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David Planchard



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    Do we treat patients with I-O until progression? (ID 45)

    • Event: ELCC 2019
    • Type: Controversy session
    • Track:
    • Presentations: 1
    • Moderators:
    • Coordinates: 4/13/2019, 08:30 - 09:30, Room C
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      Second vote and conclusions (ID 111)

      08:30 - 09:30  |  Presenting Author(s): David Planchard

      • Abstract
      • Presentation
      • Slides

      Abstract not provided

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    ESMO Colloquium supported by Lilly Oncology in collaboration with MSD - How to best use immune checkpoint inhibitors in NSCLC: Single agents or combined with chemotherapy? (ID 56)

    • Event: ELCC 2019
    • Type: ESMO Colloquium
    • Track:
    • Presentations: 3
    • Moderators:
    • Coordinates: 4/10/2019, 04:45 - 06:15, Room A
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      Conclusion (ID 665)

      04:45 - 06:15  |  Presenting Author(s): David Planchard

      • Abstract

      Abstract not provided

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      Introduction (ID 660)

      04:45 - 06:15  |  Presenting Author(s): David Planchard

      • Abstract
      • Presentation

      Abstract not provided

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      Recommendation on second-line treatment according to first-line choice (ID 664)

      04:45 - 06:15  |  Presenting Author(s): David Planchard

      • Abstract
      • Presentation
      • Slides

      Abstract not provided

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    Lunch & Poster Display session (ID 58)

    • Event: ELCC 2019
    • Type: Poster Display session
    • Track:
    • Presentations: 3
    • Moderators:
    • Coordinates: 4/11/2019, 12:30 - 13:00, Hall 1
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      183TiP - A phase II study of [fam-] trastuzumab deruxtecan (DS-8201a) in HER2-overexpressing or -mutated advanced non-small cell lung cancer (ID 475)

      12:30 - 13:00  |  Presenting Author(s): David Planchard

      • Abstract
      • Slides

      Background

      Approximately 30% of non-small-cell lung cancers (NSCLC) are human epidermal growth factor receptor 2 (HER2)-overexpressing (immunohistochemistry [IHC] 2+ or 3+) and approximately 2% have HER2-activating mutations. However, no HER2-targeted therapies are approved for the treatment of NSCLC. [Fam-] trastuzumab deruxtecan (DS-8201a) is a novel HER2-targeted antibody-drug conjugate with a humanized HER2 antibody, a topoisomerase I inhibitor payload, cleavable peptide-based linker, and a high drug-to-antibody ratio of 7 to 8. In an ongoing phase 1 trial, [fam-] trastuzumab deruxtecan (6.4 mg/kg) had a confirmed objective response rate (ORR) of 58.8% (10/17) in HER2-expressing or -mutated NSCLC and 72.7% (8/11) in HER2-mutated NSCLC, with a manageable safety profile (Tsurutani et al, WCLC 2018).

      a9ded1e5ce5d75814730bb4caaf49419 Trial design

      This multicenter, open-label, 2-cohort, phase 2 study will assess the efficacy and safety of [fam-] trastuzumab deruxtecan (6.4 mg/kg once every 3 weeks) in HER2-overexpressing or -mutated unresectable and/or metastatic nonsquamous NSCLC that is relapsed/refractory to standard treatment or for which no standard treatment is available (NCT03505710). Approximately 80 subjects will be enrolled; 40 in each of 2 cohorts (cohort 1: HER2-overexpressing [IHC 3+ or IHC 2+]; cohort 2: HER2-mutated including exon 20 insertions and single-nucleotide variants in kinase, transmembrane, and extracellular domains [eg, L755S, V659E, S310F]). To be eligible for cohort 1, HER2-overexpression must be assessed and confirmed by central testing based on archival samples. To be eligible for cohort 2, any HER2-activating mutation must be documented based on archival tumor samples. Study treatment will be continued until progressive disease or unacceptable toxicity. The primary endpoint is ORR based on RECIST version 1.1 by an independent radiologic facility. Secondary efficacy endpoints include progression-free survival, duration of response, disease control rate, and overall survival. Safety assessments include serious and treatment-emergent adverse events. The study will enroll subjects in North America, Europe, and Japan. Recruitment began in May, 2018.

      d9b324a48b043b3d87bc9b3fe620f260 Clinical trial identification

      NCT03505710.

      7a6a3ffa2dadc03a6151ee2c4d6fa383 Editorial acknowledgement

      Editorial assistance was provided by Stefan Kolata, PhD, of AlphaBioCom, LLC.

      934ce5ff971f1ab29e840a35e3ca96e9 Legal entity responsible for the study

      Daiichi Sankyo, Inc.

      213f68309caaa4ccc14d5f99789640ad Funding

      Daiichi Sankyo, Inc.

      682889d0a1d3b50267a69346a750433d Disclosure

      D. Planchard: Member on the speakers program, Advisory board: AstraZeneca, Boehringer Ingelheim, BMS, Merck, Celgene, Novartis, Pfizer, Roche. R. Shiga, C.C. Lee, K. Wang: Full-time employee: Daiichi Sankyo. P.A. Jänne: Consulting fees, research funding: Acea, Astellas, AstraZeneca, Araxes, ARIAD, Boehringer Ingelheim, Chugai, Daiichi Sankyo, Eli Lilly, Ignyta, Loxo, Merrimack, Pfizer, PUMA, Genentech; Stock: Gatekeeper; Royalties: LabCorp. All other authors have declared no conflicts of interest.

      cffcb1a185b2d7d5c44e9dc785b6bb25

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      185TiP - RATIONALE 001: Tislelizumab (BGB-A317) + concurrent chemoradiotherapy (cCRT) followed by tislelizumab monotherapy in patients (pts) with newly diagnosed locally advanced, unresectable, stage III non-small cell lung cancer (NSCLC) (ID 252)

      12:30 - 13:00  |  Author(s): David Planchard

      • Abstract
      • Slides

      Background

      In pts with locally advanced, unresectable, stage III NSCLC, cCRT is associated with better survival than radiotherapy (RT) alone, but 5-y survival remains poor. Immunotherapies targeting PD-1/PD-L1 may be synergistic with cCRT, improving outcomes. Tislelizumab, an anti–PD-1 antibody, showed clinical activity/tolerability in solid tumors, including NSCLC. RATIONALE 001 is a phase III, randomized, double-blind, placebo-controlled trial evaluating the efficacy and safety of first-line tislelizumab + cCRT in pts with locally advanced, unresectable, stage III NSCLC.

      a9ded1e5ce5d75814730bb4caaf49419 Trial design

      RATIONALE 001 aims to answer important scientific questions by employing a 3-arm study design (840 pts randomized 1:1:1) to evaluate whether the timing of giving tislelizumab earlier upfront with cCRT in addition to consolidation will improve outcomes rather than giving the anti–PD-1 as consolidation only (Table). Both tislelizumab approaches (Arms 1 and 2) will each be compared to a global standard of care, cCRT alone. Chemotherapy will be investigator’s choice (cisplatin + etoposide or carboplatin + paclitaxel). RT will be given in 2 Gy fractions (target dose of 60 Gy). Key eligibility: Locally advanced, unresectable, stage III NSCLC; stage III confirmed by FDG-PET and brain imaging; Eastern Cooperative Oncology Group performance status ≤ 1; and no prior anti–PD-1/PD-L1 therapy. PD-L1 expression assessment is not required prior to randomization. Primary endpoint: Progression-free survival. Secondary endpoints include overall survival (OS), OS at 24 mo, objective response rate, and safety. Blood and tumor biomarkers, including PD-L1 expression and tumor mutational burden, will be evaluated for correlations with clinical benefit.

      d9b324a48b043b3d87bc9b3fe620f260 Clinical trial identification

      NCT03745222; EudraCT: 2018-001132-22.

      7a6a3ffa2dadc03a6151ee2c4d6fa383 Legal entity responsible for the study

      Celgene Corporation.

      213f68309caaa4ccc14d5f99789640ad Funding

      Celgene Corporation.

      682889d0a1d3b50267a69346a750433d Disclosure

      L. Paz-Ares: Honoraria: Lilly, MSD, BMS, Roche, Pharmamar, Merck, AstraZeneca, Novartis, Boehringer Ingelheim, Celgene, Servier, Sysmex, Celgene, Amgen, Incyte, Pfizer; Board member: Genomica; Institutional financial interest: AstraZeneca, BMS, MSD. S. Senan: Grants/Research support: Varian Medical Systems; Advisory/Board member: Celgene, AstraZeneca; Honoraria: Varian Medical Systems, AstraZeneca. D. Planchard: Consulting, honoraria, travel and/or institutional: AZ, BMS, BI, Celgene, Daiichi Sankyo, Eli Lilly, Merck, MedImmune, Novartis, Pfizer, prIME Onc, Peer CME, Roche; Institutional: Medimmune, Sanofi-Aventis, Taiho Pharma, Novocure, Daiichi Sankyo. A. Cheong: Employment, stock holder: Celgene Europe Ltd. R. Slepetis: Employment, stock holder: Celgene. M.H. Nguyen: Employment, stock holder: Celgene Corporation. E.E. Vokes: Employment: University of Chicago; Grants/Research support: AbbVie; Consultant, honoraria: AbbVie, Amgen, AstraZeneca, Biolumina, BMS, Celgene, Eli Lilly, EMD Serono, Genentech, Merck, Novartis, Regeneron. All other authors have declared no conflicts of interest.

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      23P - Immunosenescence (iSenescence) correlates with progression (PD) to PD-(L)1 inhibitors (IO) and not to platinum-chemotherapy (PCT) in advanced non-small cell lung cancer (aNSCLC) patients (pts) (ID 599)

      12:30 - 13:00  |  Author(s): David Planchard

      • Abstract

      Background

      iSenescence is a remodeling of immune functions with a multifactorial etiology (i.e. aging, chronic inflammation, cancer). Although the absence of CD28 and the expression of CD57 and KLRG1 on circulating T-lymphocytes are hallmarks of iSenescence, the characterization of such phenotype in aNSCLC pts and the correlation with clinical characteristics and benefit from IO or PCT are currently unknown.

      a9ded1e5ce5d75814730bb4caaf49419 Methods

      A senescent immune phenotype (SIP) defined as % of circulating CD8+CD28-CD57+KLRG1+ T-lymphocytes was assessed by flow cytometry (FC) on fresh blood from aNSCLC pts treated with IO or PCT in a single institution. A log-rank maximization method was used to identify a SIP cut-off level and dichotomize pts accordingly. The objective was to correlate SIP with clinical characteristics and RECIST response by univariate logistic regression analysis.

      20c51b5f4e9aeb5334c90ff072e6f928 Results

      37 aNSCLC pts were evaluable for SIP before IO: 32% ≥ 65 years, 91% non-squamous, 43% KRAS mutated, 51% with PD-L1 expression ≥1%, 8% chemotherapy naïve. 43% had PD, 41% stability (SD), 16% partial response (PR). Median PFS and OS were 2.7 (95% CI 1.8; 7.3) and 13 (95% CI 4.8-NR) months, respectively, median follow-up was 9.3 (95% CI 6.2-14.9) months. SIP (% CD28-CD57+KLRG1+) median value on circulating CD8+ lymphocytes was 12.2% (min 1.7%, max 56.1%). 32% of pts had >20.47% CD8+ lymphocytes with a CD28-CD57+KLRG1+ phenotype, being classified SIP+. SIP status did not significantly correlate with age, pts’ characteristics or CT exposure. 2 (17%) of 12 SIP+ had PR/SD (DCR), vs 19 (76%) of 25 SIP- pts (p = 0.001); median PFS was significantly lower in SIP+ (1.5 months 95% CI 1;2.2) vs SIP- pts (7.4 months 95% CI 5.5, 9.3) (p = 0.001). Among 61 aNSCLC pts treated with 1st line PCT, 18% had PD, 43% SD, 39% PR. SIP median value on circulating CD8+ lymphocytes was 17.9% (min 0.89%, max 66.1%), 43% of pts were SIP+. SIP did not significantly correlate with DCR (OR: 0.82, 95% CI 0.22-3.13, p = 0.82) upon PCT.

      fd69c5cf902969e6fb71d043085ddee6 Conclusions

      iSenescence, monitored by FC measurement of 3 surface molecules on circulating CD8 + lymphocytes, is observed in 32% and 43% of aNSCLC pts before IO or PCT, respectively. SIP correlated with lower DCR upon IO and not PCT.

      b651e8a99c4375feb982b7c2cad376e9 Legal entity responsible for the study

      Institut Gustave Roussy.

      213f68309caaa4ccc14d5f99789640ad Funding

      Has not received any funding.

      682889d0a1d3b50267a69346a750433d Disclosure

      All authors have declared no conflicts of interest.

      cffcb1a185b2d7d5c44e9dc785b6bb25

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    Mini Oral session I (ID 60)

    • Event: ELCC 2019
    • Type: Mini Oral session
    • Track:
    • Presentations: 1
    • Moderators:
    • Coordinates: 4/11/2019, 08:00 - 08:50, Room A
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      196O - STELLAR: Final updated results of a phase II trial of TTFields with chemotherapy for unresectable malignant pleural mesothelioma (ID 567)

      08:00 - 08:50  |  Author(s): David Planchard

      • Abstract
      • Presentation
      • Slides

      Background

      Tumor Treating Fields (TTFields), an anti-mitotic, regional treatment approved for glioblastoma utilizes low intensity, alternating electric fields delivered non-invasively to the tumor using a portable medical device. In-vitro, human mesothelioma cells were highly susceptible to TTFields.

      a9ded1e5ce5d75814730bb4caaf49419 Methods

      The trial accrued 80 patients with unresectable, previously untreated mesothelioma. Patients were treated with continuous 150 kHz TTFields (>18h/day) in combination with pemetrexed and cisplatin or carboplatin. Inclusion criteria included ECOG PS of 0-1 and pathologically proven mesothelioma. The primary endpoint was overall survival (OS). A visual analog scale was used to assess EOCG performance status and cancer-related pain assessed until disease progression. The sample size provided 80% power with two-sided alpha of 0.05 to detect an increase in median OS of 5.5 months compared to historical controls (Vogelzang, JCO 2003).

      20c51b5f4e9aeb5334c90ff072e6f928 Results

      All 80 patients had a minimum follow up of 12 months. Median age was 67 (range 27-78), 84% were male and 44% (35 patients) had an ECOG PS of 1. 66% (53 patients) had epithelioid histology, similar to the Vogelzang study. Median OS was 18.2 months (95% CI 12.1-25.8) versus 12.1 months in the historical control. Median OS for epithelioid patients was 21.2 months (95% CI 13.2-25.8). ECOG score was stable during the first year of follow up. Median time to deterioration in performance status was 13.1 months. Average score of pain was lower compared to baseline during the first 7 months of the treatment and was higher later on the study, with a median time to a clinical significant 33% increase in pain of 8.4 months. No device-related serious adverse events (AEs) were reported. Expected TTFields-related dermatitis was reported in 46% (37 patients). Four patients (5%) had grade 3 dermatitis.

      fd69c5cf902969e6fb71d043085ddee6 Conclusions

      The study met primary endpoint of significant extension of overall survival in previously untreated mesothelioma patients. TTFields was not associated with a decrease in performance status or an increase in pain for the duration of TTFields use. TTFields in combination with chemotherapy is efficacious in malignant pleural mesothelioma compared to historical data.

      b651e8a99c4375feb982b7c2cad376e9 Clinical trial identification

      NCT02397928.

      7a6a3ffa2dadc03a6151ee2c4d6fa383 Legal entity responsible for the study

      Novocure.

      213f68309caaa4ccc14d5f99789640ad Funding

      Novocure.

      682889d0a1d3b50267a69346a750433d Disclosure

      G.L. Ceresoli, F. Grosso: Travel funds: Novocure. All other authors have declared no conflicts of interest.

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    Mini Oral session II (ID 63)

    • Event: ELCC 2019
    • Type: Mini Oral session
    • Track:
    • Presentations: 1
    • Moderators:
    • Coordinates: 4/11/2019, 16:40 - 17:40, Room C
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      85O - Prevalence of programmed death ligand-1 (PD-L1) by demographic, disease and sample characteristics in unresectable, stage III NSCLC (PACIFIC) (ID 305)

      16:40 - 17:40  |  Presenting Author(s): David Planchard

      • Abstract
      • Presentation
      • Slides

      Background

      PACIFIC (NCT02125461) was a randomised, placebo-controlled, phase 3 trial evaluating the immune checkpoint inhibitor durvalumab in patients (pts) with unresectable, Stage III non-small cell lung cancer (NSCLC) who did not have disease progression after concurrent chemoradiotherapy (cCRT). Both primary endpoints of progression-free survival and overall survival were met and significantly improved with durvalumab, with similar safety, versus placebo (Antonia et al, NEJM 2017; 2018). We report exploratory analyses of the prevalence of tumour PD-L1 expression by baseline pt, disease and sample characteristics and by response to prior treatment for pts in PACIFIC.

      a9ded1e5ce5d75814730bb4caaf49419 Methods

      If available (provision of formalin-fixed paraffin-embedded tumour resection or biopsy samples was optional), archived pre-cCRT tumour tissue was tested retrospectively for PD-L1 tumour cell (TC) expression using the VENTANA PD-L1 (SP263) immunohistochemistry assay and scored at validated pre-specified (≥25%) and post-hoc (≥1%) cutoffs. Overall PD-L1 prevalence (regardless of treatment arm) was summarised by pt subgroups defined by various characteristics, and assessed using a Pearson’s chi-squared test for between-group differences.

      20c51b5f4e9aeb5334c90ff072e6f928 Results

      Of 713 randomized pts, 451 (63.2%) were evaluable for PD-L1 status. Among PD-L1-evaluable pts, 67.2% (303/451) had TC ≥ 1% and 35.3% (159/451) had TC ≥ 25% (similar to previous reports in metastatic NSCLC). PD-L1 prevalence by various characteristics at the TC ≥ 1% cut-off are reported in the table.

      fd69c5cf902969e6fb71d043085ddee6 Conclusions

      There were no important differences noted in PD-L1 prevalence between relevant subgroups at the TC ≥ 1% or TC ≥ 25% cut-offs (latter data to be presented). PD-L1 status was unaffected by sample type or age or biopsy location, suggesting expression is stable from pre-cCRT diagnostic biopsies, and supports the use of either primary tumour or lymph node biopsies for PD-L1 testing.

      b651e8a99c4375feb982b7c2cad376e9 Clinical trial identification

      NCT02125461.

      7a6a3ffa2dadc03a6151ee2c4d6fa383 Editorial acknowledgement

      Medical writing support, which was in accordance with Good Publication Practice (GPP3) guidelines, was provided by Andrew Gannon of Cirrus Communications, an Ashfield company, and was funded by AstraZeneca.

      934ce5ff971f1ab29e840a35e3ca96e9 Legal entity responsible for the study

      AstraZeneca.

      213f68309caaa4ccc14d5f99789640ad Funding

      AstraZeneca.

      682889d0a1d3b50267a69346a750433d Disclosure

      D. Planchard: Personal fees: AstraZeneca, Boehringer Ingelheim, BMS, MSD, Pfizer, Novartis, Roche, Celgene, outside the submitted work. M.C. Garassino: Personal fees: AstraZemeca, Roche, BMS, MSD outside the conduct of this study. L. Paz-Ares: Advisory board fees: BMS, Lilly, MSD, AstraZeneca, Roche, Pfizer, Novartis, Incyte, Merk, Boehringer Ingelheim. C. Faivre-Finn: Research funding:AstraZeneca, MSD. A. Spira: Advisory fees, institutional research support: AstraZeneca. Y. Gu, J. Whiteley, M. Scott, J. Walker: Employment, stock: AstraZeneca. C. Wadsworth, P.A. Dennis: Employment, stock: AstraZeneca, outside the conduct of the study. A-M. Boothman: Employment, stock options: AstraZeneca, outside the conduct of the study. M. Ratcliffe: Consultant fees: AstraZeneca, outside the conduct of the study. All other authors have declared no conflicts of interest.

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    NSCLC stage IV oncogenic addicted disease (ID 9)

    • Event: ELCC 2019
    • Type: Educational session
    • Track:
    • Presentations: 1
    • Moderators:
    • Coordinates: 4/10/2019, 16:30 - 18:00, Room B
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      Targeted therapy beyond EGFR, ALK and ROS1 (ID 22)

      16:30 - 18:00  |  Presenting Author(s): David Planchard

      • Abstract
      • Presentation
      • Slides

      Abstract not provided

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    Proffered Paper session I (ID 57)

    • Event: ELCC 2019
    • Type: Proffered Paper session
    • Track:
    • Presentations: 1
    • Moderators:
    • Coordinates: 4/10/2019, 16:30 - 18:15, Room C
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      LBA2 - Patient-reported outcomes (PROs) with durvalumab by PD-L1 expression in unresectable, stage III NSCLC (PACIFIC) (ID 308)

      16:30 - 18:15  |  Author(s): David Planchard

      • Abstract
      • Presentation
      • Slides

      Background

      In the ph 3 PACIFIC study of Stage III NSCLC pts without progression after cCRT, PFS and OS were significantly improved with durva vs. pbo, with no detrimental effect on PROs. We retrospectively investigated the impact of tumour PD-L1 expression on PROs.

      a9ded1e5ce5d75814730bb4caaf49419 Background

      In the phase 3 PACIFIC study of unresectable, Stage III NSCLC pts without progression after platinum-based concurrent chemoradiotherapy (cCRT), the primary endpoints PFS and OS were significantly improved with durvalumab versus placebo with similar safety and no detrimental effect on PROs. We retrospectively investigated the impact of tumour PD-L1 expression on PROs to better understand the benefit/risk profile of durvalumab across all PD-L1 subgroups.

      a9ded1e5ce5d75814730bb4caaf49419 Methods

      After ≥2 cCRT cycles, pts were randomised (2:1) to durva 10 mg/kg or pbo IV q2w up to 12 mo. If available, optional pre-cCRT tumour tissue was tested for PD-L1 tumour cell (TC) expression using the VENTANA SP263 immunohistochemistry assay and scored at pre-specified (25% or unknown) and post-hoc (1%) cutoffs. PROs were assessed using EORTC QLQ-C30 and -LC13 with changes from BL analysed by a mixed model for repeated measures, HRs for time to deterioration (TTD) by a stratified Cox proportional-hazards model, and ORs for improvement rates by logistic regression.

      20c51b5f4e9aeb5334c90ff072e6f928 Methods

      After cCRT with ≥2 chemotherapy cycles, pts were randomised (2:1) to durvalumab 10 mg/kg or placebo IV q2w up to 12 months. If available, optional pre-cCRT tumour tissue was tested for PD-L1 tumour cell (TC) expression using the VENTANA SP263 immunohistochemistry assay and scored at pre-specified (25%) and post-hoc (1%) cutoffs. PROs were assessed using EORTC QLQ-C30 and -LC13 with changes from baseline (BL) analysed by a mixed model for repeated measures, hazard ratios (HRs) for time to deterioration (TTD) by a Cox proportional-hazards model, and odd ratios (ORs) for improvement rates by logistic regression.

      20c51b5f4e9aeb5334c90ff072e6f928 Results

      Of 713 pts, 63% had known PD-L1 status. Compliance was high (>80% at Wk 48) across all five PD-L1 subgroups (TC ≥25%, <25%, ≥1%, <1%, and unknown). Most PROs remained stable; however, similar to the ITT population, clinically relevant improvements from BL to Wk 48 were observed for dysphagia and alopecia across most subgroups (4/5 and 5/5, respectively) for durva (mean changes 10.1−20.9 and 15.5−26.9) and all for pbo (10.4−19.4 and 15.8−31.3); plus improvements with pbo for TC ≥25% (12.5 for chest pain and constipation) and TC <25% (10.0 for appetite loss and arm/shoulder pain). Across most subgroups, there were no TTD differences, except those favouring durva: for TC ≥25%, chest pain (HR=0.57), physical functioning (0.60), emotional functioning (0.47), pain (0.56), and haemoptysis (0.42); and, similar to ITT, for TC ≥25%, <25%, ≥1% and <1%, ‘other pain’ (0.60, 0.57, 0.67 and 0.39, respectively). Improvement rates were also similar, except as follows, favouring durva: for TC ≥25%, role functioning (OR=2.84) and, similar to ITT, appetite loss (4.33); for TC ≥1%, diarrhoea (4.50) and haemoptysis (19.34); and, for TC<1%, ‘other pain’ (7.25); for TC<25%, the rate favoured pbo for cough (0.51).

      fd69c5cf902969e6fb71d043085ddee6 Results

      Of 713 pts, 63% had known PD-L1 status. Similar to the intent-to-treat (ITT) population, most PROs remained stable over time from BL across the PD-L1 subgroups (TC ≥25%, <25%, ≥1%, <1%, or unknown), with no clinically meaningful (CM) differences (≥10 points) for durvalumab compared to placebo. However, similar to the ITT population, CM improvements (decreases ≥10 points) from BL to Week 48 were observed for dysphagia and alopecia across most PD-L1 subgroups for both durvalumab (mean changes 8.1 [not CM]−20.9 and 15.5 − 26.9, respectively) and placebo (mean changes 10.4 − 19.4 and 15.8 − 31.3). Pre-specified and post hoc TTD analyses of PROs by PD-L1 subgroup were generally similar to those of the ITT population, with overlapping HR and 95% CIs. Similarly, PRO improvement rates by PD-L1 subgroup were generally similar to those of the ITT population, with overlapping OR and 95% CIs.

      fd69c5cf902969e6fb71d043085ddee6 Conclusions

      Similar to the ITT population, there were minimal between-Tx differences in PROs based on PD-L1 expression, supporting use of the PACIFIC regimen (durvalumab after cCRT) in all comers.

      b651e8a99c4375feb982b7c2cad376e9 Conclusions

      There were no CM differences in PROs between treatment arms across various PD-L1 subgroups. Results were generally consistent with those in the ITT population, suggesting that PD-L1 expression did not influence PROs in this study.

      b651e8a99c4375feb982b7c2cad376e9 Clinical trial identification

      NCT02125461

      7a6a3ffa2dadc03a6151ee2c4d6fa383 Editorial acknowledgement

      Medical writing support, which was in accordance with Good Publication Practice (GPP3) guidelines, was provided by Hashem Dbouk, PhD, of Cirrus Communications, an Ashfield company, and was funded by AstraZeneca.

      934ce5ff971f1ab29e840a35e3ca96e9 Editorial acknowledgement

      Medical writing support, which was in accordance with Good Publication Practice (GPP3) guidelines, was provided by Andrew Gannon of Cirrus Communications, an Ashfield company, and funded by AstraZeneca.

      934ce5ff971f1ab29e840a35e3ca96e9 Legal entity responsible for the study

      AstraZeneca.

      213f68309caaa4ccc14d5f99789640ad Funding

      AstraZeneca.

      682889d0a1d3b50267a69346a750433d Disclosure

      M.C. Garassino: Personal fees: AstraZeneca, Roche, BMS, MSD. L. Paz-Ares: Advisory fees: BMS, Lilly, MSD, AstraZeneca, Roche, Pfizer, Novartis, Incyte, Merck, Boehringer Ingelheim, outside the conduct of the study. C. Faivre-Finn: Research funding: AstraZeneca, MSD, outside the conduct of the study. A. Spira: Consultant fees, institutional research support: AstraZeneca, outside the conduct of the study. D. Planchard: Personal fees: AstraZeneca, Boehringer Ingelheim, BMS, MSD, Pfizer, Novartis, Roche, Celgene, outside the conduct of the study. M. Ozguroglu: Consultant fees: Astellas; Honoraria: Janssen, outside the conduct of the study. A. Rydén, P.A. Dennis: Employment, stock: AstraZeneca. Y. Zhang, C. O’Brien: Employment, stock: AstraZeneca, outside the conduct of the study. All other authors have declared no conflicts of interest.

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    Proffered Paper session II (ID 61)

    • Event: ELCC 2019
    • Type: Proffered Paper session
    • Track:
    • Presentations: 1
    • Moderators:
    • Coordinates: 4/11/2019, 09:00 - 10:30, Room A
    • +

      110O - Plasma circulating tumor DNA analysis (ctDNA) for molecular alteration detection in advanced non-small cell lung cancer (NSCLC) patients (pts) with isolated central nervous system (CNS) metastases (mts) (ID 310)

      09:00 - 10:30  |  Author(s): David Planchard

      • Abstract
      • Presentation
      • Slides

      Background

      In advanced NSCLC, ctDNA is an emerging tool in molecular profile testing at diagnosis and at resistance to targeted therapies. However, for CNS limited mts, ctDNA might have a reduced accuracy because of low concentrations. Aim: to assess feasibility of ctDNA in NSCLC with isolated CNS disease/progression (PD) (iCNS).

      a9ded1e5ce5d75814730bb4caaf49419 Methods

      This is a retrospective analysis of consecutive advanced NSCLC pts treated at Gustave Roussy from 01.2016 to 06.2018 included in 2 prospective studies (CEC-CTC, MSN). Included: any molecular tissue alteration at baseline (EGFR, ALK, BRAF, KRAS, HER2, ROS1, MET, TP53), CNS disease and ≥1 ctDNA sample at diagnosis/PD. CtDNA was performed by next generation sequencing (NGS- InVisionSeq™-Lung). Clinical/molecular/imaging data were collected. CtDNA in iCNS group were compared to systemic PD group (with CNS PD or stable disease, S-CNS). ctDNA was defined as positive if ≥ 1 mutation in the NGS panel.

      20c51b5f4e9aeb5334c90ff072e6f928 Results

      422/959 screened pts had ≥1 ctDNA sample. 183/422 pts had CNS disease. 58/182 pts had ctDNA sample at time of CNS disease and 66 samples were eligible for inclusion: 21 iCNS and 45 S-CNS (≥1 sample/patient as ≥ 1 PD). In iCNS and S-CNS, pts characteristics were: median age 55 vs 59 years, female gender 94% vs 59%, adenocarcinoma histology 100% vs 93%, smoking history 35% vs 44%, median mts sites at diagnosis 1 vs 2. Prevalence of EGFR mutation at diagnosis was 76 and 61%, ALK rearrangement 18 and 10%, KRAS 6 and 5% in iCNS and in S-CNS, respectively. HER2, TP53, BRAF and MET alterations were present only in S-CNS group (12%, 10%, 5% and 2%). CtDNA was positive in 38% in iCNS vs. 98% in S-CNS groups (Fisher test, p < 0.0001) (Table).

      fd69c5cf902969e6fb71d043085ddee6 Conclusions

      In NSCLC pts with isolated CNS involvement, genomic alterations assessed by ctDNA in plasma had a low detection rate. (Table).

      b651e8a99c4375feb982b7c2cad376e9 Legal entity responsible for the study

      Gustave Roussy Institute, Villejuif, France.

      213f68309caaa4ccc14d5f99789640ad Funding

      Has not received any funding.

      682889d0a1d3b50267a69346a750433d Disclosure

      L. Mezquita: Consulting, advisory role: Roche Diagnostics; Lectures, educational activities: Bristol-Myers Squibb, Tecnofarma, Roche, AstraZeneca; Travel, accommodations, expenses: Chugai. D. Planchard: Consulting, advisory role or lectures: AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Celgene, Daiichi Sankyo, Eli Lilly, Merck, Novartis, Pfizer, prIME Oncology, Peer CME, Roche; Honoraria: AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Celgene, Eli Lilly, Merck, Novartis, Pfizer, prIME Oncology, Peer CME, Roche; Clinical trials research: AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Eli Lilly, Merck, Novartis, Pfizer, Roche, Medimmun, Sanofi-Aventis, Taiho Pharma, Novocure, Daiichi Sankyo. C. Morris, E. Green: Employee, shareholder: Inivata. B. Besse: Sponsored research at Gustave Roussy Cancer Center: AbbVie, Amgen, AstraZeneca, Biogen, Blueprint Medicines, BMS, Celgene, Eli Lilly, GSK, Ignyta, IPSEN, Merck KGaA, MSD, Nektar, Onxeo, Pfizer, Pharma Mar, Sanofi, Spectrum Pharmaceuticals, Takeda, Tiziana Pharma; Investigator or co-investigator of trials: Nerviano, GSK, Pfizer, Roche-Genentech, Lilly, OSE Pharma, MSD, Celgene, Stemcentrx, Ignyta, AbbVie, Loxo Oncology, AstraZeneca, Blueprint Medicines. All other authors have declared no conflicts of interest.

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    Should sequencing of ALK inhibitors be molecularly-guided? (ID 51)

    • Event: ELCC 2019
    • Type: Controversy session
    • Track:
    • Presentations: 1
    • Moderators:
    • Coordinates: 4/12/2019, 17:45 - 18:45, Room A
    • +

      Second vote and conclusions (ID 126)

      17:45 - 18:45  |  Presenting Author(s): David Planchard

      • Abstract
      • Presentation
      • Slides

      Abstract not provided

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