Natasha B Leighl1, Nina Karaseva2, Kazuhiko Nakagawa3, Byoung-Chul Cho4, Jhanelle E Gray5, Tina Hovey6, Andrew Walding7, Anna Rydén8, Silvia Novello9. 1. Princess Margaret Cancer Centre, Toronto, ON, Canada. 2. City Clinical Oncology Dispensary, St. Petersburg, Russia. 3. Department of Medical Oncology, Kindai University Faculty of Medicine, Osakasayama, Japan. 4. Division of Medical Oncology, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Republic of Korea. 5. Department of Thoracic Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA. 6. PHASTAR, London, UK. 7. AstraZeneca R&D, Cambridge, UK. 8. AstraZeneca Gothenburg, Mölndal, Sweden. 9. Department of Oncology, University of Turin, Azienda Ospedaliero-Universitaria San Luigi Gonzaga, Turin, Italy. Electronic address: silvia.novello@unito.it.
Abstract
BACKGROUND: In the FLAURA trial, osimertinib demonstrated superior progression-free survival and a favorable toxicity profile to erlotinib or gefitinib as initial therapy in patients with EGFR-mutated advanced non-small-cell lung cancer. Patient-reported outcomes from FLAURA are discussed here. METHODS: Patients (N = 556) completed the EORTC QLQ-LC13 weekly for 6 weeks, then every 3 weeks, and the QLQ-C30 every 6 weeks. Prespecified key symptoms were cough, dyspnea, chest pain, appetite loss, and fatigue. Score changes from baseline to randomized treatment discontinuation were assessed using a mixed-effects model. A ≥10-point change was considered clinically relevant. Odds of improvement and time to deterioration were investigated. QLQ-C30 functioning scores were assessed post hoc. RESULTS: Questionnaire completion rates were >70% at most time points. Baseline mean scores were similar in the osimertinib and erlotinib/gefitinib arms. Scores improved in both arms, but none reached clinical relevance at 5% significance level. A statistically significant difference favoring osimertinib for chest pain was not clinically relevant (-6.84 vs -3.88; p = 0.021). Odds of improvement and time to deterioration were similar between treatments. In post hoc analyses, improvements favored osimertinib for emotional functioning (8.79 vs 4.91; p = 0.004) and social functioning (7.66 vs 1.74; p < 0.001). Cognitive functioning remained stable with osimertinib but deteriorated with erlotinib/gefitinib (0.03 vs -3.91; p = 0.005). CONCLUSIONS: Key symptoms improved from baseline in both treatment arms in FLAURA. Key symptom improvements that were both statistically significant and clinically relevant were not observed in favor of either treatment arm. CLINICAL TRIAL REGISTRATION: NCT02296125.
BACKGROUND: In the FLAURA trial, osimertinib demonstrated superior progression-free survival and a favorable toxicity profile to erlotinib or gefitinib as initial therapy in patients with EGFR-mutated advanced non-small-cell lung cancer. Patient-reported outcomes from FLAURA are discussed here. METHODS: Patients (N = 556) completed the EORTC QLQ-LC13 weekly for 6 weeks, then every 3 weeks, and the QLQ-C30 every 6 weeks. Prespecified key symptoms were cough, dyspnea, chest pain, appetite loss, and fatigue. Score changes from baseline to randomized treatment discontinuation were assessed using a mixed-effects model. A ≥10-point change was considered clinically relevant. Odds of improvement and time to deterioration were investigated. QLQ-C30 functioning scores were assessed post hoc. RESULTS: Questionnaire completion rates were >70% at most time points. Baseline mean scores were similar in the osimertinib and erlotinib/gefitinib arms. Scores improved in both arms, but none reached clinical relevance at 5% significance level. A statistically significant difference favoring osimertinib for chest pain was not clinically relevant (-6.84 vs -3.88; p = 0.021). Odds of improvement and time to deterioration were similar between treatments. In post hoc analyses, improvements favored osimertinib for emotional functioning (8.79 vs 4.91; p = 0.004) and social functioning (7.66 vs 1.74; p < 0.001). Cognitive functioning remained stable with osimertinib but deteriorated with erlotinib/gefitinib (0.03 vs -3.91; p = 0.005). CONCLUSIONS: Key symptoms improved from baseline in both treatment arms in FLAURA. Key symptom improvements that were both statistically significant and clinically relevant were not observed in favor of either treatment arm. CLINICAL TRIAL REGISTRATION: NCT02296125.
Authors: Nikolaus Magios; Farastuk Bozorgmehr; Anna-Lena Volckmar; Daniel Kazdal; Martina Kirchner; Felix J Herth; Claus-Peter Heussel; Florian Eichhorn; Michael Meister; Thomas Muley; Rami A Elshafie; Jürgen R Fischer; Martin Faehling; Mark Kriegsmann; Peter Schirmacher; Helge Bischoff; Albrecht Stenzinger; Michael Thomas; Petros Christopoulos Journal: Ther Adv Med Oncol Date: 2021-03-24 Impact factor: 8.168
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Authors: Annemarie C Eggen; Nadine M Richard; Ingeborg Bosma; Mathilde Jalving; Natasha B Leighl; Geoffrey Liu; Kenneth Mah; Randa Higazy; David B Shultz; Anna K L Reyners; Gary Rodin; Kim Edelstein Journal: Neurooncol Pract Date: 2021-09-07