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N. Leighl



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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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      139PD - Patient-reported outcomes from FLAURA: Osimertinib versus standard of care (SoC) epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) in patients with EGFR-mutated advanced non-small cell lung cancer (NSCLC) (ID 396)

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

      • Abstract
      • Slides

      Background:
      In the phase 3 FLAURA trial (N = 556), osimertinib demonstrated superior efficacy to SoC EGFR-TKI as first-line treatment of EGFR mutation-positive advanced NSCLC.[1]

      Methods:
      Patients in FLAURA completed the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 items (QLQ-C30) at baseline and then every 6 weeks, and Lung Cancer 13 items (QLQ-LC13) at baseline, then weekly for 6 weeks followed by every 3 weeks. Scores range from 0 to 100; higher scores represent greater symptom burden. A ≥10-point difference is considered clinically relevant. Pre-specified key symptoms were cough, dyspnoea, chest pain, appetite loss and fatigue.

      Results:
      Compliance with completing the questionnaire was ≥60% at all time points in both treatment arms. Baseline mean scores were similar in the osimertinib and SoC arms for cough (32.8 vs 33.5), dyspnoea (22.5 vs 25.0), chest pain (19.5 vs 20.8), appetite loss (22.7 vs 25.6) and fatigue (32.2 vs 35.8). Key symptoms improved in both arms from baseline over the first 9 months, with no significant differences in least-squares mean changes between the osimertinib and SoC arm (Table). Improvements in cough were seen from week 1 and were maintained throughout the first 9 months in both arms. QLQ-C30 functional and global health/quality of life scores improved from baseline in both arms, with no clinically relevant differences. Additional analyses are ongoing, including statistical significance testing and time to deterioration.Table:Change from baseline over 9 months in key patient-reported symptoms

      SymptomTreatmentnAdjusted least-squares mean (95% CI)Estimated treatment difference (95% CI)
      CoughOsimertinib248–11.0 (–12.8, –9.2)0.7 (–1.9, 3.2)
      SoC252–11.7 (–13.5, –9.8)
      DyspnoeaOsimertinib248–4.0 (–5.6, –2.5)0.1 (–2.2, 2.4)
      SoC252–4.1 (–5.7, –2.5)
      Chest painOsimertinib248–6.6 (–8.2, –5.0)–0.2 (–2.5, 2.1)
      SoC252–6.4 (–8.0, –4.8)
      Appetite lossOsimertinib252–6.2 (–8.4, –3.9)–0.5 (–3.7, 2.7)
      SoC247–5.6 (–8.0, –3.3)
      FatigueOsimertinib252–5.5 (–7.5, –3.5)–0.8 (–3.6, 2.1)
      SoC247–4.7 (–6.7, –2.7)
      Adjusted mean and estimated treatment differences obtained from a mixed-effects model for repeated measures. Model included patient (as a random effect), treatment, visit (as fixed effect and repeated measure), and treatment-by-visit interaction as explanatory variables, and the baseline symptom score as a covariate along with the baseline symptom score by visit interaction. The covariance structure for repeated measurements within the same patient was specified as unstructured. CI, confidence interval.

      Conclusions:
      Key patient-reported symptoms in the FLAURA trial improved in both treatment arms from baseline over 9 months. Improvements in cough in the two arms were clinically relevant. [1]Soria JC et al. N Engl J Med doi: 10.1056/NEJMoa1713137.

      Clinical trial identification:
      NCT02296125

      Legal entity responsible for the study:
      AstraZeneca

      Funding:
      AstraZeneca

      Disclosure:
      N. Leighl: Research funding to University Health Network in 2015 - unrelated. Honoraria for unrelated CME from: BMS, AZ, Pfizer, Roche. K. Nakagawa: MSD K.K., A2 Healthcare Corp., in Ventiv Health Japan, Astellas Pharma Inc., Daiichi Sankyo Co., Ltd., Novartis Pharma K.K., AbbVie Inc., Quintiles Inc., Icon Japan K.K., Chugai Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co., Ltd., EP-CRSU Co., Ltd., Gritstone Oncology. Inc, Linical Co., Ltd., Eli Lilly Japan K.K., Eisai Co., Ltd., Bristol Myers Squibb Company, Taiho Pharmaceutical Co., Ltd., PAREXEL International Corp., Ono Pharmaceutical Co., Ltd. for Research Funding AstraZeneca K.K., Nichi-Iko Pharmaceutical Co., Ltd., Astellas Pharma Inc. Clinical Trial Co., Ltd, MSD K.K., Taiho Pharmaceutical Co., Ltd., Ono Pharmaceutical Co., Ltd., Bristol Myers Squibb Company, Nippon Boehringer Ingelheim Co., Ltd., Eli Lilly Japan K.K., Novartis Pharma K.K., SymBio Pharmaceuticals Limited., Pfizer Japan Inc. for Honoraria Astellas Pharma Inc., Ono Pharmaceutical Co., Ltd. for Consulting or advisor role. J.E. Gray: Advisor to Astra Zeneca. T. Hovey: Working as a consultant (Phastar Statistician) for AstraZeneca. A. Walding: Employee and shareholder of AstraZeneca R&D. A. Rydén: Employee of AstraZeneca and has AstraZeneca stocks. S. Novello: Speaker bureau: Eli Lilly, AZ, BMS, MSD, Roche. All other authors have declared no conflicts of interest.

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    Poster Display session (Friday) (ID 65)

    • Event: ELCC 2018
    • Type: Poster Display session
    • Track:
    • Presentations: 1
    • Moderators:
    • Coordinates: 4/13/2018, 12:30 - 13:00, Hall 1
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      81P - The influence of comorbidity on health utility score (HUS) and health-related quality of life (HRQoL) in small cell lung cancer (SCLC) compared to non-small cell lung cancer (NSCLC) (ID 531)

      12:30 - 13:00  |  Author(s): N. Leighl

      • Abstract

      Background:
      A significant number of patients with SCLC suffer from comorbidities. In particular, heart failure and chronic obstructive pulmonary disease are often present. Comorbidity alone has been validated as an independent negative survival prognostic factor in SCLC. Despite this, comorbidities are rarely systematically assessed in relation to quality of life. Here, we examine the effect of comorbidity on HUS and quality of life in SCLC in relation to NSCLC.

      Methods:
      Histologically confirmed SCLC or NSCLC, were recruited from the Princess Margaret Cancer Centre. Demographics, treatment toxicity, and Patient Reported Charlson Comorbidity Index (PRO-CCI) were collected. For statistical analysis, univariable linear regression was applied to evaluate each variable and its association with HUS. A multivariable model with a backwards selection algorithm of univariable factors associated with HUS was employed.

      Results:
      Comorbidiity differentially drives HUS in SCLC compared to NSCLC (interaction p < 0.0001) and is an independent negative predictor of HRQoL (Table). Specifically, heart failure and COPD were two main modulators in SCLC quality of life (p < 0.05). Other prognostic factors, notably treatment-related symptom severity and performance status at diagnosis, did not differentially modulate HUS (Table). SCLC patients had a significantly higher number of comorbidities and lower HUS relative to NSCLC; nonetheless, comorbidity had the greatest magnitude of inverse relationship with HUS.

      Interaction TermsInteraction p-valueSCLCNSCLC
      CCI<0.0001−0.09 (−0.01, −0.06)−0.02 (−0.05, 0.01)
      Average severity of symptoms0.70−0.04 (−0.06, −0.02)−0.04 (−0.05, −0.02)
      Performance status at diagnosis0.53−0.06 (−0.11, −0.02)−0.08 (−0.12, −0.05)


      Conclusions:
      Comorbidity differentially modulates HUS in SCLC compared to NSCLC and is an important criterion to evaluate prior to treatment. We suspect that extensive smoking histories in the SCLC population may be driving these differential effects on HUS (Table). Interactions between factors differentially modulating HUS in SCLC and NSCLC.

      Clinical trial identification:


      Legal entity responsible for the study:
      Princess Margaret Hospital (University Health Network)

      Funding:
      Has not received any funding

      Disclosure:
      All authors have declared no conflicts of interest.