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A. Rydén
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ESMO-IASLC Best Abstracts (ID 61)
- Event: ELCC 2018
- Type: Best Abstract session
- Track:
- Presentations: 1
- Moderators:M. Perol, L. Paz-Ares
- Coordinates: 4/13/2018, 16:45 - 18:30, Room B
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233O - Time to deterioration of symptoms with durvalumab in stage III, locally advanced, unresectable NSCLC: Post-hoc analysis of PACIFIC patient-reported outcomes (ID 703)
16:45 - 18:30 | Author(s): A. Rydén
- Abstract
- Presentation
Background:
Along with improving efficacy outcomes such as progression-free survival (PFS) after concurrent chemoradiotherapy (cCRT) in locally advanced, unresectable NSCLC, it is critical that new therapies are well tolerated in the curative intent setting. We studied the impact of 12 mo of durvalumab on disease symptoms in this setting using patient-reported outcomes (PROs). In a post-hoc analysis of time to deterioration, we adjusted for transient symptom changes by requiring two consecutive deterioration recordings.
Methods:
Patients whose disease did not progress after ≥2 cycles of platinum-based cCRT were randomised 2:1 1–42 days post-cCRT to durvalumab 10 mg/kg i.v. or placebo every 2 weeks for up to 12 mo/progression. Co-primary endpoints were PFS and overall survival. PROs were assessed using EORTC QLQ-C30 v3 and QLQ-LC13. Time to deterioration was defined as time from randomisation until the first clinically relevant deterioration (≥10 point change); in the post-hoc analysis, deterioration confirmation was required at the next time point. Hazard ratios (HR) and 95% confidence intervals (CIs) were estimated using a stratified Cox proportional-hazards model.
Results:
In the pre-specified analysis, there was no difference between treatment arms in time to deterioration besides other pain, which favoured durvalumab vs placebo (HR 0.72; 95% CI 0.58–0.89). Our post-hoc analysis indicated notable delays in deterioration of overall pain (HR 0.75; 95% CI 0.60–0.93), chest pain (HR 0.74; 95% CI 0.57–0.97), arm/shoulder pain (HR 0.74; 95% CI 0.58–0.95), nausea/vomiting (HR 0.72; 95% CI 0.54–0.97), insomnia (HR 0.75; 95% CI 0.58–0.97) and haemoptysis (HR 0.70; 95% CI 0.50–0.99) in favour of durvalumab, with no between-group differences for other items.
Conclusions:
PACIFIC primary analysis showed that durvalumab significantly improved PFS vs placebo (16.8 mo vs 5.6 mo, respectively) in the post-cCRT setting, and was well tolerated, largely without PRO deterioration. Our post-hoc analysis indicates a delay in several PROs with durvalumab not observed in the pre-specified analysis. Confirmation of worsening may provide a more precise picture of deterioration than one time point alone.
Clinical trial identification:
NCT02125461 (April 25, 2014)
Legal entity responsible for the study:
AstraZeneca PLC
Funding:
AstraZeneca
Disclosure:
R. Hui: Personal fees from the following: AstraZeneca, Merck Sharp and Dohme: Advisory Board Member and Speaker Honorarium; Novartis, Pfizer: Advisory Board Member; BMS, Boehringer Ingelheim: Speaker Honorarium. A. Villegas: Celgene, Alexion, BMS: Speaker's Bureau. A. Ryden, Y. Zhang, P. Dennis: AstraZeneca: full-time employment and stock ownership. S. Antonia: Moffitt Cancer Center: Full-time employment, Grants/research support; Novartis: Grants/research support, Advisory board, Honorarium recipient; BMS, Merck, Boehringer Ingelheim, AstraZeneca, Memgen: Advisory board, Honorarium recipient; CBMG: Advisory board, Stock/shareholder, Honorarium recipient. All other authors have declared no conflicts of interest.
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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
- Moderators:P. Garrido Lopez, S. Ekman, S. Ortiz-Cuaran, E. Wauters
- Coordinates: 4/12/2018, 07:45 - 09:00, Room A
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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 | Author(s): A. Rydén
- Abstract
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
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.Symptom Treatment n Adjusted least-squares mean (95% CI) Estimated treatment difference (95% CI) Cough Osimertinib 248 –11.0 (–12.8, –9.2) 0.7 (–1.9, 3.2) SoC 252 –11.7 (–13.5, –9.8) Dyspnoea Osimertinib 248 –4.0 (–5.6, –2.5) 0.1 (–2.2, 2.4) SoC 252 –4.1 (–5.7, –2.5) Chest pain Osimertinib 248 –6.6 (–8.2, –5.0) –0.2 (–2.5, 2.1) SoC 252 –6.4 (–8.0, –4.8) Appetite loss Osimertinib 252 –6.2 (–8.4, –3.9) –0.5 (–3.7, 2.7) SoC 247 –5.6 (–8.0, –3.3) Fatigue Osimertinib 252 –5.5 (–7.5, –3.5) –0.8 (–3.6, 2.1) SoC 247 –4.7 (–6.7, –2.7)
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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80P - Understanding the patient perspective of small cell lung cancer (SCLC) (ID 265)
12:30 - 13:00 | Presenting Author(s): A. Rydén
- Abstract
Background:
When developing a patient-reported outcomes assessment strategy, empirical evidence based on literature review and therapeutic area experts should be complemented with input directly from patients to reliably reflect the patients’ experiences. Therefore, a set of research activities were initiated to identify, describe, and substantiate concepts that reflect the important and relevant symptoms, treatment-related side effects, and impacts of extensive stage (ES)-SCLC.
Methods:
Twenty-five articles were reviewed, four clinical experts participated in advice meetings and 17 US patients diagnosed with ES-SCLC were interviewed. Trained interviewers used a semi-structured interview guide to elicit information from patients. Interviews were transcribed, coded, and analysed using qualitative data analytic methods.
Results:
Patients’ mean age was 65.2 years (SD = 9.8) and patients self-reported as white (n = 11, 64.7%), black or African American (n = 5, 29.4%), and American Indian or Alaska Native (n = 1, 5.9%). Thirty-one signs/symptoms of ES-SCLC were elicited with fatigue being mentioned by most patients (n = 10). Also, the most frequently reported SCLC symptoms were shortness of breath (n = 6, 35.3%), pain (n = 5, 29.4%), and weight loss (n = 4, 23.5%). Patients also reported numerous ways that their lives were impacted by ES-SCLC (n = 68 concepts), and treatment-related side-effects they experienced (n = 41 concepts). These findings, along with evidence from literature review and clinical experts, showed that shortness of breath, pain, weight loss, cough, fatigue, nausea, paraneoplastic syndromes, haemoptysis, and loss of appetite were reported as signs and symptoms of SCLC in all three research activities.
Conclusions:
This study provides an overview of symptoms, treatment-related side effects, and impacts associated with ES-SCLC from the patient perspective. The results suggest that patients with SCLC have similar key symptoms to patients with non-small cell lung cancer, therefore similar measurement strategies can be applied. Using this evidence, recommendations can be made for ES-SCLC clinical trial outcomes that resonate with primary stakeholders including patients, healthcare providers, regulatory agencies, and payers.
Clinical trial identification:
Not applicable.
Legal entity responsible for the study:
AstraZeneca PLC
Funding:
AstraZeneca
Disclosure:
A. Rydén, H. Jiang, P. Dennis: AstraZeneca: full-time employment and stock ownership. S. Ollis, E. Love, A.L. Shields: Employee of Adelphi Values, which receives payment from pharmaceutical companies to conduct outcomes-based research.
