The value of innovation: association between improvements in survival of advanced and metastatic non-small cell lung cancer and targeted and immunotherapy.


Journal

BMC medicine
ISSN: 1741-7015
Titre abrégé: BMC Med
Pays: England
ID NLM: 101190723

Informations de publication

Date de publication:
15 09 2021
Historique:
received: 30 04 2021
accepted: 22 07 2021
entrez: 15 9 2021
pubmed: 16 9 2021
medline: 16 10 2021
Statut: epublish

Résumé

Significant improvements in mortality among patients with non-small cell lung cancer (NSCLC) in the USA over the past two decades have been reported based on Surveillance, Epidemiology, and End Results (SEER) data. The timing of these improvements led to suggestions that they result from the introduction of new treatments; however, few studies have directly investigated this. The aim of this study was to investigate the extent to which population level improvements in survival of advanced and/or metastatic NSCLC (admNSCLC) patients were associated with changes in treatment patterns. We utilized a de-identified database to select three cohorts of patients with admNSCLC: (1) patients with non-oncogene (EGFR/ALK/ROS1/BRAF) positive tumors, (2) patients with ALK-positive (ALK+) tumors, and (3) patients with EGFR-positive (EGFR+) tumors. All patients were diagnosed with admNSCLC between 2012 and 2019. Multivariable Cox models adjusting for baseline characteristics and receipt of targeted and immunotherapy were utilized to explore the relationship between these variables and changes in the hazard of death by calendar year in each cohort. We included 28,154 admNSCLC patients with non-oncogene positive tumors, 598 with ALK+ tumors, and 2464 with EGFR+ tumors eligible for analysis. After adjustment for differences in baseline characteristics, the hazard of death in patients who had non-oncogene positive tumors diagnosed in 2015, 2016, 2017, 2018 ,and 2019 was observed to be 12%, 11%, 17%, 20%, and 21% lower respectively than that for those diagnosed in 2012. Upon additionally adjusting for receipt of first line or second line immunotherapy, the decrease in the hazard of death by calendar year was no longer observed, suggesting improvements in survival observed over time may be explained by the introduction of these treatments. Similarly, decreases in the hazard of death were only observed in patients with ALK+ tumors diagnosed between 2017 and 2019 relative to 2012 but were no longer observed following adjustment for the use of 1st and later generation ALK inhibitors. Among patients with EGFR+ tumors, the hazard of death did not improve significantly over time. Our findings expand on the SEER data and provide additional evidence suggesting improvements in survival of patients with advanced and metastatic NSCLC over the past decade could be explained by the change in treatment patterns over this period.

Sections du résumé

BACKGROUND
Significant improvements in mortality among patients with non-small cell lung cancer (NSCLC) in the USA over the past two decades have been reported based on Surveillance, Epidemiology, and End Results (SEER) data. The timing of these improvements led to suggestions that they result from the introduction of new treatments; however, few studies have directly investigated this. The aim of this study was to investigate the extent to which population level improvements in survival of advanced and/or metastatic NSCLC (admNSCLC) patients were associated with changes in treatment patterns.
METHODS
We utilized a de-identified database to select three cohorts of patients with admNSCLC: (1) patients with non-oncogene (EGFR/ALK/ROS1/BRAF) positive tumors, (2) patients with ALK-positive (ALK+) tumors, and (3) patients with EGFR-positive (EGFR+) tumors. All patients were diagnosed with admNSCLC between 2012 and 2019. Multivariable Cox models adjusting for baseline characteristics and receipt of targeted and immunotherapy were utilized to explore the relationship between these variables and changes in the hazard of death by calendar year in each cohort.
RESULTS
We included 28,154 admNSCLC patients with non-oncogene positive tumors, 598 with ALK+ tumors, and 2464 with EGFR+ tumors eligible for analysis. After adjustment for differences in baseline characteristics, the hazard of death in patients who had non-oncogene positive tumors diagnosed in 2015, 2016, 2017, 2018 ,and 2019 was observed to be 12%, 11%, 17%, 20%, and 21% lower respectively than that for those diagnosed in 2012. Upon additionally adjusting for receipt of first line or second line immunotherapy, the decrease in the hazard of death by calendar year was no longer observed, suggesting improvements in survival observed over time may be explained by the introduction of these treatments. Similarly, decreases in the hazard of death were only observed in patients with ALK+ tumors diagnosed between 2017 and 2019 relative to 2012 but were no longer observed following adjustment for the use of 1st and later generation ALK inhibitors. Among patients with EGFR+ tumors, the hazard of death did not improve significantly over time.
CONCLUSION
Our findings expand on the SEER data and provide additional evidence suggesting improvements in survival of patients with advanced and metastatic NSCLC over the past decade could be explained by the change in treatment patterns over this period.

Identifiants

pubmed: 34521405
doi: 10.1186/s12916-021-02070-w
pii: 10.1186/s12916-021-02070-w
pmc: PMC8442434
doi:

Substances chimiques

Proto-Oncogene Proteins 0
Protein-Tyrosine Kinases EC 2.7.10.1

Types de publication

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

Langues

eng

Sous-ensembles de citation

IM

Pagination

209

Subventions

Organisme : NCATS NIH HHS
ID : UL1 TR003167
Pays : United States

Informations de copyright

© 2021. The Author(s).

Références

N Engl J Med. 2020 Aug 13;383(7):640-649
pubmed: 32786189
Stat Med. 2009 Aug 30;28(19):2473-89
pubmed: 19472308
Immune Netw. 2020 Jan 27;20(1):e10
pubmed: 32158598
J Hematol Oncol. 2020 Oct 27;13(1):143
pubmed: 33109256
J Med Econ. 2020 Dec;23(12):1558-1569
pubmed: 33161782
Cancers (Basel). 2020 Mar 20;12(3):
pubmed: 32245016
JAMA. 2019 Apr 9;321(14):1391-1399
pubmed: 30964529

Auteurs

Sreeram Ramagopalan (S)

F. Hoffmann-La Roche Ltd, Grenzacherstrasse 124, 4070, Basel, Switzerland. sreeram.ramagopalan@roche.com.

Thomas P Leahy (TP)

PHMR Ltd., Westport, Ireland.

Joshua Ray (J)

F. Hoffmann-La Roche Ltd, Grenzacherstrasse 124, 4070, Basel, Switzerland.

Samantha Wilkinson (S)

Roche Products Ltd, Welwyn Garden City, UK.

Cormac Sammon (C)

PHMR Ltd., Westport, Ireland.

Vivek Subbiah (V)

Department of Investigational Cancer Therapeutics, Division of Cancer Medicine, UT MD Anderson Cancer Center, Houston, USA.
MD Anderson Cancer Network, UT MD Anderson Cancer Center, Houston, USA.
Clinical Center For Targeted Therapy, UT MD Anderson Cancer Center, Houston, USA.
Division of Pediatrics, UT MD Anderson Cancer Center, Houston, USA.

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Classifications MeSH