Patient-reported outcomes from FLAURA: Osimertinib versus erlotinib or gefitinib in patients with EGFR-mutated advanced non-small-cell lung cancer

Natasha B. Leighl; Nina Karaseva; Kazuhiko Nakagawa; Byoung Chul Cho; Jhanelle E. Gray; Tina Hovey; Andrew Walding; Anna Rydén; Silvia Novello

doi:10.1016/j.ejca.2019.11.006

Patient-reported outcomes from FLAURA: Osimertinib versus erlotinib or gefitinib in patients with EGFR-mutated advanced non-small-cell lung cancer

Natasha B. Leighl, Nina Karaseva, Kazuhiko Nakagawa, Byoung Chul Cho, Jhanelle E. Gray, Tina Hovey, Andrew Walding, Anna Rydén, Silvia Novello

Department of Internal Medicine

Research output: Contribution to journal › Article › peer-review

31 Citations (Scopus)

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.

Original language	English
Pages (from-to)	49-57
Number of pages	9
Journal	European Journal of Cancer
Volume	125
DOIs	https://doi.org/10.1016/j.ejca.2019.11.006
Publication status	Published - 2020 Jan

Bibliographical note

Funding Information:
The study (NCT02296125) was funded by AstraZeneca, Cambridge, UK, the manufacturer of osimertinib.N.B.L. has received fees for independent continuing medical education from AstraZeneca, Bristol-Myers Squibb and Merck Sharp & Dohme and research funding from Array. N.K. has no disclosures to report. K.N. has received research funding from A2 Healthcare, AbbVie, Astellas Pharma, Bristol-Myers Squibb, Chugai Pharmaceutical, Daiichi Sankyo, Eisai, Eli Lilly, EP-CRSU, Gritstone Oncology, ICON Japan, inVentiv Health, Linical, Merck Sharp & Dohme, Novartis, Ono Pharmaceutical, Parexel International, Quintiles, Taiho Pharmaceutical, and Takeda Pharmaceutical and fees from Astellas Pharma, AstraZeneca, Bristol-Myers Squibb, Eli Lilly, Merck Sharp & Dohme, Nichi-Iko Pharmaceutical, Nippon Boehringer Ingelheim, Novartis, Ono Pharmaceutical, Pfizer, SymBio Pharmaceuticals, and Taiho Pharmaceutical. He has also acted as a consultant for Astellas Pharma and Ono Pharmaceutical. B.C.C. has no disclosures to report. J.E.G. is an advisor for and receives research funding from AstraZeneca. T.H. is a consultant statistician (PHASTAR) for AstraZeneca. A.W. and A.R. are employees of AstraZeneca and hold AstraZeneca shares. S.N. is a speaker for AstraZeneca, Bristol-Myers Squibb, Eli Lilly, Merck Sharp & Dohme, Roche, and Takeda Pharmaceutical.We thank the patients and families that participated in the FLAURA trial. Medical writing support was provided by Anja Becher PhD of Oxford PharmaGenesis, Oxford, UK, funded by AstraZeneca. Data underlying the findings described in this manuscript may be obtained in accordance with AstraZeneca's data sharing policy described at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

Funding Information:
N.B.L. has received fees for independent continuing medical education from AstraZeneca , Bristol-Myers Squibb and Merck Sharp & Dohme and research funding from Array . N.K. has no disclosures to report. K.N. has received research funding from A2 Healthcare , AbbVie , Astellas Pharma , Bristol-Myers Squibb , Chugai Pharmaceutical , Daiichi Sankyo , Eisai , Eli Lilly , EP-CRSU , Gritstone Oncology , ICON Japan, inVentiv Health , Linical , Merck Sharp & Dohme , Novartis , Ono Pharmaceutical , Parexel International , Quintiles , Taiho Pharmaceutical , and Takeda Pharmaceutical and fees from Astellas Pharma , AstraZeneca , Bristol-Myers Squibb , Eli Lilly , Merck Sharp & Dohme , Nichi-Iko Pharmaceutical , Nippon Boehringer Ingelheim , Novartis , Ono Pharmaceutical , Pfizer , SymBio Pharmaceuticals , and Taiho Pharmaceutical . He has also acted as a consultant for Astellas Pharma and Ono Pharmaceutical . B.C.C. has no disclosures to report. J.E.G. is an advisor for and receives research funding from AstraZeneca . T.H. is a consultant statistician (PHASTAR) for AstraZeneca . A.W. and A.R. are employees of AstraZeneca and hold AstraZeneca shares. S.N. is a speaker for AstraZeneca , Bristol-Myers Squibb , Eli Lilly , Merck Sharp & Dohme , Roche , and Takeda Pharmaceutical.

Publisher Copyright:
© 2019 The Authors

All Science Journal Classification (ASJC) codes

Oncology
Cancer Research

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.ejca.2019.11.006

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@article{29f1decef1d04673bf525e94702c9ad1,

title = "Patient-reported outcomes from FLAURA: Osimertinib versus erlotinib or gefitinib in patients with EGFR-mutated advanced non-small-cell lung cancer",

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.",

author = "Leighl, {Natasha B.} and Nina Karaseva and Kazuhiko Nakagawa and Cho, {Byoung Chul} and Gray, {Jhanelle E.} and Tina Hovey and Andrew Walding and Anna Ryd{\'e}n and Silvia Novello",

note = "Funding Information: The study (NCT02296125) was funded by AstraZeneca, Cambridge, UK, the manufacturer of osimertinib.N.B.L. has received fees for independent continuing medical education from AstraZeneca, Bristol-Myers Squibb and Merck Sharp & Dohme and research funding from Array. N.K. has no disclosures to report. K.N. has received research funding from A2 Healthcare, AbbVie, Astellas Pharma, Bristol-Myers Squibb, Chugai Pharmaceutical, Daiichi Sankyo, Eisai, Eli Lilly, EP-CRSU, Gritstone Oncology, ICON Japan, inVentiv Health, Linical, Merck Sharp & Dohme, Novartis, Ono Pharmaceutical, Parexel International, Quintiles, Taiho Pharmaceutical, and Takeda Pharmaceutical and fees from Astellas Pharma, AstraZeneca, Bristol-Myers Squibb, Eli Lilly, Merck Sharp & Dohme, Nichi-Iko Pharmaceutical, Nippon Boehringer Ingelheim, Novartis, Ono Pharmaceutical, Pfizer, SymBio Pharmaceuticals, and Taiho Pharmaceutical. He has also acted as a consultant for Astellas Pharma and Ono Pharmaceutical. B.C.C. has no disclosures to report. J.E.G. is an advisor for and receives research funding from AstraZeneca. T.H. is a consultant statistician (PHASTAR) for AstraZeneca. A.W. and A.R. are employees of AstraZeneca and hold AstraZeneca shares. S.N. is a speaker for AstraZeneca, Bristol-Myers Squibb, Eli Lilly, Merck Sharp & Dohme, Roche, and Takeda Pharmaceutical.We thank the patients and families that participated in the FLAURA trial. Medical writing support was provided by Anja Becher PhD of Oxford PharmaGenesis, Oxford, UK, funded by AstraZeneca. Data underlying the findings described in this manuscript may be obtained in accordance with AstraZeneca's data sharing policy described at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. Funding Information: N.B.L. has received fees for independent continuing medical education from AstraZeneca , Bristol-Myers Squibb and Merck Sharp & Dohme and research funding from Array . N.K. has no disclosures to report. K.N. has received research funding from A2 Healthcare , AbbVie , Astellas Pharma , Bristol-Myers Squibb , Chugai Pharmaceutical , Daiichi Sankyo , Eisai , Eli Lilly , EP-CRSU , Gritstone Oncology , ICON Japan, inVentiv Health , Linical , Merck Sharp & Dohme , Novartis , Ono Pharmaceutical , Parexel International , Quintiles , Taiho Pharmaceutical , and Takeda Pharmaceutical and fees from Astellas Pharma , AstraZeneca , Bristol-Myers Squibb , Eli Lilly , Merck Sharp & Dohme , Nichi-Iko Pharmaceutical , Nippon Boehringer Ingelheim , Novartis , Ono Pharmaceutical , Pfizer , SymBio Pharmaceuticals , and Taiho Pharmaceutical . He has also acted as a consultant for Astellas Pharma and Ono Pharmaceutical . B.C.C. has no disclosures to report. J.E.G. is an advisor for and receives research funding from AstraZeneca . T.H. is a consultant statistician (PHASTAR) for AstraZeneca . A.W. and A.R. are employees of AstraZeneca and hold AstraZeneca shares. S.N. is a speaker for AstraZeneca , Bristol-Myers Squibb , Eli Lilly , Merck Sharp & Dohme , Roche , and Takeda Pharmaceutical. Publisher Copyright: {\textcopyright} 2019 The Authors",

year = "2020",

month = jan,

doi = "10.1016/j.ejca.2019.11.006",

language = "English",

volume = "125",

pages = "49--57",

journal = "European Journal of Cancer",

issn = "0959-8049",

publisher = "Elsevier Limited",

}

TY - JOUR

T1 - Patient-reported outcomes from FLAURA

T2 - Osimertinib versus erlotinib or gefitinib in patients with EGFR-mutated advanced non-small-cell lung cancer

AU - Leighl, Natasha B.

AU - Karaseva, Nina

AU - Nakagawa, Kazuhiko

AU - Cho, Byoung Chul

AU - Gray, Jhanelle E.

AU - Hovey, Tina

AU - Walding, Andrew

AU - Rydén, Anna

AU - Novello, Silvia

N1 - Funding Information: The study (NCT02296125) was funded by AstraZeneca, Cambridge, UK, the manufacturer of osimertinib.N.B.L. has received fees for independent continuing medical education from AstraZeneca, Bristol-Myers Squibb and Merck Sharp & Dohme and research funding from Array. N.K. has no disclosures to report. K.N. has received research funding from A2 Healthcare, AbbVie, Astellas Pharma, Bristol-Myers Squibb, Chugai Pharmaceutical, Daiichi Sankyo, Eisai, Eli Lilly, EP-CRSU, Gritstone Oncology, ICON Japan, inVentiv Health, Linical, Merck Sharp & Dohme, Novartis, Ono Pharmaceutical, Parexel International, Quintiles, Taiho Pharmaceutical, and Takeda Pharmaceutical and fees from Astellas Pharma, AstraZeneca, Bristol-Myers Squibb, Eli Lilly, Merck Sharp & Dohme, Nichi-Iko Pharmaceutical, Nippon Boehringer Ingelheim, Novartis, Ono Pharmaceutical, Pfizer, SymBio Pharmaceuticals, and Taiho Pharmaceutical. He has also acted as a consultant for Astellas Pharma and Ono Pharmaceutical. B.C.C. has no disclosures to report. J.E.G. is an advisor for and receives research funding from AstraZeneca. T.H. is a consultant statistician (PHASTAR) for AstraZeneca. A.W. and A.R. are employees of AstraZeneca and hold AstraZeneca shares. S.N. is a speaker for AstraZeneca, Bristol-Myers Squibb, Eli Lilly, Merck Sharp & Dohme, Roche, and Takeda Pharmaceutical.We thank the patients and families that participated in the FLAURA trial. Medical writing support was provided by Anja Becher PhD of Oxford PharmaGenesis, Oxford, UK, funded by AstraZeneca. Data underlying the findings described in this manuscript may be obtained in accordance with AstraZeneca's data sharing policy described at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. Funding Information: N.B.L. has received fees for independent continuing medical education from AstraZeneca , Bristol-Myers Squibb and Merck Sharp & Dohme and research funding from Array . N.K. has no disclosures to report. K.N. has received research funding from A2 Healthcare , AbbVie , Astellas Pharma , Bristol-Myers Squibb , Chugai Pharmaceutical , Daiichi Sankyo , Eisai , Eli Lilly , EP-CRSU , Gritstone Oncology , ICON Japan, inVentiv Health , Linical , Merck Sharp & Dohme , Novartis , Ono Pharmaceutical , Parexel International , Quintiles , Taiho Pharmaceutical , and Takeda Pharmaceutical and fees from Astellas Pharma , AstraZeneca , Bristol-Myers Squibb , Eli Lilly , Merck Sharp & Dohme , Nichi-Iko Pharmaceutical , Nippon Boehringer Ingelheim , Novartis , Ono Pharmaceutical , Pfizer , SymBio Pharmaceuticals , and Taiho Pharmaceutical . He has also acted as a consultant for Astellas Pharma and Ono Pharmaceutical . B.C.C. has no disclosures to report. J.E.G. is an advisor for and receives research funding from AstraZeneca . T.H. is a consultant statistician (PHASTAR) for AstraZeneca . A.W. and A.R. are employees of AstraZeneca and hold AstraZeneca shares. S.N. is a speaker for AstraZeneca , Bristol-Myers Squibb , Eli Lilly , Merck Sharp & Dohme , Roche , and Takeda Pharmaceutical. Publisher Copyright: © 2019 The Authors

PY - 2020/1

Y1 - 2020/1

N2 - 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.

AB - 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.

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U2 - 10.1016/j.ejca.2019.11.006

DO - 10.1016/j.ejca.2019.11.006

M3 - Article

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AN - SCOPUS:85076114162

SN - 0959-8049

VL - 125

SP - 49

EP - 57

JO - European Journal of Cancer

JF - European Journal of Cancer

ER -

Patient-reported outcomes from FLAURA: Osimertinib versus erlotinib or gefitinib in patients with EGFR-mutated advanced non-small-cell lung cancer

Abstract

Bibliographical note

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UN SDGs

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