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

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

Medicine

Research output: Contribution to journal › Article › peer-review

48 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 language	English (US)
Pages (from-to)	419-427
Number of pages	9
Journal	Journal of Experimental Medicine
Volume	216
Issue number	2
DOIs	https://doi.org/10.1084/jem.20181936
State	Published - Feb 1 2019

ASJC Scopus subject areas

Immunology and Allergy
Immunology

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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

Hedberg, ML, Peyser, ND, Bauman, JE, Gooding, WE, Li, H, Bhola, NE, Zhu, TR, Zeng, Y, Brand, TM, Kim, MO, Jordan, RCK, VandenBerg, S, Olivas, V, Bivona, TG, Chiosea, SI, Wang, L, Mills, GB, Johnson, JT, Duvvuri, U, Ferris, RL, Ha, P, Johnson, DE & Grandis, JR 2019, 'Use of nonsteroidal anti-inflammatory drugs predicts improved patient survival for PIK3CA-altered head and neck cancer', Journal of Experimental Medicine, vol. 216, no. 2, pp. 419-427. https://doi.org/10.1084/jem.20181936

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title = "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.",

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

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doi = "10.1084/jem.20181936",

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AU - Hedberg, Matthew L.

AU - Peyser, Noah D.

AU - Bauman, Julie E.

AU - Gooding, William E.

AU - Li, Hua

AU - Bhola, Neil E.

AU - Zhu, Tian Ran

AU - Zeng, Yan

AU - Brand, Toni M.

AU - Kim, Mi Ok

AU - Jordan, Richard C.K.

AU - VandenBerg, Scott

AU - Olivas, Victor

AU - Bivona, Trever G.

AU - Chiosea, Simion I.

AU - Wang, Lin

AU - Mills, Gordon B.

AU - Johnson, Jonas T.

AU - Duvvuri, Umamaheswar

AU - Ferris, Robert L.

AU - Ha, Patrick

AU - Johnson, Daniel E.

AU - Grandis, Jennifer R.

PY - 2019/2/1

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N2 - 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.

AB - 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.

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

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