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 cases.¹ Fifty percent of NSCLC patients have stage IV metastatic disease at diagnosis.¹ Locally advanced disease (stage III) is found in 30% of newly diagnosed patients, with 20% having stage I or II localized disease.¹ The 5-year overall survival (OS) of NSCLC varies with stage, with decreasing OS rates occurring in more advanced cases at diagnosis.¹ Immune checkpoint inhibition (ICI) immunotherapy is an effective option for treatment of metastatic NSCLC with improved response rates and OS and better tolerability when compared with chemotherapy.¹ ICI works by harnessing the body’s autoimmune functions to block the immunosuppressive effect of cancer cells.² When ICI is combined with chemotherapy, improved survival has also 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 virtual 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 ICI and NSAID medications between 2010 and 2018. The study aimed to determine if the use of NSAIDs along with ICI would enhance the efficacy of ICI and improve OS. There were 3145 patients with NSCLC who were treated with ICI during the study period, and 2336 of these patients were exposed to NSAIDs.⁴ Most patients (97%) were male with a median age of 69 years.⁴ The majority of patients were white (73%) and 21% were black, with 66% of the patients living in an urban area.⁴ At initial diagnosis, most patients had stage III or IV disease (68%) 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 the patients had chemotherapy prior to ICI while 31% had chemotherapy at the same time as ICI was given.⁴ Investigation of concomitant NSAID use revealed that the most commonly 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 ICI 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). National Center for Biotechnology Information StatPearls. Updated 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.