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

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.

Source: The Journal of Experimental Medicine - February 4, 2019 Category: Internal Medicine Authors: 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., Duvvur Tags: Solid Tumors Articles Source Type: research