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. Ferris; Patrick Ha; Daniel E. Johnson; Jennifer R. Grandis

doi:10.1084/jem.20181936

DOI: 10.1084/jem.20181936 | Published January 25, 2019

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.

Submitted: 11 October 2018
Revision received 30 November 2018
Accepted: 20 December 2018

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© 2019 Hedberg et al. http://www.rupress.org/terms/https://creativecommons.org/licenses/by-nc-sa/4.0/This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms/). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 International license, as described at https://creativecommons.org/licenses/by-nc-sa/4.0/).