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V. Papadimitrakopoulou



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    Immunotherapies and targeted therapies in advanced NSCLC (ID 39)

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

      • 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.

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    Targeted therapies and immunotherapies (ID 46)

    • Event: ELCC 2017
    • Type: Poster Discussion session
    • Track:
    • Presentations: 1
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      94PD - Adverse events self-reported by patients with advanced non-small cell lung cancer treated with osimertinib or chemotherapy (ID 353)

      14:45 - 15:45  |  Author(s): V. Papadimitrakopoulou

      • Abstract

      Background:
      The Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) complements standard adverse event (AE) reporting in oncology trials. We assessed patient-reported symptomatic AEs in individuals receiving osimertinib 80mg once daily or chemotherapy for advanced non-small cell lung cancer (NSCLC) in the AURA3 trial, using the PRO-CTCAE.

      Methods:
      AURA3 (NCT02151981) was a multinational, open-label, randomized phase III trial involving 419 patients.1 As part of exploratory analyses, individuals for whom validated local language versions were available (in English, German, Japanese or Spanish) were asked to complete the PRO-CTCAE by e-device, weekly for 18 weeks and then every 3 weeks.

      Results:
      In total, 161 patients (38%; 102 osimertinib, 59 chemotherapy) provided data for PRO-CTCAE analysis (mean age: 64 years; 63% women). The number of patients providing PRO-CTCAE data fluctuated between different items and time points, and decreased over the study period. Of patients on osimertinib providing information on acne/pimples, 37%, 38%, 32% and 29% reported having acne/pimples at baseline, 4 weeks, 12 weeks and 24 weeks, respectively, compared with 30%, 19%, 14% and 12% on chemotherapy. Most cases (>90%) were mild. Reported rates of diarrhoea changed little over time post-baseline and were higher with osimertinib than with chemotherapy (32% vs 36% at baseline, 47% vs 28% at 4 weeks, 53% vs 33% at 12 weeks, 45% vs 21% at 24 weeks). Most cases were mild or moderate. Fatigue (64% vs 72% at baseline, 72% vs 89% at 4 weeks, 55% vs 89% at 12 weeks, 60% vs 79% at 24 weeks) and decrease in appetite (54% vs 53% at baseline, 42% vs 75% at 4 weeks, 35% vs 69% at 12 weeks, 33% vs 46% at 24 weeks) were reported less commonly with osimertinib than with chemotherapy. Most cases were mild.

      Conclusions:
      Self-reported data from patients with NSCLC treated with osimertinib or chemotherapy showed changes over time in AE rates from start of treatment and differences in prevalence of patient-reported AEs (PRO-CTCAEs) with osimertinib versus chemotherapy.

      Clinical trial identification:
      NCT02151981

      Legal entity responsible for the study:
      AstraZeneca

      Funding:
      AstraZeneca

      Disclosure:
      M. Sebastian: Honoraria: Novartis, BMS, Roche, Lilly, Boehringer-Ingelheim, Pierre-Fabre, Pfizer, MSD, AstraZeneca. Consultant: Novartis, BMS, Roche, Lilly, Boehringer-Ingelheim, Pfizer, MSD, AstraZeneca, Celgene. V. Papadimitrakopoulou: Advisory: Eli Lilly&Co, Genentech, Janssen Global Sevices, Bristol-Myers Squibb, ARIAD, AstraZeneca Pharmaceuticals, Novartis, Merck Corporate-sponsored. Research: Novartis, AstraZeneca, Genentech, Merck, Janssen, ACEA, Bristol-Myers Squibb. A. Walding: AstraZeneca employee and shareholder. S. Ghiorghiu: AstraZeneca employee and shareholder. A. Ryden: AstraZeneca employee and shareholder. K. Rudell: Former AstraZeneca employee and shareholder. All other authors have declared no conflicts of interest.