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


Journal

Clinical lung cancer
ISSN: 1938-0690
Titre abrégé: Clin Lung Cancer
Pays: United States
ID NLM: 100893225

Informations de publication

Date de publication:
07 2021
Historique:
received: 21 12 2020
accepted: 15 02 2021
pubmed: 30 3 2021
medline: 7 1 2022
entrez: 29 3 2021
Statut: ppublish

Résumé

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). 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. 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). 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.

Sections du résumé

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.

Identifiants

pubmed: 33775558
pii: S1525-7304(21)00033-4
doi: 10.1016/j.cllc.2021.02.010
pii:
doi:

Substances chimiques

Antibodies, Monoclonal 0
Antibodies, Monoclonal, Humanized 0
B7-H1 Antigen 0
CD274 protein, human 0
durvalumab 28X28X9OKV
tremelimumab QEN1X95CIX

Banques de données

ClinicalTrials.gov
['NCT02453282', 'NCT02453282']

Types de publication

Clinical Trial, Phase III Comparative Study Journal Article Multicenter Study Randomized Controlled Trial Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

301-312.e8

Informations de copyright

Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.

Auteurs

Edward B Garon (EB)

David Geffen School of Medicine, University of California/TRIO-US Network, Los Angeles, CA. Electronic address: egaron@mednet.ucla.edu.

Byoung Chul Cho (BC)

Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, South Korea.

Niels Reinmuth (N)

Asklepios Lung Clinic, Munich-Gauting, Germany.

Ki Hyeong Lee (KH)

Chungbuk National University Hospital, Chungbuk National University College of Medicine, Cheongju, South Korea.

Alexander Luft (A)

Department of Oncology No. 1 (Thoracic Surgery), Leningrad Regional Clinical Hospital, St. Petersburg, Russia.

Myung-Ju Ahn (MJ)

Department of Hematology and Oncology, Samsung Medical Center, Sungkyunkwan University, Seoul, South Korea.

Gilles Robinet (G)

Institut de Cancerologie, Centre Hospitalier Régional Universitaire de Brest-Hôpital Morvan, Brest, France.

Sylvestre Le Moulec (S)

Department of Medical Oncology, Institut Bergonnié, Bordeaux Cedex, France.

Ronald Natale (R)

Cedars-Sinai Comprehensive Cancer Center, Los Angeles, CA.

Jeffrey Schneider (J)

Department of Hematology and Oncology, NYU Winthrop Hospital, Mineola, NY.

Frances A Shepherd (FA)

Princess Margaret Cancer Centre and the Department of Medicine, University of Toronto, Toronto, Ontario, Canada.

Marina Chiara Garassino (MC)

Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.

Sarayut Lucien Geater (SL)

Department of Internal Medicine, Prince of Songkla University, Songkhla, Thailand.

Zsolt Papai Szekely (ZP)

St. George Hospital of Fejer County, Szekesfehervar, Hungary.

Tran Van Ngoc (T)

Cho Ray Hospital, Ho Chi Minh City, Vietnam.

Feng Liu (F)

AstraZeneca, Gaithersburg, MD.

Urban Scheuring (U)

AstraZeneca, Cambridge, United Kingdom.

Nikunj Patel (N)

AstraZeneca, Gaithersburg, MD.

Solange Peters (S)

Department of Oncology, Centre Hospitalier Universitaire Vaudois, Lausanne University, Lausanne, Switzerland.

Naiyer A Rizvi (NA)

Division of Hematology/Oncology, Columbia University Medical Center, New York, NY.

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Classifications MeSH