NSAID Use Associated With Shorter PFS, OS in Metastatic RCC

May 7, 2018

A pooled retrospective analysis of nearly 5,000 mRCC patients in phase II and III trials showed PFS among NSAIDs users was half that of NSAIDs nonusers.

Ibuprofen, aspirin, and other non-steroidal anti-inflammatory drugs (NSAIDs) have demonstrated promising anticancer properties in a number of tumor types. However, NSAID use appears to be associated with shorter overall survival (OS) in patients with metastatic renal cell carcinoma (mRCC), according to a new study published by Lana Hamieh, MD, and colleagues in Kidney Cancer.

Few studies have evaluated the effect of NSAIDs on patients with localized RCC, and none have had characterized outcomes for patients with mRCC, according to Hamieh et al. They conducted a pooled retrospective analysis of 4,736 mRCC patients treated in phase II and III clinical trials. Patients were categorized as users of aspirin (ASA) only, non-ASA NSAIDs, and ASA and non-ASA NSAIDs; and as NSAIDs nonusers. The primary endpoint was OS, and secondary endpoints were progression free survival (PFS), overall response rate (ORR), and adverse events (AEs).

The analysis showed that 457 patients (10%) were ASA-only users, 639 patients (13%), were non-ASA NSAIDs only users, 61 patients (1%) were ASA and non-ASA NSAIDS users, and 3,579 (76%) were NSAIDs non-users. OS and PFS were significantly worse in non-ASA NSAIDs users compared with NSAIDs nonusers (OS, hazard ratio [HR], 1.47). The median PFS was 11.6 months vs 21.1 months, respectively (HR, 1.29). The study showed that were no significant differences in survival when comparing NSAIDs nonusers with ASA users or ASA and non-ASA NSAIDs users.

The current study is the largest to date investigating the impact of NSAIDs on mRCC, according to lead study investigator Rana R. McKay, MD, from the University of California San Diego’s Moores Cancer Center, La Jolla, California.  However, she emphasized that these findings should be interpreted with caution. McKay said the findings should be viewed as hypothesis-generating rather than definitive. She noted that the analysis was limited by its retrospective nature, and pointed out that the four groups studied were not balanced in terms of baseline characteristics and disease characteristics.

Dr. McKay said there is an urgent need to better understand NSAID mechanisms of action. The antitumorigenic mechanism of NSAIDs has been attributed largely to their cyclooxygenase (COX) inhibitory activity, which leads to suppression of prostaglandin synthesis and ultimately decreases inflammation. In RCC, COX-2 expression is present in the majority of the tumors and correlates with poorer survival and other negative factors.

Association of the use of non-ASA NSAIDs with reduced survival was consistent when looking at untreated or previously treated patients, and also when looking at the type of targeted therapy received, either vascular endothelial growth factor (VEGF) or mammalian target of rapamycin (mTOR) targeted therapy. The researchers write that additional studies are warranted to investigate the impact of NSAID use on outcomes from treatment with new agents such as cabozantinib and nivolumab.