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

Matthew L. Hedberg, Noah D. Peyser, Julie E. Bauman, William E. Gooding, Hua Li, Neil E. Bhola, Tian Ran Zhu, Yan Zeng, Toni M. Brand, Mi Ok Kim, Richard C.K. Jordan, Scott VandenBerg, Victor Olivas, Trever G. Bivona, Simion I. Chiosea, Lin Wang, Gordon B. Mills, Jonas T. Johnson, Umamaheswar Duvvuri, Robert L. FerrisPatrick Ha, Daniel E. Johnson, Jennifer R. Grandis

    Research output: Contribution to journalArticle

    15 Scopus citations

    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.

    Original languageEnglish (US)
    Pages (from-to)419-427
    Number of pages9
    JournalJournal of Experimental Medicine
    Volume216
    Issue number2
    DOIs
    StatePublished - Feb 1 2019

    ASJC Scopus subject areas

    • Immunology and Allergy
    • Immunology

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  • Cite this

    Hedberg, M. L., Peyser, N. D., Bauman, J. E., Gooding, W. E., Li, H., Bhola, N. E., Zhu, T. R., Zeng, Y., Brand, T. M., Kim, M. O., Jordan, R. C. K., VandenBerg, S., Olivas, V., Bivona, T. G., Chiosea, S. I., Wang, L., Mills, G. B., Johnson, J. T., Duvvuri, U., ... Grandis, J. R. (2019). Use of nonsteroidal anti-inflammatory drugs predicts improved patient survival for PIK3CA-altered head and neck cancer. Journal of Experimental Medicine, 216(2), 419-427. https://doi.org/10.1084/jem.20181936