Non-Aspirin NSAID Use Associated With Shorter Survival in Metastatic RCC

Metastatic renal cell carcinoma (mRCC) patients who use non-aspirin NSAIDs have  poorer overall survival than aspirin users and nonsteroidal anti-inflammatory drugs (NSAID) non-users, according to a new pooled retrospective analysis presented at the 15^th International Kidney Cancer Symposium, held November 4–5 in Miami.

“NSAIDs are among the most commonly utilized drugs internationally,” said Rana McKay, MD, of the Dana-Farber Cancer Institute in Boston. Increasingly, studies suggest that aspirin and other NSAIDs can decrease both the incidence of cancer and death from cancer, but their role in RCC-and in particular in metastatic disease-has not been thoroughly studied.

The new study was a pooled analysis of 4,736 patients with mRCC treated in Pfizer-sponsored phase II and III trials between 2003 and 2011. The patients were grouped into four cohorts: aspirin users (457 patients); non-aspirin NSAID users (639 patients); aspirin plus non-aspirin NSAID users (61 patients); and users of neither aspirin nor other NSAIDs (3,579 patients).

There were some differences between these groups at baseline. Aspirin users tended to be older than users of other NSAIDs or non-users, and aspirin use was higher in the United States than elsewhere in the world. Bone and liver metastases were more common among non-aspirin NSAID users, and IMDC poor-risk patients were more likely to be non-aspirin NSAID users or combined aspirin and other NSAID users than non-users or aspirin-alone users.

The median overall survival for non-users was 21.1 months, which served as the reference group. Aspirin users had a median overall survival of 23.6 months, which was similar (hazard ratio [HR], 1.00; 95% CI, 0.86–1.18; P = .9567). Users of aspirin along with other NSAIDs had a median overall survival of 15.2 months (HR, 1.43; 95% CI, 0.99–2.06; P = .0515). Non-aspirin NSAID users fared the worst, with a median overall survival of 11.6 months (HR, 1.47; 95% CI, 1.31–1.65; P < .0001). “We did conduct multivariable analyses and our results were positive even after that adjustment,” McKay said.

The poorer overall survival with non-aspirin NSAIDs held in patients undergoing first-line and second-line therapy, and in patients receiving VEGF targeted therapy and mTOR targeted therapy. That group also had worse objective response rates, at 16% compared with 25% for the full cohort, 28% for aspirin-only patients, 20% for the combination of NSAIDs, and 26% in those not using any NSAID.

“Our study is the largest to date evaluating the impact of NSAIDs on outcomes in patients with mRCC,” McKay said. She added that further observational studies are warranted to validate the findings, and preclinical studies are also needed to elucidate the mechanism that may lead to poorer outcomes with non-aspirin NSAIDs.