NSAID Use May Improve OS During Chemoradiation for Patients with HNSCC

A study published in JAMA Network Open suggested a possible advantage in overall survival (OS) for patients taking nonsteroidal anti-inflammatory drugs (NSAIDs) during chemoradiation for head and neck squamous cell carcinoma (HNSCC).

However, researchers suggested that future studies evaluating this association are warranted.

“This large, retrospective cohort study suggests a significant association with improved OS for patients with HNSCC taking NSAIDs during definitive CRT,” the authors wrote. “While the change in LC with NSAID use was not significant, future studies should continue to evaluate this possibility.”

Overall, 460 patients with HNSCC who were treated with chemoradiation therapy (CRT) at a single institution between January 1, 2005 and August 1, 2017 were included in the study, including 201 patients (43.7%) who were taking NSAIDs during treatment. Patient and tumor characteristics included age, race/ethnicity, smoking status, alcohol use, comorbidities (respiratory, cardiovascular, immune, renal, endocrine), disease stage, human papillomavirus (HPV) status, and treatment duration.

On univariate analysis, NSAID use (hazard ratio [HR], 0.63; 95% CI, 0.43-0.92; P = 0.02) was associated with better OS. Moreover, on Cox regression analysis, after backward selection adjustment for possibly confounding factors such as age, smoking status, primary tumor site, human papillomavirus status, diabetes, stroke, and hyperlipidemia, NSAID use continued to be significantly associated with better OS (HR, 0.59; 95% CI, 0.38-0.90; P = 0.02).

Even further, at 5 years NSAID use was associated with significantly better OS compared with those who did not take concurrent NSAIDs (63.6% [56 of 88 patients]; 95% CI, 58%-73% vs 56.1% [83 of 148 patients]; 95% CI, 50%-63%; P = 0.03).

However, NSAID use was not associated with better disease-specific survival (DSS) in univariate (HR, 0.82; 95% CI, 0.48-1.41; P = 0.47) or multivariate (HR, 0.98; 95% CI, 0.57-1.70; P = 0.44) analysis. NSAID use was also not associated with better response to treatment (HR, 1.44; 95% CI, 0.91-2.27; P = 0.12) or distant failure (HR, 1.12; 95% CI, 0.68-1.84; P = 0.65). Furthermore, change in local control with NSAID use was not found to be statistically significant (HR, 0.59; 95% CI, 0.31-1.10; P = 0.10).

“This suggests the observed survival advantage may be associated with the cardiovascular benefits of NSAIDs rather than any chemoprotective properties they may have, particularly because there was a higher proportion of patients with diabetes and coronary artery disease in the group taking NSAIDs,” the authors wrote. “This is increasingly important because the risk of noncancer death now surpasses that of cancer death, with heart disease being the leading cause of noncancer mortality.”

“The fact that anticoagulants were not associated with improved OS while NSAIDs were suggests that the cyclooxygenase mechanism may be a contributing factor to survival,” the authors continued. “This mechanism may be a combination of local recurrence reduction through cyclooxygenase inhibition and treatment of underlying cardiovascular disease.”

Prior research has suggested that PIK3CA variations may be a clinically useful marker to identify which patients with HNSCC will benefit from NSAID use; however, the investigators suggested that until such testing is routine, the current data indicates that giving daily aspirin to patients with HNSCC who are receiving CRT may be associated with improved survival.

Notably, though the researchers had access to patient comorbidity data, they did not have access to the reason why patients were prescribed regular NSAID use, nor were they aware of the duration of use. However, the majority of patients who were taking NSAIDs at the time of consultation noted that they were taking a “baby” (81-mg) aspirin, which was continued during CRT.

Reference:

Iovoli AJ, Hermann GM, Ma SJ, et al. Association of Nonsteroidal Anti-inflammatory Drug Use With Survival in Patients With Squamous Cell Carcinoma of the Head and Neck Treated With Chemoradiation Therapy. JAMA Network Open.