Improved head and neck cancer survival with NSAIDs

By Will Boggs MD

NEW YORK (Reuters Health) - 29/1/2019

The use of nonsteroidal anti-inflammatory drugs (NSAIDs) is associated with improved survival in patients with PIK3CA-altered head and neck cancer, researchers report.

"We were surprised that there was such a strong association between a primary head and neck cancer containing a mutation or amplification of the PIK3CA oncogene, regular use of NSAIDs after head and neck cancer treatment, and markedly prolonged patient survival," Dr. Jennifer R. Grandis from University of California, San Francisco, told Reuters Health by email.

Regular aspirin use has been found to protect against development of head and neck squamous cell carcinoma (HNSCC), but studies investigating the potential survival benefits of NSAIDs have yielded inconsistent findings.

Activating mutations in PIK3CA, which induces production of prostaglandin E2 via cyclooxygenase-2 enzyme, a target of NSAIDs, are common in HNSCC. Some studies have reported a correlation between regular NSAID use and improved survival in patients with other carcinomas harboring such mutations.

Dr. Grandis's team investigated whether regular NSAID use is associated with improved disease-specific survival and overall survival (OS) in patients with PIK3CA-mutated or -amplified HNSCC.

Among the 266 patients in the study, 75 (28%) harbored mutations and/or amplification of PIK3CA. There was no association between NSAID use and PIK3CA status, according to the January 25th Journal of Experimental Medicine online report.

Disease-specific survival among patients with wild-type PIK3CA was unaffected by regular NSAID use, but regular NSAID use was strongly associated with improved disease-specific survival for patients with mutated and/or amplified PIK3CA (72% at 5 years in regular users versus 25% in nonregular users).

Similarly, OS among patients with unaltered PIK3CA did not differ between regular and nonregular NSAID users, whereas among patients with altered PIK3CA, 5-year OS was significantly greater for regular NSAID users (78%) than for nonregular NSAID users (45%).

For patients taking regular NSAIDs, PIK3CA alteration predicted significantly improved survival probability in both HPV-positive and HPV-negative disease, whereas PIK3CA alteration was associated with worse survival probability irrespective of HPV status for nonregular NSAID users.

In mouse models of HNSCC, the NSAIDs sulindac, celecoxib, and aspirin reduced the growth rates of mutated PIK3CA tumors but not of wild-type PIK3CA tumors.

"If these findings are validated in a prospective clinical trial (which we have designed and hope to implement in 2019), routine testing of head and neck cancers for the presence of a genetic alteration that activates the PI3K signaling pathway could guide the use of NSAIDs and have a significant impact on clinical outcome for a significant subset of cancer patients," Dr. Grandis said.

"While I believe that these findings could change medical practice, it is important to verify the results in a prospective study, since NSAIDs have side effects, such as bleeding, and are unlikely to be beneficial in unselected patient populations," she said.

SOURCE: J Exp Med 2019.

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