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

• Published in: Clinical lung cancer 2023-05, Vol.24 (3), p.287-294
• Main Authors: Sebastian, Nikhil T., Stokes, William A., Behera, Madhusmita, Jiang, Renjian, Gutman, David A., Huang, Zhonglu, Burns, Abigail, Sukhatme, Vidula, Lowe, Michael C., Ramalingam, Suresh S., Sukhatme, Vikas P., Moghanaki, Drew
• Format: Article
• Language: English
• Subjects: Anti-Inflammatory Agents, Non-Steroidal - therapeutic use; Carcinoma, Non-Small-Cell Lung - drug therapy; Humans; Immune Checkpoint Inhibitors - therapeutic use; Immunotherapy; Lung Neoplasms - drug therapy; Metastatic; Nonsteroidal anti-inflammatory drugs; NSCLC; Retrospective Studies; Veterans
• ISSN: 1525-7304; 1938-0690
• DOI: 10.1016/j.cllc.2022.12.013

•Patients on immune checkpoint inhibitors had improved survival when taking nonsteroidal anti-inflammatory (NSAIDs).•Diclofenac has strongest association with overall survival.•Concomitant NSAIDs may improve Immune checkpoint inhibitors (ICI) efficacy, but this requires further study. 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. 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. 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). 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. Response rates of immune checkpoint inhibitors (ICI) in advanced non-small cell lung cancer are suboptimal. In this retrospective cohort study of over 3,600 Veterans with advanced or metastatic non–small cell lung cancer, concomitant use of NSAIDs was associated with improved survival when given with ICI. This may indicate possibility of enhancing ICI efficacy using concomitant NSAIDs, although requires validation.