NSAID Use with Immune Checkpoint Inhibitors Associated with Longer Overall Survival in NSCLC

Lung cancer is a leading cause of global cancer mortality, with non–small-cell lung cancer (NSCLC) accounting for 85% of all lung cancers.¹ Fifty percent of patients with NSCLC already have stage IV metastatic disease at their diagnosis.¹ Locally advanced disease (stage III) is found in 30% of newly diagnosed NSCLC patients, with 20% having stage I or II localized disease.¹ The 5-year overall survival (OS) for patients with NSCLC varies with stage, with decreasing OS rates occurring in more advanced cases at diagnosis.¹ Immune checkpoint inhibitors (ICIs), a type of immunotherapy, are an effective option for treatment of patients with metastatic NSCLC with improved response rates, OS, and better tolerability when compared with chemotherapy.¹ ICIs work by harnessing the body’s autoimmune functions to block the immunosuppressive effect of cancer cells.² When ICIs are combined with chemotherapy, improved survival has been reported.² Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely used for anti-inflammatory and analgesic effects for a wide variety of diseases and conditions, including cancer.³

At the 2021 American Society of Clinical Oncology Annual Meeting, data were released from a retrospective cohort study on Veterans Administration patients with NSCLC who were treated with ICIs and NSAIDs between 2010 and 2018. The study aimed to determine if the use of NSAIDs along with ICIs would enhance the efficacy of ICIs and improve OS. There were 3145 patients with NSCLC who were treated with ICIs during the study period, and 2336 of these patients were exposed to NSAIDs.⁴ Most (97%) patients were male with a median age of 69 years.⁴ The majority (73%) of patients were white and 21% were black, with 66% of the patients living in an urban area.⁴ At initial diagnosis, 68% of patients had stage III or stage IV disease, with 48% of these patients having adenocarcinoma and 38% having squamous-cell NSCLC.⁴ Comorbidities were found in 60% of the patients.⁴

When treatment outcomes were evaluated, the researchers found that 54% of patients had chemotherapy prior to receiving ICIs, whereas 31% had chemotherapy at the same time that ICIs were given.⁴ Investigation of concomitant NSAID use revealed that the most frequently used NSAIDs were aspirin (35%), ketorolac (11%), and ibuprofen (7%), and that 44% of the patients were exposed to >1 NSAID.⁴ It was found that exposure to >1 NSAID was associated with a longer OS.⁴ In addition, other factors contributing to OS included use of chemotherapy after ICI, concurrent chemotherapy during ICI, black race, female gender, younger age, and adenocarcinoma histology.

This study demonstrated that patients with NSCLC who were treated with ICIs and exposed to NSAIDs had a longer OS.

References

1. Vansteenkiste J, Wauters E, Reymen B, et al. Current status of immune checkpoint inhibition in early-stage NSCLC. Ann Oncol. 2019;30:1244-1253.
2. Onoi K, Chihara Y, Uchino J, et al. Immune checkpoint inhibitors for lung cancer treatment: a review. J Clin Med. 2020;9:1362.
3. Ghlichloo I, Gerriets V. Nonsteroidal Anti-Inflammatory Drugs (NSAIDs). Treasure Island, FL: StatPearls Publishing; May 12, 2021. www.ncbi.nlm.nih.gov/books/NBK547742. Accessed July 12, 2021.
4. Moghanaki D, Stokes W, Behera M, et al. Association of concomitant NSAID and immunotherapy on outcomes in patients with non-small cell lung cancer: analysis of the National Veterans Health Administration database. J Clin Oncol. 2021;39(suppl 15):9107.