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

• Published in: The Journal of experimental medicine Vol. 216; no. 2; pp. 419 - 427
• Main Authors: Hedberg, Matthew L., Peyser, Noah D., Bauman, Julie E., Gooding, William E., Li, Hua, Bhola, Neil E., Zhu, Tian Ran, Zeng, Yan, Brand, Toni M., Kim, Mi-Ok, Jordan, Richard C.K., VandenBerg, Scott, Olivas, Victor, Bivona, Trever G., Chiosea, Simion I., Wang, Lin, Mills, Gordon B., Johnson, Jonas T., Duvvuri, Umamaheswar, Ferris, Robert L., Ha, Patrick, Johnson, Daniel E., Grandis, Jennifer R.
• Format: Journal Article
• Language: English
• Published: United States Rockefeller University Press 04.02.2019
• Subjects: Adult; Aged; Animals; Anti-Inflammatory Agents, Non-Steroidal - administration & dosage; Carcinoma, Squamous Cell - enzymology; Carcinoma, Squamous Cell - genetics; Carcinoma, Squamous Cell - mortality; Carcinoma, Squamous Cell - therapy; Class I Phosphatidylinositol 3-Kinases - genetics; Class I Phosphatidylinositol 3-Kinases - metabolism; Disease-Free Survival; Female; Head and Neck Neoplasms - enzymology; Head and Neck Neoplasms - genetics; Head and Neck Neoplasms - mortality; Head and Neck Neoplasms - therapy; Humans; Male; Mice; Mice, Inbred NOD; Middle Aged; Mutation; Neoplasm Proteins - genetics; Neoplasm Proteins - metabolism; Survival Rate; Xenograft Model Antitumor Assays
• ISSN: 0022-1007; 1540-9538; 1540-9538
• DOI: 10.1084/jem.20181936

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.