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

J Exp Med. 2019 Feb 4;216(2):419-427. doi: 10.1084/jem.20181936. Epub 2019 Jan 25.

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.

Publication types

  • Clinical Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • 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

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Neoplasm Proteins
  • Class I Phosphatidylinositol 3-Kinases
  • PIK3CA protein, human