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N. Pavlakis



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    Immunotherapy and next-generation TKIs: From second to frontline treatment (ID 55)

    • Event: ELCC 2018
    • Type: Poster Discussion session
    • Track:
    • Presentations: 1
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      138PD_PR - Patient-reported outcomes (PROs) in ALEX: A phase III study of alectinib (ALEC) vs crizotinib (CRIZ) in non-small-cell lung cancer (NSCLC) (ID 464)

      07:45 - 09:00  |  Author(s): N. Pavlakis

      • Abstract
      • Slides

      Background:
      ALEC showed superior efficacy versus CRIZ in patients (pts) with treatment-naïve ALK+ NSCLC in the phase III ALEX trial (NCT02075840). PRO data (disease burden, symptom tolerability and health-related quality of life [HRQoL]) are reported here.

      Methods:
      Pts (n = 303) were randomised 1:1 to receive ALEC (600 mg BID) or CRIZ (250 mg BID). Primary endpoint: investigator-assessed PFS. PROs were collected using EORTC QLQ-C30/QLQ-LC13 questionnaires. Pre-specified endpoints: time-to-deterioration (TTD) in lung cancer symptoms and HRQoL, longitudinal analyses of mean score changes from baseline, and proportion of pts with clinically meaningful change (≥10-point change from baseline) during treatment in the ITT population and patients with baseline CNS metastases.

      Results:
      Baseline completion rates and characteristics were balanced between arms in the PRO-evaluable population (ALEC n = 100, 65.8%; CRIZ n = 97, 64.2%). Median TTD in composite symptom endpoint (cough, dyspnoea, chest pain) was similar between arms (HR 1.10 [95% CI 0.72–1.68]). On average, ALEC pts reported a clinically meaningful improvement in baseline lung cancer symptoms for a longer duration of time versus CRIZ (cough, week 96 vs week 84; chest pain, week 96 vs week 80; fatigue, week 96 vs 68; pain in other parts, week 96 vs 68, respectively). Differences in lung symptoms between treatment arms tended to favour ALEC from 11.1 months (45 weeks), which was around the time of median PFS with CRIZ. ALEC pts reported a clinically meaningful improvement from baseline in HRQoL for a longer duration of time than CRIZ pts (week 88 vs 68, respectively). Fewer ALEC pts experienced a clinically meaningful worsening in treatment-related symptoms (nausea/vomiting, diarrhoea, appetite loss, dysphagia, peripheral neuropathy) than CRIZ pts.

      Conclusions:
      TTD for lung cancer symptoms was comparable between arms. Clinically meaningful improvement in lung cancer symptoms was maintained for longer with ALEC versus CRIZ, consistent with the improved PFS with ALEC versus CRIZ. HRQoL was improved with ALEC versus CRIZ. PRO data are consistent with ALEX safety data and confirm greater tolerability with ALEC versus CRIZ.

      Clinical trial identification:
      BO28984; 15 April 2016

      Legal entity responsible for the study:
      F. Hoffmann-La Roche Ltd

      Funding:
      F. Hoffmann-La Roche Ltd

      Disclosure:
      M. Perol: Advisory role for Roche and Pfizer. S. Peters: Education grants, provided consultation, attended advisory boards and/or provided lectures for the following organisations: Amgen, AstraZeneca, Boehringer-Ingelheim, Bristol-Myers Squibb, Clovis, Eli Lilly, F. Hoffmann-La Roche, Janssen, Merck Sharp and Dohme and Merck Serono, Pfizer, Regeneron and Takeda. N. Pavlakis: Advisory role for Novartis, Takeda, Roche and Pfizer. S. Novello: Speakers Bureau for: Eli Lilly, BMS, MSD, F. Hoffmann-La Roche Ltd and Astra Zeneca. T. Karagiannis: Employee of, owns stocks in and has taken part in company-sponsored research for Genentech. A. Zeaiter: Employee of F.Hoffman-La Roche Ltd. R. Dziadziuszko: Substantive relationships with Novartis, Pfizer and BMS. All other authors have declared no conflicts of interest.

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    New approaches in rare thoracic tumors (ID 60)

    • Event: ELCC 2018
    • Type: Proffered Paper session
    • Track:
    • Presentations: 1
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      213O - Nintedanib + pemetrexed/cisplatin in malignant pleural mesothelioma (MPM): Phase II biomarker data from the LUME Meso study (ID 206)

      11:00 - 12:30  |  Presenting Author(s): N. Pavlakis

      • Abstract
      • Presentation
      • Slides

      Background:
      The randomised Phase II/III LUME-Meso study is evaluating nintedanib + pemetrexed/cisplatin versus placebo + pemetrexed/cisplatin (≤6 cycles), followed by nintedanib or placebo maintenance, in chemo-naïve MPM. In the Phase II part, nintedanib treatment led to improved progression-free survival (PFS; hazard ratio [HR] = 0.54; p = 0.010) and a trend for longer overall survival (OS; HR = 0.77; p = 0.319) compared with placebo. Patients with epithelioid tumours derived greatest benefit. Plasma angiogenic factors and genomic markers were explored for potential associations with treatment outcome in the Phase II epithelioid population.

      Methods:
      Baseline plasma levels of 58 angiogenic factors were analysed by multiplex immunoassay (Human AngiogenesisMAP®, Myriad RBM). Genes implicated in the nintedanib mode of action and/or mesothelioma pathophysiology (VEGFR1, VEGFR3 and mesothelin) were evaluated for known single-nucleotide polymorphisms (SNPs). Biomarker associations with PFS/OS treatment effects were analysed by Cox regression and interaction tests with false-discovery rate (FDR) adjustment. Analyses were exploratory and hypothesis generating.

      Results:
      Angiogenic factor and genomic data were available for 71 and 67 patients, respectively, in the epithelioid population (n = 77). Of the angiogenic factors evaluated, only endoglin showed a possible trend for association with both PFS and OS improvement, with potentially greater benefit in patients with low plasma levels. Major homozygous genotypes for two VEGFR3 SNPs (rs307821 G/G and rs307826 A/A) showed weak association with OS effect, while the VEGFR1 SNP rs9582036 A/A genotype was potentially correlated with PFS benefit. However, all biomarker treatment associations were limited by small subgroup size (especially for minor genotypes) and FDR-adjusted interaction tests were not significant.

      Conclusions:
      These first biomarker results for nintedanib-treated MPM showed potential signals for greater PFS/OS benefits in patients with low plasma endoglin and major homozygous VEGFR1/3 genotypes, but no biomarkers showed clear and significant association with nintedanib efficacy.

      Clinical trial identification:
      NCT01907100

      Legal entity responsible for the study:
      Boehringer Ingelheim

      Funding:
      Boehringer Ingelheim

      Disclosure:
      N. Pavlakis: Advisory Boards: Boehringer Ingelheim, MSD, Merck, BMS, Astra Zeneca, Takeda, Bayer, Novartis, Pfizer, Roche, Ipsen Speaking Honoraria: Boehringer Ingelheim, Bayer, Novartis, Pfizer, Roche Travel Support: BMS, Astra Zeneca, Roche. N. Steele: Honoraria: Pfizer, Novartis Consulting/advisory role: MSD, Boehringer Ingelheim, BMS Research funding: Merck Serono, AstraZeneca, Boehringer Ingelheim, BMS, Novartis, Roche Travel, accommodation, expenses: Pfizer, MSD Oncology, Boehringer Ingelheim. A. Nowak: Consulting/ Advisory Role: Aduro Biotech, Morphotek, Bayer, AstraZeneca, Sellas Life Sciences, Trizell, Boehringer Ingelheim, Epizyme, Roche Research Funding: Boehringer Ingelheim, AstraZeneca Travel and expenses: Amgen, AstraZeneca, Boehringer Ingelheim. S. Novello: Speakers’ Bureau: AstraZeneca, MSD, Bristol-Myers Squibb, Roche, Pfizer, Eli Lilly. S. Popat: Honoraria: Pfizer, Boehringer Ingelheim, Eli Lilly, AstraZeneca, Novartis, Roche Consulting/advisory role: Boehringer Ingelheim, Eli Lilly, Pfizer, Novartis, Roche Research funding: Boehringer Ingelheim, Epizyme, BMS, Clovis Oncology, Eli Lilly, Roche. L. Greillier: Honoraria: Boehringer Ingelheim, Bristol-Myers Squibb, Eli Lilly, Pfizer, AstraZeneca, Novartis Pharma, Roche Consulting/advisory role: Boehringer Ingelheim, Bristol-Myers Squibb, Roche Research funding: Roche. M. Reck: Honoraria: Boehringer Ingelheim, Proacta, BMS, MSD, Pfizer, Eli Lilly, AstraZeneca, Merck Inc., Celgene, Novartis Consulting/advisory role: Boehringer Ingelheim, Eli Lilly, BMS, MSD, Pfizer, AstraZeneca, Merck Inc., Celgene, Novartis, Roche Speaker's bureau: Roche, Eli Lilly, MSD Oncology, Merck, AstraZeneca, BMS, Boehringer Ingelheim, Celgene, Pfizer, Novartis. T. Kitzing: Employment: Boehringer Ingelheim. G. Scagliotti: Honoraria: Eli Lilly, Pfizer, MSD, AstraZeneca, Roche Consulting/Advisory role: Eli Lilly Speakers’ Bureau: Eli Lilly, MSD. All other authors have declared no conflicts of interest.

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