NSAIDs: No survival benefit in renal cell carcinoma

Nonsteroidal anti-inflammatory drugs (NSAIDs) don’t boost survival in patients with metastatic renal cancer (mRCC), according to a new study published in Kidney Cancer.

“Recently, there has been increasing interest in the role of NSAIDs as anti-tumorigenic drugs, particularly in colorectal cancer (CRC),” wrote the authors, led by Lana Hamieh, MD, and Raphael B. Moreira, MD, both of Dana-Farber Cancer Institute, Boston, MA. “Epidemiological data demonstrate that NSAID use, including long-term [aspirin] use, decreases incidence, metastasis, and mortality risk in several cancers.”

During this epoch of drug repurposing, NSAIDs have been widely examined for their anti-cancer effects. Experts hypothesize that NSAIDs exercise antitumor activity by inhibiting cycolooxygenase-2 (COX-2), as well as other potential mechanisms. In rat models of colorectal cancer, NSAIDs suppressed formation of malignant lesions and regressed tumors. Furthermore, limited clinical evidence suggests that NSAIDs modestly prevent the recurrence of colorectal adenomas.

Few researchers have examined the role of aspirin (ASA) and non-ASA NSAIDs in renal cell carcinoma, and no studies have evaluated the effects of these drugs on mRCC—despite it being important in the evolving milieu of metastatic care.

“[NSAIDs] inhibit tumor growth by inducing apoptosis of tumor cells and inhibiting the Wnt/β-catenin signaling pathway,” the researchers wrote. “In RCC, COX-2 expression is present in the majority of the tumors and correlates with worse stage, grade, and microvessel density, and poorer survival.”

For this study, the team examined the effect of ASA and non-ASA NSAIDs on overall survival (OS), progression free survival (PFS), and objective response rate (ORR) using a large clinical trials database of patients with mRCC treated with targeted therapies.

A pooled retrospective analysis of 4,736 mRCC patients treated in phase 2 and phase 3 clinical trials was conducted. The researchers identified four groups of patients: ASA only users (n=457), non-ASA NSAID only users (n=639), ASA and non-ASA NSAID users (n=61), and NSAID non-users (n=3,579).

Most patients in the study were less than 65 years old (69%), men (71%), and with good performance status (98%). In addition, most patients had a history of nephrectomy (70%) and had no history of systemic therapy (67%).

The primary endpoint was OS, which the team defined as “the time from randomization for randomized studies or from initiation of therapy for non-randomized studies to death from any cause.” Secondary endpoints included PFS, ORR, and adverse events.

The researchers found median survival times in non-ASA NSAID users were shorter when compared with NSAID non-users (11.6 vs 21.1 months for OS and 4.6 vs 7.4 months in PFS). They found no difference in survival in ASA users or ASA and non-ASA NSAID users compared with NSAID non-users.

The authors suggested that that one reason that NSAIDs didn’t boost survival in this study was because they were not taken at high enough doses; lower doses of NSAIDs are needed for pain management when compared with tumor growth inhibition.

One limitation is that the database was not designed for this study, and “duration, dosage or constituents of the drugs used were not captured.”

Specifically, indications, dosages, and durations of drug use lay at the discretion of treating physicians. Furthermore, many of the patients in this study were treated outside of the United States where population characteristics could differ.

“Our data are thought provoking and warrant validation,” the researchers concluded. “Pre-clinical studies investigating the interaction of NSAIDS with targeted therapy and immunotherapy in RCC are warranted to corroborate our results and highlight the mechanism of action underlying our observations.”

This study was funded by Pfizer.

To read more about this study, click here.