      Eli Lilly and Company

      Funding:
      Eli Lilly and Company

      Disclosure:
      M. Reck: Personal fees from AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Eli Lilly and Company, Hoffmann-La Roche, Merck Sharp & Dohme, Novartis, and Pfizer. L. Paz-Ares: Personal fees from AMGEM, AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, CLOVIS, Eli Lilly and Company, Hoffmann-La Roche, Merck Sharp & Dohme, Novartis, and Pfizer. D. Moro-Sibilot: Personal fees from AMGEN, Ariad, AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Eli Lilly and Company, Hoffmann-La Roche, Merck Sharp & Dohme, Novartis, and Pfizer. F.A. Shepherd, M. Pérol: Personal fees from Eli Lilly and Company. F. Cappuzzo: Personal fees from AstraZeneca, Hoffmann-La Roche, and Pfizer. K.B. Winfree: Employee of Eli Lilly and Company and reports personal fees from Eli Lilly and Company. E. Alexandris: Employee of Eli Lilly and Company. A. Sashegyi, R. Varea: Employee and shareholder of Eli Lilly and Company.

    • +

      138TiP - An open-label phase 3b/4 safety trial of flat-dose nivolumab plus ipilimumab in patients with advanced non-small cell lung cancer (NSCLC) (ID 164)

      12:30 - 13:00  |  Author(s): L. Paz-Ares

      • Abstract

      Background:
      The combination of nivolumab and ipilimumab, immune checkpoint inhibitors with distinct but complementary mechanisms of action, is approved as first-line therapy for metastatic melanoma and has shown encouraging clinical activity in other tumors, including NSCLC. In CheckMate 012, a multi-cohort phase 1 trial in chemotherapy-naïve patients with NSCLC, nivolumab (3 mg/kg) plus ipilimumab (1 mg/kg) yielded objective response rates of up to 47%; discontinuation rates due to treatment-related adverse events were similar to those with nivolumab monotherapy. Data indicate comparable pharmacokinetic, safety, and efficacy profiles for 240 mg flat-dose nivolumab and 3 mg/kg nivolumab. This open-label phase 3b/4 study (ClinicalTrials.gov identifier: NCT02869789) will characterize the safety of flat-dose nivolumab plus ipilimumab in patients with advanced NSCLC. This study will also evaluate this combination in special patient populations who are typically excluded from NSCLC trials.

      Trial design:
      Adult patients with stage IV/recurrent NSCLC and no prior systemic anticancer therapy (cohort A; n = 400), or with stage IIIb/IV NSCLC and recurrence or progression during or after one prior platinum doublet chemotherapy regimen (cohort B; n = 400) will be enrolled. Patients are required to have assessment of programmed death-1 ligand 1 expression, Eastern Cooperative Oncology Group performance status (ECOG PS) 0–1, and no untreated brain metastases, carcinomatous meningitis, autoimmune disease, or active malignancy requiring concurrent intervention. A third cohort (A1; n = ∼200) with no prior systemic therapy will have ECOG PS 2 or one or more of the following: asymptomatic untreated brain metastases, renal or hepatic dysfunction, and/or HIV. All patients will receive flat-dose nivolumab (240 mg every 2 weeks) plus weight-based ipilimumab (1 mg/kg every 6 weeks). Endpoints are shown in the table.rnTable: 138 TiPStudy endpointsrn

      rnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrn rnrn
      PrimarySecondary
      Number and percentage of patients with high-grade treatment-related select and immune-mediated adverse eventsProgression-free survival
      Objective response rate
      Duration of response
      Patient-reported outcomes based on the Functional Assessment of Cancer Therapy-Lung (FACT-L)
      rn

      Clinical trial identification:
      NCT02869789

      Legal entity responsible for the study:
      Bristol-Myers Squibb

      Funding:
      Bristol-Myers Squibb

      Disclosure:
      L. Paz-Ares: Medical advisor for: Lilly, Roche, MSD, BMS, Celgene, Pfizer, Boehringer Ingelheim, Bayer, Clovis, and Astra Zeneca. C. Chakmakjian: Speaker\'s Bureau for: BMS. N. Ready: Honoraria from: BMS, Merck; Consultant for: BMS, Merck, Novartis, Abbvie. W. Hu, L. Krug, J. Fairchild: Bristol-Myers Squibb employee. All other authors have declared no conflicts of interest.

    • +

      144TiP - CheckMate 227: A randomized, open-label phase 3 trial of nivolumab, nivolumab plus ipilimumab, or nivolumab plus chemotherapy versus chemotherapy in chemotherapy-naïve patients with advanced non-small cell lung cancer (NSCLC) (ID 394)

      12:30 - 13:00  |  Author(s): L. Paz-Ares

      • Abstract

      Background:
      Platinum-based chemotherapy is standard-of-care first-line therapy for most patients with advanced NSCLC, but the clinical benefit is modest. Although first-line nivolumab, an immune checkpoint inhibitor antibody, did not improve progression-free survival or overall survival (OS) versus chemotherapy in patients with advanced NSCLC and ≥5% programmed death-1 ligand 1 (PD-L1) expression, OS compared favorably with historical controls of first-line platinum-based chemotherapy. Combining nivolumab with chemotherapy in this setting may increase the durability of tumor responses and broaden the population of patients to derive benefit. In a multi-cohort phase 1 study (CheckMate 012) in chemotherapy-naïve patients with advanced NSCLC, nivolumab plus chemotherapy had promising clinical activity, regardless of tumor PD-L1 expression, and a manageable safety profile. CheckMate 227 is a 2-part, randomized, open-label phase 3 trial (NCT02477826), evaluating first-line nivolumab, nivolumab plus ipilimumab, or nivolumab plus chemotherapy versus chemotherapy in patients with advanced NSCLC.

      Trial design:
      Part 1 of CheckMate 227, which has completed accrual, enrolled adult patients with stage IV/recurrent NSCLC, no prior systemic anticancer therapy, and assessment of PD-L1 expression at screening. Patients with ≥1% PD-L1 expression were randomized 1:1:1 to nivolumab, nivolumab plus ipilimumab, or chemotherapy arms; those with <1% PD-L1 expression were randomized 1:1:1 to nivolumab plus ipilimumab, nivolumab plus chemotherapy, or chemotherapy arms. In part 2, ∼480 previously untreated patients with advanced NSCLC, regardless of PD-L1 expression level, will be randomized 1:1 to receive histology-based platinum doublet chemotherapy alone or in combination with nivolumab. Part 2 of CheckMate 227, which is the focus of this presentation, allows for the evaluation of first-line nivolumab plus chemotherapy in a broad group of patients with advanced NSCLC across the PD-L1–expressing continuum.

      Clinical trial identification:
      NCT02477826

      Legal entity responsible for the study:
      Bristol-Myers Squibb

      Funding:
      Bristol-Myers Squibb

      Disclosure:
      L. Paz-Ares: Served as a medical advisor for the following companies: Lilly, Roche, MSD, BMS, Celgene, Pfizer, Boehringer-Ingelheim, Bayer, Clovis, and AstraZeneca. J. Brahmer: Received research grants and served as an uncompensated advisory board member for Bristol-Myers Squibb. M.D. Hellmann: Received grants from Genentech and Bristol-Myers Squibb. Received personal fees from Genentech, Bristol-Myers Squibb, Merck, AstraZeneca, Novartis, and Janssen. M. Reck: Received consultant fees and served on speaker\'s bureau for the following companies: Roche, Lilly, Bristol-Myers Squibb, MSD, AstraZeneca, Pfizer, Boehringer-Ingelheim, and Celgene. K. O\'Byrne: Received honoraria, speaker bureau and/or travel and registration support for national and international meetings from BMS, Boehringer-Ingelheim, Astrazeneca, Lilly Oncology, Novartis, MSD, Roche-Genentech and Pfizer. H. Borghaei: The institution has a clinical trial agreement w/BMS. Consultant/advisory board member for: BMS, Lilly, Genentech, Celgene, EMD-Serono, Merck, Pfizer, Trovagene, Millenium, & Boehringer-Ingelheim. Received grants from: Millenium, Merck, & Celgene. W.J. Geese, H. Lu: BMS Employee and stock holder. F.E. Nathan: BMS employee. S. Ramalingam: Served on ad hoc scientific advisory board meetings the following companies: Astra Zeneca, BMS, Boehringer Ingelheim, Celgene, Ariad, Amgen, Lilly, Merck, Genentech. Also received honoraria from BMS.

    • +

      71TiP - A randomized, phase 3 trial with anti-PD-1 monoclonal antibody pembrolizumab (MK-3475) versus placebo for patients with early stage NSCLC after resection and completion of standard adjuvant therapy (EORTC/ETOP 1416-PEARLS) (ID 399)

      12:30 - 13:00  |  Author(s): L. Paz-Ares

      • Abstract

      Background:
      In the last 5 years no major advances have been made in the treatment of early stage NSCLC. Checkpoint inhibitors have shown promising clinical efficacy in advanced, refractory non-small cell lung cancer (NSCLC), but they have not yet been explored in the adjuvant setting. PEARLS (NCT02504372) is international, triple-blinded, placebo-controlled, randomized phase III trial to compare pembrolizumab versus placebo after complete resection of stage IB (T ≥ 4 cm), II and IIIA NSCLC, followed by standard adjuvant chemotherapy, if appropriate as per local guidelines, in patients who have signed the informed consent.

      Trial design:
      Eligible patients are those with completely resected stage IB (T ≥ 4 cm), II and IIIA NSCLC that have or have not received adjuvant platinum-based chemotherapy and whose PD-L1 status is known: negative (TPS=0%) versus weak positive (TPS = 1-49%) versus strong positive (TPS≥50%). Co-primary endpoints are disease-free survival in the PD-L1 strong positive subgroup and in the overall population. An HR = 0.78 is targeted for the whole population with 640 disease free survival events from a sample size of 1380 randomized patients. Secondary endpoints include disease-free survival in the PD-L1 positive subgroup, overall survival in each subpopulation and in the overall population, lung cancer specific survival, and safety and tolerability. The exploratory endpoints will assess pharmacokinetics, immunogenicity, quality of life and potential biomarkers of treatment response. Recruitment started in January 2016 and is currently ongoing. As of November 17, 2016, among the 102 randomized patients so far, 44 (43.1%), 32 (31.4%) and 26 (25.5%) patients have negative, weak positive and strong positive PD-L1 status respectively.

      Clinical trial identification:
      (EudraCT number 2015-000575-27) (NCT02504372)

      Legal entity responsible for the study:
      MSD EORTC, ETOP

      Funding:
      MSD

      Disclosure:
      All authors have declared no conflicts of interest.

  • +

    Targeted therapies and immunotherapies (ID 46)

    • Event: ELCC 2017
    • Type: Poster Discussion session
    • Track:
    • Presentations: 2
    • +

      90PD - Previously treated advanced NSCLC cohort from a multi-disease phase 1 study of ramucirumab (R) plus pembrolizumab (P): Efficacy and safety data (ID 169)

      14:45 - 15:45  |  Author(s): L. Paz-Ares

      • Abstract

      Background:
      R (anti-VEGFR2) and P (anti-PD-1) are active in previously treated advanced NSCLC. Median progression-free survival (PFS) reported in KEYNOTE-001 (previously treated; PD-L1 all comers) was 3.0 months (95%CI, 2.2-4.0) and ORR was 18%. This is the first study to combine R with P.

      Methods:
      Ongoing, multi-cohort, phase 1a/b trial enrolled pts with confirmed NSCLC with prior progression on systemic therapy, measurable disease, ECOG PS 0-1 and baseline tumor tissue. PD-L1 was classified strongly positive (tumor proportion score [TPS] ≥50%), weakly positive (TPS=1-49%), or negative (TPS <1%) using the DAKO PD-L1 22C3 IHC pharmDx assay. Primary objective- assess safety and tolerability of R + P; preliminary efficacy will be examined.

      Results:
      As of 21-Nov-2016, 27 pts with previously treated advanced NSCLC received R at 10 mg/kg on Day 1 with P 200 mg on Day 1 q3W. Median age was 65, 78% male, 96% had a history of smoking, 78% had adenocarcinoma and 15% had squamous-cell carcinoma. Sixteen (59%) pts received ≥2 and 4 (15%) received ≥3 prior treatment regimens for their disease. Median duration of treatment was 7.0 mo (IQR 3.0-12.4) and 8.3 mo (IQR 3.3-12.4) for R and P, respectively. Treatment related adverse events (TRAEs) occurred in 25 (93%) pts, most commonly hypertension (26%) and asthenia (19%). Five (19%) pts experienced grade 3 TRAEs (adrenal insufficiency, delirium, hypertension [n = 2], hyponatremia, infusion related reaction, proteinuria, and respiratory failure). No grade 4-5 TRAEs occurred. ORR was 30% with a median time to response of 2.1 mo. Duration of response has not been reached. Responses occurred in PD-L1 unknown (n = 1), negative (n = 2), and strong positive (n = 5) groups as well as both histologies. Median PFS was 9.7 mo (95% CI 4.6-11.5) and overall survival rate at 6 mo was 84.9%. Disease control rate was 85%. Ten (37%) pts remain on study treatment, including all responders.

      Conclusions:
      R + P demonstrated encouraging antitumor activity independent of PD-L1 and histology. The safety profile was consistent with monotherapy treatment for each drug, with no additive toxicities. The study was amended and is now enrolling pts with treatment naïve advanced NSCLC.

      Clinical trial identification:
      NCT02443324 JVDF

      Legal entity responsible for the study:
      Eli Lilly and Company, Indianapolis, IN

      Funding:
      Eli Lilly and Company, Indianapolis, IN

      Disclosure:
      R.S. Herbst: Personal fees from Eli Lilly, outside the submitted work. E. Calvo: Institutional research funding: multiple- available upon request; Travel expenses: Lilly, PsiOxus, Novartis; Consultant: Novartis, GSK, Astellas, Genentech, Lilly, Nanobiotich, Pfizer; SB: Novartis. N. Isambert: Honoraria: Pfizer, Novartis; Consulting/Advisory: Merck Serono. J. Bendell: Institutional research funding: From multiple and available upon request, including Lilly and Merck. P. Cassier: Personal fees from Roche/Genentech, Novartis, Astra-Zeneca, Amgen, Plexxikon; non-financial support from Roche/Genentech, Merck Sharp Dohme, Astra-Zeneca, Plexxikon; and grants from Merck Sharp Dohme and Astra-Zeneca, outside the submitted work. J. Jin, G. Mi, J. Rege: Employee and stock holder at Eli Lilly and Company. L. Paz-Ares: Consultant/Advisory role: Roche, Lilly, Novartis, MSD, BMS, Amgen, Clovis, AZ, BI, Pfizer. All other authors have declared no conflicts of interest.

    • +

      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): L. Paz-Ares

      • 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.