The Association of Improved Overall Survival with NSAIDs in Non-Small Cell Lung Cancer Patients Receiving Immune Checkpoint Inhibitors

Nikhil T Sebastian; William A Stokes; Madhusmita Behera; Renjian Jiang; David A Gutman; Zhonglu Huang; Abigail Burns; Vidula Sukhatme; Michael C Lowe; Suresh S Ramalingam; Vikas P Sukhatme; Drew Moghanaki

doi:10.1016/j.cllc.2022.12.013

The Association of Improved Overall Survival with NSAIDs in Non-Small Cell Lung Cancer Patients Receiving Immune Checkpoint Inhibitors

Clin Lung Cancer. 2023 May;24(3):287-294. doi: 10.1016/j.cllc.2022.12.013. Epub 2023 Jan 21.

Authors

Affiliations

¹ Department of Radiation Oncology, Emory University, Atlanta, GA; Winship Cancer Institute, Emory University, Atlanta, GA. Electronic address: Nikhil.Sebastian@emory.edu.
² Department of Radiation Oncology, Emory University, Atlanta, GA; Winship Cancer Institute, Emory University, Atlanta, GA.
³ Winship Cancer Institute, Emory University, Atlanta, GA.
⁴ Winship Cancer Institute, Emory University, Atlanta, GA; Atlanta Veterans Affairs Health Care System, Decatur, GA.
⁵ Atlanta Veterans Affairs Health Care System, Decatur, GA.
⁶ Morningside Center for Innovative and Affordable Medicine, Emory University, Atlanta, GA; GlobalCures, Inc, Newton, MA.
⁷ Morningside Center for Innovative and Affordable Medicine, Emory University, Atlanta, GA; Division of Surgical Oncology, Emory University, Atlanta, GA.
⁸ Winship Cancer Institute, Emory University, Atlanta, GA; Department of Hematology and Medical Oncology, Emory University, Atlanta, GA.
⁹ Morningside Center for Innovative and Affordable Medicine, Emory University, Atlanta, GA.
¹⁰ Department of Radiation Oncology, University of California Los Angeles, Los Angeles, CA.

PMID: 36804711
DOI: 10.1016/j.cllc.2022.12.013

Abstract

Background: Immune checkpoint inhibitors (ICI) are commonly used in the management of patients with advanced non-small cell lung cancer (NSCLC), but response is suboptimal. Preclinical data suggest ICI efficacy may be enhanced with concomitant nonsteroidal anti-inflammatory (NSAID) medications.

Patients and methods: In this retrospective study, the Veterans Health Administration Corporate Data Warehouse was queried for patients diagnosed with NSCLC and treated with ICI from 2010 to 2018. Concomitant NSAID use was defined as NSAID dispensation by a VA pharmacy within 90 days of the any ICI infusion. To mitigate immortal time bias, patients who started NSAIDs 60 or more days after ICI initiation were excluded from analysis. Survival was measured from start of ICI.

Results: We identified 3634 patients with NSCLC receiving ICI; 2336 (64.3%) were exposed to concomitant NSAIDs. On multivariable analysis, NSAIDs were associated with better overall survival (HR = 0.90; 95% CI, 0.83-0.98; P = .010). When stratifying by NSAID type, diclofenac was the only NSAID with significant association with overall survival (HR = 0.75; 95% CI, 0.68-0.83; P < .001). Propensity score matching of the original cohort yielded 1251 patients per cohort balanced in characteristics. NSAIDs remained associated with improved overall survival (HR = 0.85; 95% CI, 0.78-0.92; P < .001).

Conclusion: This study of Veterans with NSCLC treated with ICI demonstrated that concomitant NSAIDs are associated with longer OS. This may indicate that NSAIDs can enhance ICI-induced antitumor immunity and should prospectively validated.

Keywords: Immunotherapy; Metastatic; NSCLC; Nonsteroidal anti-inflammatory drugs; Veterans.

Publication types

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

MeSH terms

Anti-Inflammatory Agents, Non-Steroidal / therapeutic use
Carcinoma, Non-Small-Cell Lung* / drug therapy
Humans
Immune Checkpoint Inhibitors / therapeutic use
Lung Neoplasms* / drug therapy
Retrospective Studies

Substances

Anti-Inflammatory Agents, Non-Steroidal
Immune Checkpoint Inhibitors