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NSAID benefit in colon cancer supported in study

June 17, 2017

Regular use of aspirin or other nonsteroidal anti-inflammatory drugs (NSAIDs) had a significant association with improved survival among long-term survivors of colorectal cancer, a retrospective review of registry data showed.

Overall, NSAID users had a 24% reduction in the survival hazard. However, separate analyses by type of NSAID showed that the benefit was limited to aspirin use, and patients who used other NSAIDs or aspirin plus NSAIDs did not have a survival benefit. Cause-specific survival (CSS) improved by 56% among aspirin users.

Further analysis showed that the overall survival (OS) benefit associated with NSAID use was driven by the subgroup of patients with KRAS wild-type tumors, Polly A. Newcomb, PhD, of Fred Hutchinson Cancer Research Center in Seattle, and co-authors reported online in the Journal of Clinical Oncology.

“Patients who initiated aspirin use after diagnosis had improved OS, whereas both initiated and continued use seemed to be associated with more favorable CSS. Although both observational and randomized studies provided convincing evidence of aspirin as an effective chemopreventive agent for colorectal cancer, aspirin is not generally recommended for primary prevention of colorectal cancer for people at average risk of cardiovascular disease because of the potential risks.

“Aspirin for secondary prevention of colorectal cancer, particularly in subgroups such as those with KRAS wild-type tumors, is supported by our study,” the researchers continued. “Future studies are needed to find the best timing, dose, and duration of aspirin use to identify subgroups of patients with colorectal cancer for whom the benefits of aspirin outweigh its risks.”

Multiple studies demonstrated a significant association between long-term regular use of NSAIDs and a reduced risk of colorectal neoplasia. Limited information existed about the potential benefits of prediagnostic or postdiagnostic NSAID use for colorectal cancer survival. Moreover, studies to date yielded inconsistent data about the effect of NSAID use on colorectal cancer survival, Newcomb and co-authors noted in their introduction.

To examine more closely the association between postdiagnostic use of NSAIDs and colorectal cancer survival, the investigators analyzed data from the Colon Cancer Family Registry, an international consortium comprising data for 32,000 survivors of colorectal cancer, their relatives, and control groups. The analysis focused on 2,419 patients who had new diagnoses of colorectal cancer during 1997 to 2008 and who were followed for approximately 10 years.

The team performed a series of tumor marker tests, using DNA extracted from paraffin-embedded, formalin-fixed tumor specimens. The specimens were evaluated for microsatellite instability status, protein expression for multiple genes (including BRAFV600 and KRAS), and methylation phenotype.

NSAID use (including aspirin) was determined by means of interviews at baseline and follow-up. For each patient, the authors determined the approximate date of initiation of NSAIDs, the type of NSAID used, and the duration of use. The findings for NSAID use were compared with subsequent survival.

The study population included 1,397 NSAID non-users and 1,022 who used NSAIDs at some point after diagnosis of colorectal cancer. Initial patient interviews occurred a median duration of 5.9 years after colorectal cancer diagnosis, and 381 patients died during a median follow-up of 4.9 years from the baseline interview.

The data showed a statistically significant favorable association between postdiagnostic NSAID use and OS (HR 0.76, 95% CI 0.62-0.94). The association was similar for patients who used aspirin, non-aspirin NSAIDs, or a combination of aspirin and other NSAIDs. For the analysis of CSS, the association remained significant only for regular users of aspirin (HR 0.44, 95% C 0.25-0.77).

KRAS status was known for approximately two-thirds of the patients and was wild type in 1,244 of the specimens. Comparison of KRAS status and NSAID use showed that 548 NSAID users had KRAS wild-type tumors, and 230 had KRAS-mutant tumors. The authors found that only those patients with KRAS wild-type tumors derived a survival benefit from postdiagnostic NSAID use (HR 0.64, 95% CI 0.48-0.85, P=0.02 for interaction). Patients with KRAS-mutant tumors had a nonsignificant 20% increase in the survival hazard in association with NSAID use.

The interaction between NSAID use and KRAS status did not extend to CSS, although a trend toward a favorable effect was observed (P=0.08).

Longer duration of NSAID use (any NSAID and aspirin only) also had a significant, favorable effect on both OS and CSS (P<0.05 for trend). An exploratory analysis showed that the association between duration of NSAID use and OS remained significant only for patients with KRAS wild-type tumors. Finally, the authors found that patients who initiated NSAID use after colorectal cancer diagnosis had significantly better OS (HR 0.71, 95% CI 0.54-0.92), but not patients who reported NSAID use before and after diagnosis or patients who discontinued NSAID use.

Newcomb disclosed no relevant relationships with industry. Some of her coauthors disclosed relationships with CVS Health, Gilead Sciences, Boston Biomedical, Ambry Genetics, and Cancer Prevention Pharmaceuticals, as well as having material patent interests.

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