No mRCC survival benefit seen with NSAID use

While they may have potential anti-tumor effects in other cancers, non-steroidal anti-inflammatory drugs (NSAIDs) do not appear to confer a survival benefit in metastatic renal cell carcinoma (RCC), results of a large, recently published meta-analysis suggest.

For patients with metastatic RCC patients who were taking aspirin, there were no differences in overall or progression-free survival (PFS) versus non-NSAID users, according to results of a study published in Kidney Cancer (2018; 2:27-46).

By contrast, overall survival was significantly worse for non-aspirin NSAID users versus non-NSAID users, according to investigator Lana Hamieh, MD, and colleagues at Dana-Farber Cancer Institute, Boston; the University of California, San Diego; and Pfizer, Inc.

Those results corroborate earlier studies showing worse outcomes associated with NSAID use in localized kidney cancer, which contrast with the potentially beneficial effects of NSAIDs seen in other cancers, said Ketan K. Badani, MD, of Icahn School of Medicine at Mount Sinai, New York, who was not involved with the study.

“This dichotomy points to the unique tumor biology of renal cell carcinoma,” Dr. Badani told Urology Times.

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Although this is the largest study to date assessing the use of NSAIDS in metastatic RCC, Dr. Badani added, it is important to note that the data set is retrospective and not designed to specifically to address the impact of NSAIDs on survival. Of note, data on dose, duration, and frequency of NSAID use were not available.

“This study found an association between NSAIDS and poor outcome, but not a causation for overall survival,” Dr. Badani said. “However, this does lay the groundwork for a prospective study to answer this important question.”

The pooled, retrospective analysis included 4,736 patients with metastatic RCC who had been enrolled in Pfizer-sponsored phase II and III clinical trials of VEGF targeted therapy, mTOR targeted therapy, or interferon alpha. Of those patients, 649 (13%) were non-aspirin NSAID users, 457 (10%) were aspirin users, and 61 (1%) used both.

Next:Overall survival significantly worse for users of non-aspirin NSAIDsOverall survival, the primary endpoint of the study, was significantly worse for users of non-aspirin NSAIDs as compared to NSAID non-users (hazard ratio, 1.47; 95% CI, 1.31-1.65; p <.0001). The median overall survival was 11.6 versus 21.1 months for those groups, respectively.

Likewise, PFS was significantly worse for non-aspirin NSAID users versus NSAID non-users (hazard ratio, 1.29; 95% CI, 1.16-1.44; p <.0001), investigators reported.

For aspirin users, there was no significant difference versus NSAID non-users in either overall survival (hazard ratio, 1.0; 95% CI, 0.86-1.18; p=.9567) or PFS (hazard ratio, 1.07; 95% CI, 0.93-1.22; p=.3515), according to data from the study.

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These findings contrast with what has been seen in colorectal cancer, where there is increasing interest in the role of NSAIDs as anti-tumor agents, investigators said. Clinical trials have suggested a modest benefit of NSAIDs in preventing colorectal adenoma recurrence.

There have been limited studies to date on the impact of NSAIDs in RCC, but only in patients with localized, rather than metastatic disease, according to investigators.

In one previous meta-analysis of 20 observational studies, use of non-aspirin NSAIDs was associated with a higher incidence of RCC, they said (Int J Cancer 2014; 134:384-96).

Similarly, an analysis of the Nurses’ Health Study and the Health Professionals Follow-up study showed an increased risk of RCC with longer use of non-aspirin NSAIDs, but not for aspirin (Arch Intern Med 2011; 171:1487-93).

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