Aspirin/NSAID Use and Improved Survival in Ovarian Cancer

Roxanne Nelson, BSN, RN

July 31, 2018

The use of aspirin or nonsteroidal anti-inflammatory agents (NSAIDs) was associated with improved survival among women with ovarian cancer, according to new findings.

Patients who reported current use of analgesics in the 2 years after a diagnosis of ovarian cancer had improved disease-specific survival with aspirin (hazard ratio [HR], 0.68) and nonaspirin NSAIDs (HR, 0.67) compared with those who never used them.

The study was published online July 17 in the Lancet Oncology.

On the basis of these findings, should women with ovarian cancer now be advised to use aspirin?

That answer is still uncertain, cautions an editorialist writing in an  accompanying commentary.

 "The current data show promise but do not yet give a clear answer, and use of aspirin or other NSAIDs is not without risks," writes Penelope M. Webb, DPhil, QIMR Berghofer Medical Research Institute, Brisbane, Australia. "Additionally, if these medications do improve survival, further research is needed to understand the mechanisms of this effect."

Study Details

The study was led by Melissa A. Merritt, PhD, from the University of Hawaii Cancer Center in Honolulu.

The team evaluated data from two ongoing long-term trials conducted in US nurses: the Nurses' Health Study (NHS) with 121,700 participants, which began in 1976, and the Nurses' Health Study II (NHSII) involving 116,429 participants, which began in 1989.

Participants who were eligible for the final analysis had confirmed invasive, stage I to III epithelial ovarian cancer, and data available on analgesic use.  A total of 1143 (907 from NHS; 236 from NHSII) cases of ovarian cancer were included in the analyses. The premedication analysis included 1031 women, and the analyses of postdiagnosis use included 964 women.

The primary objective was to determine whether regular use of aspirin (≥2 days per week), NSAIDs, or paracetamol before and after a diagnosis of ovarian cancer was associated with cancer-specific survival.

Improvement with Postdiagnosis Use Only

The authors did not find an association between aspirin use before diagnosis and survival; conversely, however, women using aspirin after their diagnosis had improved survival. This was particularly significant for those taking one to five tablets per week (HR, 0.69) and 2 to 5 days per week (HR, 0.59) (current users, P for trend = .72).

There were also no associations between cancer-specific survival and prediagnosis nonaspirin NSAID use or paracetamol used before or after diagnosis.

For users of nonaspirin NSAIDs after their diagnosis, ovarian cancer–specific survival improved compared with that in never-users (HR, 0.67). As with aspirin, it was significant for use of one to five tablets per week (HR, 0.62) and 2 to 5 days per week (HR, 0.63).

The authors also conducted an analysis of changes in analgesic use from prediagnosis to postdiagnosis. They found that women who began using aspirin regularly (HR, 0.44) or nonaspirin NSAIDs (HR, 0.46) after diagnosis also had a lower risk for ovarian cancer–specific death than did never users.

Definitive Answers From Randomized Trials

In her editorial, Webb notes that a striking finding from this study and others is the "magnitude of the suggested benefit associated with regular postdiagnosis use of aspirin or other NSAIDs."

"Similarly striking is the potentially greater survival benefit, also reported in other cancer types, for women who started using aspirin or NSAIDs after their cancer diagnosis compared to those who used them before diagnosis and continued afterwards," she writes.

Webb points out that the authors conducted extensive sensitivity analyses to minimize the possibility of confounding by indication, although it could not be ruled out entirely. For example, patients who had a poor response to treatment or an early recurrence might have been less likely to continue or initiate the use of aspirin or NSAIDs and were more likely to die of their disease. In this regard, she says, "the biennial data collection in the Nurses' Health Studies is a strength because the investigators had longitudinal data about medication use, but also introduces complexity because women reported use at varying points in relation to their disease and treatment trajectory."

Further research is needed to understand the underlying mechanism, such as whether the observed benefit will vary with dose or timing (during vs after chemotherapy), Webb comments. But definitive answers might come only from randomized trials, she adds.

"In the meantime, further prospective observational studies that can provide reassurance regarding the comparability of analgesic users and non-users might resolve some of the uncertainty," Webb concludes.

The study was supported in part by the National Institutes of Health, the Marsha Rivkin Center for Ovarian Cancer Research, and Skacel Family Scholar Award. The authors and editorialist have disclosed no relevant financial relationships.

Lancet Oncol. Published online July 17, 2018. Abstract, Editorial

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