Patient-Reported Outcomes with Durvalumab With or Without Tremelimumab Versus Standard Chemotherapy as First-Line Treatment of Metastatic Non–Small-Cell Lung Cancer (MYSTIC)

Edward B. Garon; Byoung Chul Cho; Niels Reinmuth; Ki Hyeong Lee; Alexander Luft; Myung Ju Ahn; Gilles Robinet; Sylvestre Le Moulec; Ronald Natale; Jeffrey Schneider; Frances A. Shepherd; Marina Chiara Garassino; Sarayut Lucien Geater; Zsolt Papai Szekely; Tran Van Ngoc; Feng Liu; Urban Scheuring; Nikunj Patel; Solange Peters; Naiyer A. Rizvi

doi:10.1016/j.cllc.2021.02.010

Patient-Reported Outcomes with Durvalumab With or Without Tremelimumab Versus Standard Chemotherapy as First-Line Treatment of Metastatic Non–Small-Cell Lung Cancer (MYSTIC)

Edward B. Garon, Byoung Chul Cho, Niels Reinmuth, Ki Hyeong Lee, Alexander Luft, Myung Ju Ahn, Gilles Robinet, Sylvestre Le Moulec, Ronald Natale, Jeffrey Schneider, Frances A. Shepherd, Marina Chiara Garassino, Sarayut Lucien Geater, Zsolt Papai Szekely, Tran Van Ngoc, Feng Liu, Urban Scheuring, Nikunj Patel, Solange Peters, Naiyer A. Rizvi

Department of Internal Medicine

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

7 Citations (Scopus)

Abstract

Background: The phase 3 MYSTIC study of durvalumab ± tremelimumab versus chemotherapy in metastatic non–small-cell lung cancer (NSCLC) patients with tumor cell (TC) programmed cell death ligand 1 (PD-L1) expression ≥ 25% did not meet its primary endpoints. We report patient-reported outcomes (PROs). Patients and Methods: Treatment-naïve patients were randomized (1:1:1) to durvalumab, durvalumab + tremelimumab, or chemotherapy. PROs were assessed in patients with PD-L1 TC ≥ 25% using EORTC Quality of Life Questionnaire (QLQ)-C30/LC13. Changes from baseline (12 months) for prespecified PRO endpoints of interest were analyzed by mixed model for repeated measures (MMRM) and time to deterioration (TTD) by stratified log-rank tests. Results: There were no between-arm differences in baseline PROs (N = 488). Between-arm differences in MMRM-adjusted mean changes from baseline favored at least one of the durvalumab-containing arms versus chemotherapy (nominal P < .01) for C30 fatigue: durvalumab (−9.5; 99% confidence interval [CI], −17.0 to −2.0), durvalumab + tremelimumab (−11.7; 99% CI, −19.4 to −4.1); and for C30 appetite loss: durvalumab (−11.9; 99% CI, −21.1 to −2.7). TTD was longer with at least one of the durvalumab-containing arms versus chemotherapy (nominal P < .01) for global health status/quality of life: durvalumab (hazard ratio [HR] = 0.7; 95% CI, 0.5-1.0), durvalumab + tremelimumab (HR = 0.7; 95% CI, 0.5-1.0); and for physical functioning: durvalumab (HR = 0.6; 95% CI, 0.4-0.8), durvalumab + tremelimumab (HR = 0.6; 95% CI, 0.5-0.9) (both C30); as well as for the key symptoms of dyspnea: durvalumab (HR = 0.6; 95% CI, 0.5-0.9), durvalumab + tremelimumab (HR = 0.7; 95% CI, 0.5-1.0) (both LC13); fatigue: durvalumab + tremelimumab (HR = 0.6; 95% CI, 0.4-0.8); and appetite loss: durvalumab (HR = 0.5; 95% CI, 0.4-0.7), durvalumab + tremelimumab (HR = 0.7; 95% CI, 0.5-0.9) (both C30). Conclusion: Durvalumab ± tremelimumab versus chemotherapy reduced symptom burden and improved TTD of PROs, suggesting it had no detrimental effects on quality of life in metastatic NSCLC patients.

Original language	English
Pages (from-to)	301-312.e8
Journal	Clinical Lung Cancer
Volume	22
Issue number	4
DOIs	https://doi.org/10.1016/j.cllc.2021.02.010
Publication status	Published - 2021 Jul

Bibliographical note

Funding Information:
The authors thank the patients, their families and caregivers, and all investigators involved in the MYSTIC study (NCT02453282). Medical writing support, which was in accordance with Good Publication Practice (GPP3) guidelines, was provided by Andrew Gannon, MS, MA, and Beena John, PhD, of Cirrus Communications (New York, NY), an Ashfield company, and was funded by AstraZeneca. The MYSTIC study (NCT02453282) was funded by AstraZeneca. E.B. Garon reports grants from AstraZeneca, Dynavax, Eli Lilly, Genentech, Iovance, Mirati, and Neon; grants and personal fees from BMS, EMD Serono, Merck, and Novartis; and personal fees from ABL, Boehringer Ingelheim, Dracen, Eisai, GSK, Sanofi, Shionogi, and Xilio, outside the submitted work. B.C. Cho reports grants from AbbVie, AstraZeneca, Bayer, Blueprint Medicines, Champions Oncology, Dizal Pharma, Dong-A ST, Eli Lilly, GI Innovation, Interpark Bio-Convergence Corp. Janssen, MedPacto, MOGAM Institute, MSD, Novartis, Ono, and Yuhan; personal fees from AstraZeneca, Blueprint Medicines, Boehringer Ingelheim, BMS, Champions Oncology, Eli Lilly, Gencurix Inc. Interpark Bio-Convergence Corp. Janssen, MedPacto, MSD, Novartis, Ono, Pfizer, Roche, Takeda, and Yuhan; and other from Bridgebio Therapeutics, Cyrus Therapeutics, DAAN Biotherapeutics, Gencurix Inc. Interpark Bio-Convergence Corp. KANAPH Therapeutic Inc. and TheraCanVac Inc. during the conduct of the study. N. Reinmuth reports personal fees from Amgen, AstraZeneca, BMS, Boehringer Ingelheim, MSD, Pfizer, Roche, and Takeda, outside the submitted work. K.H. Lee reports personal fees from BMS, MSD, Eli Lilly, Pfizer, and Yuhan, outside the submitted work. G. Robinet reports grants from AstraZeneca during the conduct of the study and grants from BMS and Boehringer Ingelheim and grants and non-financial support from MSD, outside the submitted work. R. Natale reports grants from Cedars-Sinai Medical Center during the conduct of the study; his spouse is a full-time employee of AstraZeneca. J. Schneider reports grants from Perlmutter Cancer Center at NYU Winthrop Langone Healthcare Network during the conduct of the study. F.A. Shepherd reports honoraria from AstraZeneca and stock ownership of AstraZeneca. M.C. Garassino reports grants and personal fees from AstraZeneca, Bayer, Blueprint Medicine, BMS, Celgene, Eli Lilly, GlaxoSmithKline, Incyte, Janssen, MSD, Novartis, Otsuka Pharma, Pfizer, Roche, Sanofi-Aventis, and Spectrum Pharmaceuticals; personal fees from Boehringer Ingelheim, Daiichi Sankyo, Inivata, Mirati Therapeutics, Seattle Genetics, Takeda, and Tiziana Sciences; grants from Bayer, Clovis, Exelisis, Ipsen, MedImmune, Merck KGaA, and Merck Serono; and non-financial support from Eli Lilly and MSD, outside the submitted work. S.L. Geater reports grants from Prince of Songkla University during the conduct of the study; grants and personal fees from AstraZeneca, Boehringer Ingelheim, and Roche; and grants from Novartis, outside the submitted work. F. Liu, U. Scheuring, and N. Patel are full-time employees of AstraZeneca with stock ownership. S. Peters reports personal fees from AbbVie, Amgen, AstraZeneca, Bayer, Biocartis, Bristol-Myers Squibb, Boehringer Ingelheim, Clovis, Daiichi Sankyo, Debiopharm, Eli Lilly, F. Hoffmann-La Roche, Foundation Medicine, Illumina, Janssen, Merck Sharp and Dohme, Merck Serono, Merrimack, Novartis, Pharma Mar, Pfizer, Regeneron, Sanofi, Seattle Genetics, and Takeda; non-financial support from Amgen, AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Clovis, F. Hoffmann-La Roche, Illumina, Merck Sharp and Dohme, Merck Serono, Novartis, Pfizer, and Sanofi; and personal fees from Bioinvent, outside the submitted work. N.A. Rizvi has received personal fees from AbbVie, Apricity, AstraZeneca, Boehringer Ingelheim, Calithera, Dracen, Editas, Eli Lilly, EMD Serono, G1 Therapeutics, Genentech, Gilead, GlaxoSmithKline, Illumina, Merck, Neogenomics, Novartis, and Takeda; personal fees and stock options from Arcus, Bellicum, Brooklyn ImmunoTherapeutics, and Gritstone; stock from Gritstone; and royalties related to a patent filed by Memorial Sloan Kettering Cancer Center for identifying determinants of cancer response to immunotherapy (PCT/US2015/062208), licensed to Personal Genome Diagnostics. The remaining authors have stated that they have no conflicts of interest.

Publisher Copyright:
© 2021 The Authors

All Science Journal Classification (ASJC) codes

Oncology
Pulmonary and Respiratory Medicine
Cancer Research

UN SDGs

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

Access to Document

10.1016/j.cllc.2021.02.010

Cite this

Garon, E. B., Cho, B. C., Reinmuth, N., Lee, K. H., Luft, A., Ahn, M. J., Robinet, G., Le Moulec, S., Natale, R., Schneider, J., Shepherd, F. A., Garassino, M. C., Geater, S. L., Szekely, Z. P., Van Ngoc, T., Liu, F., Scheuring, U., Patel, N., Peters, S., & Rizvi, N. A. (2021). Patient-Reported Outcomes with Durvalumab With or Without Tremelimumab Versus Standard Chemotherapy as First-Line Treatment of Metastatic Non–Small-Cell Lung Cancer (MYSTIC). Clinical Lung Cancer, 22(4), 301-312.e8. https://doi.org/10.1016/j.cllc.2021.02.010

@article{c5be93c4cd29450e8f2f62f4da67778a,

title = "Patient-Reported Outcomes with Durvalumab With or Without Tremelimumab Versus Standard Chemotherapy as First-Line Treatment of Metastatic Non–Small-Cell Lung Cancer (MYSTIC)",

abstract = "Background: The phase 3 MYSTIC study of durvalumab ± tremelimumab versus chemotherapy in metastatic non–small-cell lung cancer (NSCLC) patients with tumor cell (TC) programmed cell death ligand 1 (PD-L1) expression ≥ 25% did not meet its primary endpoints. We report patient-reported outcomes (PROs). Patients and Methods: Treatment-na{\"i}ve patients were randomized (1:1:1) to durvalumab, durvalumab + tremelimumab, or chemotherapy. PROs were assessed in patients with PD-L1 TC ≥ 25% using EORTC Quality of Life Questionnaire (QLQ)-C30/LC13. Changes from baseline (12 months) for prespecified PRO endpoints of interest were analyzed by mixed model for repeated measures (MMRM) and time to deterioration (TTD) by stratified log-rank tests. Results: There were no between-arm differences in baseline PROs (N = 488). Between-arm differences in MMRM-adjusted mean changes from baseline favored at least one of the durvalumab-containing arms versus chemotherapy (nominal P < .01) for C30 fatigue: durvalumab (−9.5; 99% confidence interval [CI], −17.0 to −2.0), durvalumab + tremelimumab (−11.7; 99% CI, −19.4 to −4.1); and for C30 appetite loss: durvalumab (−11.9; 99% CI, −21.1 to −2.7). TTD was longer with at least one of the durvalumab-containing arms versus chemotherapy (nominal P < .01) for global health status/quality of life: durvalumab (hazard ratio [HR] = 0.7; 95% CI, 0.5-1.0), durvalumab + tremelimumab (HR = 0.7; 95% CI, 0.5-1.0); and for physical functioning: durvalumab (HR = 0.6; 95% CI, 0.4-0.8), durvalumab + tremelimumab (HR = 0.6; 95% CI, 0.5-0.9) (both C30); as well as for the key symptoms of dyspnea: durvalumab (HR = 0.6; 95% CI, 0.5-0.9), durvalumab + tremelimumab (HR = 0.7; 95% CI, 0.5-1.0) (both LC13); fatigue: durvalumab + tremelimumab (HR = 0.6; 95% CI, 0.4-0.8); and appetite loss: durvalumab (HR = 0.5; 95% CI, 0.4-0.7), durvalumab + tremelimumab (HR = 0.7; 95% CI, 0.5-0.9) (both C30). Conclusion: Durvalumab ± tremelimumab versus chemotherapy reduced symptom burden and improved TTD of PROs, suggesting it had no detrimental effects on quality of life in metastatic NSCLC patients.",

author = "Garon, {Edward B.} and Cho, {Byoung Chul} and Niels Reinmuth and Lee, {Ki Hyeong} and Alexander Luft and Ahn, {Myung Ju} and Gilles Robinet and {Le Moulec}, Sylvestre and Ronald Natale and Jeffrey Schneider and Shepherd, {Frances A.} and Garassino, {Marina Chiara} and Geater, {Sarayut Lucien} and Szekely, {Zsolt Papai} and {Van Ngoc}, Tran and Feng Liu and Urban Scheuring and Nikunj Patel and Solange Peters and Rizvi, {Naiyer A.}",

note = "Funding Information: The authors thank the patients, their families and caregivers, and all investigators involved in the MYSTIC study (NCT02453282). Medical writing support, which was in accordance with Good Publication Practice (GPP3) guidelines, was provided by Andrew Gannon, MS, MA, and Beena John, PhD, of Cirrus Communications (New York, NY), an Ashfield company, and was funded by AstraZeneca. The MYSTIC study (NCT02453282) was funded by AstraZeneca. E.B. Garon reports grants from AstraZeneca, Dynavax, Eli Lilly, Genentech, Iovance, Mirati, and Neon; grants and personal fees from BMS, EMD Serono, Merck, and Novartis; and personal fees from ABL, Boehringer Ingelheim, Dracen, Eisai, GSK, Sanofi, Shionogi, and Xilio, outside the submitted work. B.C. Cho reports grants from AbbVie, AstraZeneca, Bayer, Blueprint Medicines, Champions Oncology, Dizal Pharma, Dong-A ST, Eli Lilly, GI Innovation, Interpark Bio-Convergence Corp. Janssen, MedPacto, MOGAM Institute, MSD, Novartis, Ono, and Yuhan; personal fees from AstraZeneca, Blueprint Medicines, Boehringer Ingelheim, BMS, Champions Oncology, Eli Lilly, Gencurix Inc. Interpark Bio-Convergence Corp. Janssen, MedPacto, MSD, Novartis, Ono, Pfizer, Roche, Takeda, and Yuhan; and other from Bridgebio Therapeutics, Cyrus Therapeutics, DAAN Biotherapeutics, Gencurix Inc. Interpark Bio-Convergence Corp. KANAPH Therapeutic Inc. and TheraCanVac Inc. during the conduct of the study. N. Reinmuth reports personal fees from Amgen, AstraZeneca, BMS, Boehringer Ingelheim, MSD, Pfizer, Roche, and Takeda, outside the submitted work. K.H. Lee reports personal fees from BMS, MSD, Eli Lilly, Pfizer, and Yuhan, outside the submitted work. G. Robinet reports grants from AstraZeneca during the conduct of the study and grants from BMS and Boehringer Ingelheim and grants and non-financial support from MSD, outside the submitted work. R. Natale reports grants from Cedars-Sinai Medical Center during the conduct of the study; his spouse is a full-time employee of AstraZeneca. J. Schneider reports grants from Perlmutter Cancer Center at NYU Winthrop Langone Healthcare Network during the conduct of the study. F.A. Shepherd reports honoraria from AstraZeneca and stock ownership of AstraZeneca. M.C. Garassino reports grants and personal fees from AstraZeneca, Bayer, Blueprint Medicine, BMS, Celgene, Eli Lilly, GlaxoSmithKline, Incyte, Janssen, MSD, Novartis, Otsuka Pharma, Pfizer, Roche, Sanofi-Aventis, and Spectrum Pharmaceuticals; personal fees from Boehringer Ingelheim, Daiichi Sankyo, Inivata, Mirati Therapeutics, Seattle Genetics, Takeda, and Tiziana Sciences; grants from Bayer, Clovis, Exelisis, Ipsen, MedImmune, Merck KGaA, and Merck Serono; and non-financial support from Eli Lilly and MSD, outside the submitted work. S.L. Geater reports grants from Prince of Songkla University during the conduct of the study; grants and personal fees from AstraZeneca, Boehringer Ingelheim, and Roche; and grants from Novartis, outside the submitted work. F. Liu, U. Scheuring, and N. Patel are full-time employees of AstraZeneca with stock ownership. S. Peters reports personal fees from AbbVie, Amgen, AstraZeneca, Bayer, Biocartis, Bristol-Myers Squibb, Boehringer Ingelheim, Clovis, Daiichi Sankyo, Debiopharm, Eli Lilly, F. Hoffmann-La Roche, Foundation Medicine, Illumina, Janssen, Merck Sharp and Dohme, Merck Serono, Merrimack, Novartis, Pharma Mar, Pfizer, Regeneron, Sanofi, Seattle Genetics, and Takeda; non-financial support from Amgen, AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Clovis, F. Hoffmann-La Roche, Illumina, Merck Sharp and Dohme, Merck Serono, Novartis, Pfizer, and Sanofi; and personal fees from Bioinvent, outside the submitted work. N.A. Rizvi has received personal fees from AbbVie, Apricity, AstraZeneca, Boehringer Ingelheim, Calithera, Dracen, Editas, Eli Lilly, EMD Serono, G1 Therapeutics, Genentech, Gilead, GlaxoSmithKline, Illumina, Merck, Neogenomics, Novartis, and Takeda; personal fees and stock options from Arcus, Bellicum, Brooklyn ImmunoTherapeutics, and Gritstone; stock from Gritstone; and royalties related to a patent filed by Memorial Sloan Kettering Cancer Center for identifying determinants of cancer response to immunotherapy (PCT/US2015/062208), licensed to Personal Genome Diagnostics. The remaining authors have stated that they have no conflicts of interest. Publisher Copyright: {\textcopyright} 2021 The Authors",

year = "2021",

month = jul,

doi = "10.1016/j.cllc.2021.02.010",

language = "English",

volume = "22",

pages = "301--312.e8",

journal = "Clinical Lung Cancer",

issn = "1525-7304",

publisher = "Elsevier",

number = "4",

}

Garon, EB, Cho, BC, Reinmuth, N, Lee, KH, Luft, A, Ahn, MJ, Robinet, G, Le Moulec, S, Natale, R, Schneider, J, Shepherd, FA, Garassino, MC, Geater, SL, Szekely, ZP, Van Ngoc, T, Liu, F, Scheuring, U, Patel, N, Peters, S & Rizvi, NA 2021, 'Patient-Reported Outcomes with Durvalumab With or Without Tremelimumab Versus Standard Chemotherapy as First-Line Treatment of Metastatic Non–Small-Cell Lung Cancer (MYSTIC)', Clinical Lung Cancer, vol. 22, no. 4, pp. 301-312.e8. https://doi.org/10.1016/j.cllc.2021.02.010

Patient-Reported Outcomes with Durvalumab With or Without Tremelimumab Versus Standard Chemotherapy as First-Line Treatment of Metastatic Non–Small-Cell Lung Cancer (MYSTIC). / Garon, Edward B.; Cho, Byoung Chul; Reinmuth, Niels et al.
In: Clinical Lung Cancer, Vol. 22, No. 4, 07.2021, p. 301-312.e8.

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

TY - JOUR

T1 - Patient-Reported Outcomes with Durvalumab With or Without Tremelimumab Versus Standard Chemotherapy as First-Line Treatment of Metastatic Non–Small-Cell Lung Cancer (MYSTIC)

AU - Garon, Edward B.

AU - Cho, Byoung Chul

AU - Reinmuth, Niels

AU - Lee, Ki Hyeong

AU - Luft, Alexander

AU - Ahn, Myung Ju

AU - Robinet, Gilles

AU - Le Moulec, Sylvestre

AU - Natale, Ronald

AU - Schneider, Jeffrey

AU - Shepherd, Frances A.

AU - Garassino, Marina Chiara

AU - Geater, Sarayut Lucien

AU - Szekely, Zsolt Papai

AU - Van Ngoc, Tran

AU - Liu, Feng

AU - Scheuring, Urban

AU - Patel, Nikunj

AU - Peters, Solange

AU - Rizvi, Naiyer A.

N1 - Funding Information: The authors thank the patients, their families and caregivers, and all investigators involved in the MYSTIC study (NCT02453282). Medical writing support, which was in accordance with Good Publication Practice (GPP3) guidelines, was provided by Andrew Gannon, MS, MA, and Beena John, PhD, of Cirrus Communications (New York, NY), an Ashfield company, and was funded by AstraZeneca. The MYSTIC study (NCT02453282) was funded by AstraZeneca. E.B. Garon reports grants from AstraZeneca, Dynavax, Eli Lilly, Genentech, Iovance, Mirati, and Neon; grants and personal fees from BMS, EMD Serono, Merck, and Novartis; and personal fees from ABL, Boehringer Ingelheim, Dracen, Eisai, GSK, Sanofi, Shionogi, and Xilio, outside the submitted work. B.C. Cho reports grants from AbbVie, AstraZeneca, Bayer, Blueprint Medicines, Champions Oncology, Dizal Pharma, Dong-A ST, Eli Lilly, GI Innovation, Interpark Bio-Convergence Corp. Janssen, MedPacto, MOGAM Institute, MSD, Novartis, Ono, and Yuhan; personal fees from AstraZeneca, Blueprint Medicines, Boehringer Ingelheim, BMS, Champions Oncology, Eli Lilly, Gencurix Inc. Interpark Bio-Convergence Corp. Janssen, MedPacto, MSD, Novartis, Ono, Pfizer, Roche, Takeda, and Yuhan; and other from Bridgebio Therapeutics, Cyrus Therapeutics, DAAN Biotherapeutics, Gencurix Inc. Interpark Bio-Convergence Corp. KANAPH Therapeutic Inc. and TheraCanVac Inc. during the conduct of the study. N. Reinmuth reports personal fees from Amgen, AstraZeneca, BMS, Boehringer Ingelheim, MSD, Pfizer, Roche, and Takeda, outside the submitted work. K.H. Lee reports personal fees from BMS, MSD, Eli Lilly, Pfizer, and Yuhan, outside the submitted work. G. Robinet reports grants from AstraZeneca during the conduct of the study and grants from BMS and Boehringer Ingelheim and grants and non-financial support from MSD, outside the submitted work. R. Natale reports grants from Cedars-Sinai Medical Center during the conduct of the study; his spouse is a full-time employee of AstraZeneca. J. Schneider reports grants from Perlmutter Cancer Center at NYU Winthrop Langone Healthcare Network during the conduct of the study. F.A. Shepherd reports honoraria from AstraZeneca and stock ownership of AstraZeneca. M.C. Garassino reports grants and personal fees from AstraZeneca, Bayer, Blueprint Medicine, BMS, Celgene, Eli Lilly, GlaxoSmithKline, Incyte, Janssen, MSD, Novartis, Otsuka Pharma, Pfizer, Roche, Sanofi-Aventis, and Spectrum Pharmaceuticals; personal fees from Boehringer Ingelheim, Daiichi Sankyo, Inivata, Mirati Therapeutics, Seattle Genetics, Takeda, and Tiziana Sciences; grants from Bayer, Clovis, Exelisis, Ipsen, MedImmune, Merck KGaA, and Merck Serono; and non-financial support from Eli Lilly and MSD, outside the submitted work. S.L. Geater reports grants from Prince of Songkla University during the conduct of the study; grants and personal fees from AstraZeneca, Boehringer Ingelheim, and Roche; and grants from Novartis, outside the submitted work. F. Liu, U. Scheuring, and N. Patel are full-time employees of AstraZeneca with stock ownership. S. Peters reports personal fees from AbbVie, Amgen, AstraZeneca, Bayer, Biocartis, Bristol-Myers Squibb, Boehringer Ingelheim, Clovis, Daiichi Sankyo, Debiopharm, Eli Lilly, F. Hoffmann-La Roche, Foundation Medicine, Illumina, Janssen, Merck Sharp and Dohme, Merck Serono, Merrimack, Novartis, Pharma Mar, Pfizer, Regeneron, Sanofi, Seattle Genetics, and Takeda; non-financial support from Amgen, AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Clovis, F. Hoffmann-La Roche, Illumina, Merck Sharp and Dohme, Merck Serono, Novartis, Pfizer, and Sanofi; and personal fees from Bioinvent, outside the submitted work. N.A. Rizvi has received personal fees from AbbVie, Apricity, AstraZeneca, Boehringer Ingelheim, Calithera, Dracen, Editas, Eli Lilly, EMD Serono, G1 Therapeutics, Genentech, Gilead, GlaxoSmithKline, Illumina, Merck, Neogenomics, Novartis, and Takeda; personal fees and stock options from Arcus, Bellicum, Brooklyn ImmunoTherapeutics, and Gritstone; stock from Gritstone; and royalties related to a patent filed by Memorial Sloan Kettering Cancer Center for identifying determinants of cancer response to immunotherapy (PCT/US2015/062208), licensed to Personal Genome Diagnostics. The remaining authors have stated that they have no conflicts of interest. Publisher Copyright: © 2021 The Authors

PY - 2021/7

Y1 - 2021/7

N2 - Background: The phase 3 MYSTIC study of durvalumab ± tremelimumab versus chemotherapy in metastatic non–small-cell lung cancer (NSCLC) patients with tumor cell (TC) programmed cell death ligand 1 (PD-L1) expression ≥ 25% did not meet its primary endpoints. We report patient-reported outcomes (PROs). Patients and Methods: Treatment-naïve patients were randomized (1:1:1) to durvalumab, durvalumab + tremelimumab, or chemotherapy. PROs were assessed in patients with PD-L1 TC ≥ 25% using EORTC Quality of Life Questionnaire (QLQ)-C30/LC13. Changes from baseline (12 months) for prespecified PRO endpoints of interest were analyzed by mixed model for repeated measures (MMRM) and time to deterioration (TTD) by stratified log-rank tests. Results: There were no between-arm differences in baseline PROs (N = 488). Between-arm differences in MMRM-adjusted mean changes from baseline favored at least one of the durvalumab-containing arms versus chemotherapy (nominal P < .01) for C30 fatigue: durvalumab (−9.5; 99% confidence interval [CI], −17.0 to −2.0), durvalumab + tremelimumab (−11.7; 99% CI, −19.4 to −4.1); and for C30 appetite loss: durvalumab (−11.9; 99% CI, −21.1 to −2.7). TTD was longer with at least one of the durvalumab-containing arms versus chemotherapy (nominal P < .01) for global health status/quality of life: durvalumab (hazard ratio [HR] = 0.7; 95% CI, 0.5-1.0), durvalumab + tremelimumab (HR = 0.7; 95% CI, 0.5-1.0); and for physical functioning: durvalumab (HR = 0.6; 95% CI, 0.4-0.8), durvalumab + tremelimumab (HR = 0.6; 95% CI, 0.5-0.9) (both C30); as well as for the key symptoms of dyspnea: durvalumab (HR = 0.6; 95% CI, 0.5-0.9), durvalumab + tremelimumab (HR = 0.7; 95% CI, 0.5-1.0) (both LC13); fatigue: durvalumab + tremelimumab (HR = 0.6; 95% CI, 0.4-0.8); and appetite loss: durvalumab (HR = 0.5; 95% CI, 0.4-0.7), durvalumab + tremelimumab (HR = 0.7; 95% CI, 0.5-0.9) (both C30). Conclusion: Durvalumab ± tremelimumab versus chemotherapy reduced symptom burden and improved TTD of PROs, suggesting it had no detrimental effects on quality of life in metastatic NSCLC patients.

AB - Background: The phase 3 MYSTIC study of durvalumab ± tremelimumab versus chemotherapy in metastatic non–small-cell lung cancer (NSCLC) patients with tumor cell (TC) programmed cell death ligand 1 (PD-L1) expression ≥ 25% did not meet its primary endpoints. We report patient-reported outcomes (PROs). Patients and Methods: Treatment-naïve patients were randomized (1:1:1) to durvalumab, durvalumab + tremelimumab, or chemotherapy. PROs were assessed in patients with PD-L1 TC ≥ 25% using EORTC Quality of Life Questionnaire (QLQ)-C30/LC13. Changes from baseline (12 months) for prespecified PRO endpoints of interest were analyzed by mixed model for repeated measures (MMRM) and time to deterioration (TTD) by stratified log-rank tests. Results: There were no between-arm differences in baseline PROs (N = 488). Between-arm differences in MMRM-adjusted mean changes from baseline favored at least one of the durvalumab-containing arms versus chemotherapy (nominal P < .01) for C30 fatigue: durvalumab (−9.5; 99% confidence interval [CI], −17.0 to −2.0), durvalumab + tremelimumab (−11.7; 99% CI, −19.4 to −4.1); and for C30 appetite loss: durvalumab (−11.9; 99% CI, −21.1 to −2.7). TTD was longer with at least one of the durvalumab-containing arms versus chemotherapy (nominal P < .01) for global health status/quality of life: durvalumab (hazard ratio [HR] = 0.7; 95% CI, 0.5-1.0), durvalumab + tremelimumab (HR = 0.7; 95% CI, 0.5-1.0); and for physical functioning: durvalumab (HR = 0.6; 95% CI, 0.4-0.8), durvalumab + tremelimumab (HR = 0.6; 95% CI, 0.5-0.9) (both C30); as well as for the key symptoms of dyspnea: durvalumab (HR = 0.6; 95% CI, 0.5-0.9), durvalumab + tremelimumab (HR = 0.7; 95% CI, 0.5-1.0) (both LC13); fatigue: durvalumab + tremelimumab (HR = 0.6; 95% CI, 0.4-0.8); and appetite loss: durvalumab (HR = 0.5; 95% CI, 0.4-0.7), durvalumab + tremelimumab (HR = 0.7; 95% CI, 0.5-0.9) (both C30). Conclusion: Durvalumab ± tremelimumab versus chemotherapy reduced symptom burden and improved TTD of PROs, suggesting it had no detrimental effects on quality of life in metastatic NSCLC patients.

UR - http://www.scopus.com/inward/record.url?scp=85103263830&partnerID=8YFLogxK

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U2 - 10.1016/j.cllc.2021.02.010

DO - 10.1016/j.cllc.2021.02.010

M3 - Article

C2 - 33775558

AN - SCOPUS:85103263830

SN - 1525-7304

VL - 22

SP - 301-312.e8

JO - Clinical Lung Cancer

JF - Clinical Lung Cancer

IS - 4

ER -

Patient-Reported Outcomes with Durvalumab With or Without Tremelimumab Versus Standard Chemotherapy as First-Line Treatment of Metastatic Non–Small-Cell Lung Cancer (MYSTIC)

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