Use of nonsteroidal anti-inflammatory drugs predicts improved patient survival for PIK3CA-altered head and neck cancer

Abstract

PIK3CA is the most commonly altered oncogene in head and neck squamous cell carcinoma (HNSCC). We evaluated the impact of nonsteroidal anti-inflammatory drugs (NSAIDs) on survival in a PIK3CA-characterized cohort of 266 HNSCC patients and explored the mechanism in relevant preclinical models including patient-derived xenografts. Among subjects with PIK3CA mutations or amplification, regular NSAID use (≥6 mo) conferred markedly prolonged disease-specific survival (DSS; hazard ratio 0.23, P = 0.0032, 95% CI 0.09–0.62) and overall survival (OS; hazard ratio 0.31, P = 0.0043, 95% CI 0.14–0.69) compared with nonregular NSAID users. For PIK3CA-altered HNSCC, predicted 5-yr DSS was 72% for NSAID users and 25% for nonusers; predicted 5-yr OS was 78% for regular NSAID users and 45% for nonregular users. PIK3CA mutation predicted sensitivity to NSAIDs in preclinical models in association with increased systemic PGE2 production. These findings uncover a biologically plausible rationale to implement NSAID therapy in PIK3CA-altered HNSCC.

Safety and efficacy of photobiomodulation therapy in oncology: A systematic review

“…For example, 35% expressing dysregulation in the PI3K pathway, a putative site of action of PBM in OSCC. 100 Animal and clinical trials allow assessment of the effect of PBM on the tumor and the tumor microenvironment (e.g. immune function, the surface microenvironment, and epithelial and connective tissue interactions).…”

PIK3CA Gene Mutations in Solid Malignancies: Association with Clinicopathological Parameters and Prognosis

“…However, differential response of PIK3CA-mutated vs. WT tumors, to PI3K-targeted therapies, remains controversial in HNSCC. While one study revealed no association between PIK3CA and responsiveness to PI3K-targeted drugs [94], another group reported PIK3CA mutations to be associated with potential benefit from matched targeted therapy in parathyroid carcinoma [95]. In a recent study evaluating the effect of nonsteroidal anti-inflammatory drugs (NSAID) on survival in head and neck cancer, patients with PIK3CA mutations or amplification showed prolonged disease-specific survival and overall survival with NSAID use as compared with non-NSAID users [96].…”

Association of Nonsteroidal Anti-inflammatory Drug Use With Survival in Patients With Squamous Cell Carcinoma of the Head and Neck Treated With Chemoradiation Therapy

“…[7][8][9][10][11] Recently, however, Hedberg et al found that regular NSAID use at any time improves disease-specific survival (DSS) and overall survival (OS) in patients with PI3K-altered HNSCC. 12 Less explored is the association of NSAID use with definitive chemoradiation therapy (CRT). This cohort study was performed using a large single institution HNSCC database to further examine the survival outcomes associated with NSAID use during CRT.…”