Durvalumab therapy following chemoradiation compared with a historical cohort treated with chemoradiation alone in patients with stage III non-small cell lung cancer: A real-world multicentre study.


Journal

European journal of cancer (Oxford, England : 1990)
ISSN: 1879-0852
Titre abrégé: Eur J Cancer
Pays: England
ID NLM: 9005373

Informations de publication

Date de publication:
01 2021
Historique:
received: 28 05 2020
revised: 30 09 2020
accepted: 08 10 2020
pubmed: 27 11 2020
medline: 24 4 2021
entrez: 26 11 2020
Statut: ppublish

Résumé

The PACIFIC trial demonstrated that durvalumab therapy following chemoradiation (CRT) was associated with improved overall survival (OS) in patients with stage III non-small cell lung cancer (NSCLC). It is unclear whether the results obtained as part of randomised controlled trials are a reflection of real-world (RW) data. Several questions remain unanswered with regard to RW durvalumab use, such as optimal time to durvalumab initiation, incidence of pneumonitis and response in PD-L1 subgroups. In this multicentre retrospective analysis, 147 patients with stage III NSCLC treated with CRT followed by durvalumab were compared with a historical cohort of 121 patients treated with CRT alone. Survival curves were estimated using the Kaplan-Meier method and compared with the log-rank test in univariate analysis. Multivariate analysis was performed to evaluate the effect of standard prognostic factors for durvalumab use. Median OS was not reached in the durvalumab group, compared with 26.9 months in the historical group (hazard ratio [HR]: 0.56, 95% confidence interval [CI]: 0.37-0.85, p = 0.001). In the durvalumab group, our data suggest improved 12-month OS in patients with PD-L1 expression ≥50% (100% vs 86%, HR: 0.25, 95% CI: 0.11-0.58, p = 0.007). There was no difference in OS between patients with a PD-L1 expression of 1-49% and patients with PD-L1 expression <1%. Delay in durvalumab initiation beyond 42 days did not impact OS. Incidence of pneumonitis was similar in the durvalumab and historical groups. In the durvalumab group, patients who experienced any-grade pneumonitis had a lower 12-month OS than patients without pneumonitis (85% vs 95%, respectively; HR: 3.3, 95% CI: 1.2-9.0, p = 0.006). This multicentre analysis suggests that PD-L1 expression ≥50% was associated with favourable OS in patients with stage III NSCLC treated with durvalumab after CRT, whereas the presence of pneumonitis represented a negative prognostic factor.

Sections du résumé

BACKGROUND
The PACIFIC trial demonstrated that durvalumab therapy following chemoradiation (CRT) was associated with improved overall survival (OS) in patients with stage III non-small cell lung cancer (NSCLC). It is unclear whether the results obtained as part of randomised controlled trials are a reflection of real-world (RW) data. Several questions remain unanswered with regard to RW durvalumab use, such as optimal time to durvalumab initiation, incidence of pneumonitis and response in PD-L1 subgroups.
METHODS
In this multicentre retrospective analysis, 147 patients with stage III NSCLC treated with CRT followed by durvalumab were compared with a historical cohort of 121 patients treated with CRT alone. Survival curves were estimated using the Kaplan-Meier method and compared with the log-rank test in univariate analysis. Multivariate analysis was performed to evaluate the effect of standard prognostic factors for durvalumab use.
RESULTS
Median OS was not reached in the durvalumab group, compared with 26.9 months in the historical group (hazard ratio [HR]: 0.56, 95% confidence interval [CI]: 0.37-0.85, p = 0.001). In the durvalumab group, our data suggest improved 12-month OS in patients with PD-L1 expression ≥50% (100% vs 86%, HR: 0.25, 95% CI: 0.11-0.58, p = 0.007). There was no difference in OS between patients with a PD-L1 expression of 1-49% and patients with PD-L1 expression <1%. Delay in durvalumab initiation beyond 42 days did not impact OS. Incidence of pneumonitis was similar in the durvalumab and historical groups. In the durvalumab group, patients who experienced any-grade pneumonitis had a lower 12-month OS than patients without pneumonitis (85% vs 95%, respectively; HR: 3.3, 95% CI: 1.2-9.0, p = 0.006).
CONCLUSIONS
This multicentre analysis suggests that PD-L1 expression ≥50% was associated with favourable OS in patients with stage III NSCLC treated with durvalumab after CRT, whereas the presence of pneumonitis represented a negative prognostic factor.

Identifiants

pubmed: 33242835
pii: S0959-8049(20)31067-4
doi: 10.1016/j.ejca.2020.10.008
pii:
doi:

Substances chimiques

Antibodies, Monoclonal 0
Antineoplastic Agents, Immunological 0
durvalumab 28X28X9OKV

Types de publication

Journal Article Multicenter Study Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

83-91

Informations de copyright

Copyright © 2020 Elsevier Ltd. All rights reserved.

Déclaration de conflit d'intérêts

Conflict of interest statement B.R., H.B. and A.E. report grant support from AstraZeneca. The additional authors have no conflict of interest to declare.

Auteurs

Antoine Desilets (A)

Centre de Recherche Du Centre Hospitalier de L'Université de Montréal (CRCHUM), 900, Rue Saint-Denis, Pavillon R, H2X 0A9, Montreal, Quebec, Canada; Department of Hematology and Oncology, Centre Hospitalier de L'Université de Montréal (CHUM), 1051, Rue Sanguinet, H2X 3E4, Montreal, Quebec, Canada. Electronic address: antoine.desilets@umontreal.ca.

Félix Blanc-Durand (F)

Centre de Recherche Du Centre Hospitalier de L'Université de Montréal (CRCHUM), 900, Rue Saint-Denis, Pavillon R, H2X 0A9, Montreal, Quebec, Canada; Department of Hematology and Oncology, Centre Hospitalier de L'Université de Montréal (CHUM), 1051, Rue Sanguinet, H2X 3E4, Montreal, Quebec, Canada. Electronic address: felix.blancdurand@gmail.com.

Sally Lau (S)

Princess Margaret Cancer Centre, University Health Network (UNH), 610 University Ave, M5G 2C1, Toronto, Ontario, Canada. Electronic address: sally.lau@uhn.ca.

Taiki Hakozaki (T)

Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital, 3-18-22 Honkomagome, 113-8677, Bunkyo City, Tokyo, Japan. Electronic address: t-hakozaki@cick.jp.

Rui Kitadai (R)

Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital, 3-18-22 Honkomagome, 113-8677, Bunkyo City, Tokyo, Japan. Electronic address: rkitadai@cick.jp.

Julie Malo (J)

Centre de Recherche Du Centre Hospitalier de L'Université de Montréal (CRCHUM), 900, Rue Saint-Denis, Pavillon R, H2X 0A9, Montreal, Quebec, Canada. Electronic address: julie.malo.chum@ssss.gouv.qc.ca.

Wiam Belkaid (W)

Centre de Recherche Du Centre Hospitalier de L'Université de Montréal (CRCHUM), 900, Rue Saint-Denis, Pavillon R, H2X 0A9, Montreal, Quebec, Canada. Electronic address: wiam.belkaid.chum@ssss.gouv.qc.ca.

Corentin Richard (C)

Centre de Recherche Du Centre Hospitalier de L'Université de Montréal (CRCHUM), 900, Rue Saint-Denis, Pavillon R, H2X 0A9, Montreal, Quebec, Canada. Electronic address: corentin.richard@umontreal.ca.

Meriem Messaoudene (M)

Centre de Recherche Du Centre Hospitalier de L'Université de Montréal (CRCHUM), 900, Rue Saint-Denis, Pavillon R, H2X 0A9, Montreal, Quebec, Canada. Electronic address: meriem.messaoudene@umontreal.ca.

Lena Cvetkovic (L)

Department of Hematology and Oncology, Centre Hospitalier de L'Université de Montréal (CHUM), 1051, Rue Sanguinet, H2X 3E4, Montreal, Quebec, Canada. Electronic address: lena.cvetkovic@umontreal.ca.

Suzanne Kazandjian (S)

Department of Hematology and Oncology, Centre Hospitalier de L'Université de Montréal (CHUM), 1051, Rue Sanguinet, H2X 3E4, Montreal, Quebec, Canada. Electronic address: suzanne.kazandjian@mail.mcgill.ca.

Mustapha Tehfe (M)

Department of Hematology and Oncology, Centre Hospitalier de L'Université de Montréal (CHUM), 1051, Rue Sanguinet, H2X 3E4, Montreal, Quebec, Canada. Electronic address: mustapha.tehfe.chum@ssss.gouv.qc.ca.

Marie Florescu (M)

Department of Hematology and Oncology, Centre Hospitalier de L'Université de Montréal (CHUM), 1051, Rue Sanguinet, H2X 3E4, Montreal, Quebec, Canada. Electronic address: marie.florescu.chum@ssss.gouv.qc.ca.

Kevin Jao (K)

Department of Hematology and Oncology, Hôpital Du Sacré Coeur de Montréal, 5400, Boulevard Gouin Ouest, H4J 1C5, Montreal, Quebec, Canada. Electronic address: kevin.jao@umontreal.ca.

Nathalie Daaboul (N)

Integrated Cancer Center, Charles-Le-Moyne Hospital, 3120, Boulevard Taschereau, J4V 2H1, Greenfield Park, Quebec, Canada. Electronic address: nathalie.daaboul@usherbrooke.ca.

Scott Owen (S)

Cedars Cancer Center, McGill University Healthcare Center (MUHC), 1001, Boulevard Décarie, H4A 3J1, Montreal, Quebec, Canada. Electronic address: scott.owen@mcgill.ca.

Benjamin Shieh (B)

Cedars Cancer Center, McGill University Healthcare Center (MUHC), 1001, Boulevard Décarie, H4A 3J1, Montreal, Quebec, Canada. Electronic address: benjamin.shieh@mcgill.ca.

Jason Agulnik (J)

Segal Cancer Center, Jewish General Hospital, 3755, Chemin de La Côte-Sainte-Catherine, H3T 1E2, Montreal, Quebec, Canada. Electronic address: jagulnik@jgh.mcgill.ca.

Victor Cohen (V)

Segal Cancer Center, Jewish General Hospital, 3755, Chemin de La Côte-Sainte-Catherine, H3T 1E2, Montreal, Quebec, Canada. Electronic address: vcohen@jgh.mcgill.ca.

Chloé Charbonneau (C)

Department of Hematology and Oncology, Centre Hospitalier de L'Université de Québec (CHUQ), 11, Côte Du Palais, G1R 2J6, Quebec City, Quebec, Canada. Electronic address: chloe.charbonneau.1@ulaval.ca.

Nicolas Marcoux (N)

Department of Hematology and Oncology, Centre Hospitalier de L'Université de Québec (CHUQ), 11, Côte Du Palais, G1R 2J6, Quebec City, Quebec, Canada. Electronic address: nicolas.marcoux.1@ulaval.ca.

Normand Blais (N)

Department of Hematology and Oncology, Centre Hospitalier de L'Université de Montréal (CHUM), 1051, Rue Sanguinet, H2X 3E4, Montreal, Quebec, Canada. Electronic address: normand.blais.chum@ssss.gouv.qc.ca.

Natasha B Leighl (NB)

Princess Margaret Cancer Centre, University Health Network (UNH), 610 University Ave, M5G 2C1, Toronto, Ontario, Canada. Electronic address: natasha.leighl@uhn.ca.

Penelope A Bradbury (PA)

Princess Margaret Cancer Centre, University Health Network (UNH), 610 University Ave, M5G 2C1, Toronto, Ontario, Canada. Electronic address: penelope.bradbury@uhn.ca.

Geoffrey Liu (G)

Princess Margaret Cancer Centre, University Health Network (UNH), 610 University Ave, M5G 2C1, Toronto, Ontario, Canada. Electronic address: geoffrey.liu@uhn.ca.

Frances A Shepherd (FA)

Princess Margaret Cancer Centre, University Health Network (UNH), 610 University Ave, M5G 2C1, Toronto, Ontario, Canada. Electronic address: frances.shepherd@uhn.ca.

Houda Bahig (H)

Centre de Recherche Du Centre Hospitalier de L'Université de Montréal (CRCHUM), 900, Rue Saint-Denis, Pavillon R, H2X 0A9, Montreal, Quebec, Canada; Department of Hematology and Oncology, Centre Hospitalier de L'Université de Montréal (CHUM), 1051, Rue Sanguinet, H2X 3E4, Montreal, Quebec, Canada. Electronic address: houda.bahig.chum@ssss.gouv.qc.ca.

Bertrand Routy (B)

Centre de Recherche Du Centre Hospitalier de L'Université de Montréal (CRCHUM), 900, Rue Saint-Denis, Pavillon R, H2X 0A9, Montreal, Quebec, Canada; Department of Hematology and Oncology, Centre Hospitalier de L'Université de Montréal (CHUM), 1051, Rue Sanguinet, H2X 3E4, Montreal, Quebec, Canada. Electronic address: bertrand.routy@umontreal.ca.

Adrian Sacher (A)

Princess Margaret Cancer Centre, University Health Network (UNH), 610 University Ave, M5G 2C1, Toronto, Ontario, Canada. Electronic address: adrian.sacher@uhn.ca.

Arielle Elkrief (A)

Centre de Recherche Du Centre Hospitalier de L'Université de Montréal (CRCHUM), 900, Rue Saint-Denis, Pavillon R, H2X 0A9, Montreal, Quebec, Canada; Cedars Cancer Center, McGill University Healthcare Center (MUHC), 1001, Boulevard Décarie, H4A 3J1, Montreal, Quebec, Canada; Segal Cancer Center, Jewish General Hospital, 3755, Chemin de La Côte-Sainte-Catherine, H3T 1E2, Montreal, Quebec, Canada. Electronic address: arielle.elkrief@mail.mcgill.ca.

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