NSAIDs may confer survival advantage for HNSCC patients undergoing CRT

In individuals undergoing definitive chemoradiotherapy (CRT) for head and neck squamous cell carcinoma (HNSCC), the use of NSAIDs was associated with a significantly better overall survival (OS), a study has shown.

NSAIDs apparently have chemotherapeutic potential, owing to their influence on cyclo-oxygenase inhibition, with evidence reflecting a survival advantage for colorectal cancer and other cancer histologies. [Carcinogenesis 2009;30:377-386; Lancet Oncol 2012;13:518-527] “This cohort study suggests a possible OS advantage for patients taking NSAIDs during CRT for HNSCC,” said the researchers.

Using a large, single-institution HNSCC database, the team evaluated 460 individuals with HNSCC (median age 60 years, 82 percent male) to explore survival outcomes tied to NSAID use during CRT. Of these, 43.7 percent were taking NSAIDs*. Median follow-up was 4 years. [JAMA Network Open 2020;3:e207199]

After adjusting for potential confounders**, multivariate analysis showed a significant association between NSAID use and better OS (hazard ratio [HR], 0.59; p=0.02). This association remained even after excluding nasopharyngeal cancer and unknown primary tumours in both univariate (HR, 0.67; p=0.01) and multivariate analyses (HR, 0.62; p=0.04).

Five-year outcomes demonstrated a significantly better OS with vs without concomitant NSAID use (63.6 percent vs 56.1 percent; p=0.03).

“[The OS improvements] suggest that the cyclo-oxygenase mechanism may be a contributing factor to survival. This mechanism may be a combination of local recurrence reduction through cyclo-oxygenase inhibition and treatment of underlying cardiovascular disease,” said the researchers.

The lack of reduction in distant metastasis among those taking NSAIDs may also explain for the improved OS, as proposed by previous studies. [Lancet Oncol 2009;10:501-507; Lancet 2012;379:1591-1601]

No DSS advantage

Despite the OS advantage, no association was found between NSAID use and improved disease-specific survival (DSS) in both univariate (HR, 0.82; p=0.47) and multivariate analyses (HR, 0.98; p=0.44).

“[These suggest that] 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,” explained the researchers. “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.” [Ann Oncol 2017;28:400-407]

PIK3: Potential biomarker?

NSAID use in patients with PI3K-altered HNSCC treated with surgery reportedly led to a significant DSS and OS advantage. [J Exp Med 2019;216:419-427] “[This suggests] that PIK3CA variations may be a clinically useful marker to identify which patients with HNSCC will benefit from NSAID use,” said the researchers. “[However,] we were unable to test for PI3K. [U]ntil such testing is routine, the [current] data … suggest that giving daily aspirin to patients with [HN cancers] who are receiving CRT may be associated with improved survival.”

Despite the trial’s retrospective nature, the lack of data on duration of and reason for NSAID use, and imbalance in primary tumour sites, the study provides a large cohort of HNSCC patients receiving CRT and concurrent NSAIDs, noted the researchers. More studies are warranted to further elucidate the association between NSAID use and HNSCC.