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Use of NSAIDs improves survival in head and neck cancer subset
Regular use of NSAIDs significantly improved OS and disease-specific survival among patients with PIK3CA-altered head and neck squamous cell carcinoma, according to results of a prospective study published in Journal of Experimental Medicine.
“Our results suggest that the use of NSAIDs could significantly improve outcomes for not only patients [with head and neck cancer], but also patients with other cancers that contained the PIK3CA mutation,” Jennifer R. Grandis, MD, professor of otolaryngology, head and neck surgery, and member of the Helen Diller Family Comprehensive Cancer Center at University of California, San Francisco, said in a press release. “The magnitude of the apparent advantage is strong and could potentially have a positive impact on human health.”
Previous studies have shown an association between regular aspirin use and improved OS in patients with colorectal cancer carrying a mutated PIK3CA gene.
In this study, researchers examined the impact of NSAID use on survival among 266 patients (median age, 60 years; 73% men) with HNSCC who underwent treatment with curative-intent surgery and adjuvant therapy that included radiation and chemotherapy.
Among the patients, 37 (14%) had PIK3CA mutation, 29 (11%) had amplification of the gene, and nine (3%) had both mutation and amplification.
Researchers defined regular NSAID use as two or more doses per week for 6 months or more. Regular users included 74 patients without PIK3CA alterations and 25 patients with PIK3CA alterations.
Most regular NSAID users (93%) reported aspirin as part of their regimen, and 73% took aspirin exclusively. Three-quarters of aspirin-exclusive users took daily, low-dose (81 mg) versions of the drug.
Most regular users (86%) started taking NSAIDs after they were diagnosed with HNSCC.
Results showed that among patients with PIK3CA mutations or amplification, regular use of NSAIDs significantly increased disease-specific survival (HR = 0.23; 95% CI, 0.09-0.62) and OS (HR = 0.31; 95% 0.14-0.69) compared with nonregular use.
For these patients, researchers reported predicted 5-year disease-specific survival of 72% for regular NSAID users and 25% for nonregular users, and predicted 5-year OS of 78% for regular users vs. 45% for nonregular users, with median disease.
Researchers observed no improvement in survival outcomes with NSAID use among patients with nonPIK3CA-altered HNSCC.
Researchers further studied the theory behind NSAIDs and improved survival in mice with tumors containing a mutant PIK3CA gene. The findings indicated that the mutation or amplification activates PI3K pathway signals, likely resulting in elevated PGE2 secretion through activation of the COX2 enzyme and leading to enhanced NSAID sensitivity.
Study limitations included the lack of randomization and inconsistencies in the type, timing and dosing of NSAIDs.
“NSAID use likely confers a statistically and clinically significant advantage in OS in PIK3CA-alrtered head and neck cancer through direct interaction between PI3K and COX pathways,” Grandis said. “Given the marked mortality of this disease, the researchers have designed a prospective, randomized clinical trial to address the initial study’s limitations and assess the clinical significance of this therapeutic use.” – by John DeRosier
Disclosures: Grandis reports no relevant financial disclosures. Please see the study for all other authors’ relevant financial disclosures.