Real-world Studies Link NSAID Use to Improved Overall Lung Cancer Survival

Author:

Roszik Jason12ORCID,Lee J. Jack3ORCID,Wu Yi-Hung3,Liu Xi45,Kawakami Masanori45ORCID,Kurie Jonathan M.4,Belouali Anas6,Boca Simina M.67ORCID,Gupta Samir6ORCID,Beckman Robert A.6ORCID,Madhavan Subha67,Dmitrovsky Ethan458ORCID

Affiliation:

1. 1Departments of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas.

2. 2Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.

3. 3Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, Texas.

4. 4Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.

5. 5Frederick National Laboratory for Cancer Research, Frederick, Maryland.

6. 6Georgetown Lombardi Comprehensive Cancer Center and Innovation Center for Biomedical Informatics, Georgetown University Medical Center, Washington, District of Columbia.

7. 7AstraZeneca, Gaithersburg, Maryland.

8. 8Cancer Biology The University of Texas MD Anderson Cancer Center, Houston, Texas.

Abstract

Inflammation is a cancer hallmark. NSAIDs improve overall survival (OS) in certain cancers. Real-world studies explored here whether NSAIDs improve non–small cell lung cancer (NSCLC) OS. Analyses independently interrogated clinical databases from The University of Texas MD Anderson Cancer Center (MDACC cohort, 1987 to 2015; 33,162 NSCLCs and 3,033 NSAID users) and Georgetown-MedStar health system (Georgetown cohort, 2000 to 2019; 4,497 NSCLCs and 1,993 NSAID users). Structured and unstructured clinical data were extracted from electronic health records using natural language processing (NLP). Associations were made between NSAID use and NSCLC prognostic features (tobacco use, gender, race, and body mass index, BMI). NSAIDs were statistically significantly (P < 0.0001) associated with increased NSCLC survival (5-year OS 29.7% for NSAID users vs. 13.1% for nonusers) in the MDACC cohort. NSAID users gained 11.6 months over nonusers in 5-year restricted mean survival time. Stratified analysis by stage, histopathology, and multicovariable assessment substantiated benefits. NSAID users were pooled independent of NSAID type and by NSAID type. Landmark analysis excluded immortal time bias. Survival improvements (P < 0.0001) were confirmed in the Georgetown cohort. Thus, real-world NSAID usage was independently associated with increased NSCLC survival in the MDACC and Georgetown cohorts. Findings were confirmed by landmark analyses and NSAID type. The OS benefits persisted despite tobacco use and did not depend on gender, race, or BMI (MDACC cohort, P < 0.0001). These real-world findings could guide future NSAID lung cancer randomized trials. Significance: NLP and real-world studies conducted in large cohorts explored whether NSAIDs improved survival across NSCLC stages, histopathology, gender, smoking history, or demographic groups. A statistically significant association between NSAID use and NSCLC survival was found. This provides a rationale for future NSAID randomized NSCLC trials.

Funder

HHS | National Institutes of Health

Samuel Waxman Cancer Research Foundation

University of Texas System

American Cancer Society

Publisher

American Association for Cancer Research (AACR)

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