Aspirin linked to boosted survival in clear cell ovarian cancer

Naveed Saleh, MD, MS, for MDLinx | July 31, 2018

Aspirin utilization was significantly linked to better disease-free and overall survival in women with clear cell ovarian cancer, according to a new study published in Gynecologic Oncology Reports.

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“In this small cohort of women with clear cell ovarian cancer, aspirin use correlated with improved disease free and overall survival, and retained independent significance as a positive prognostic factor,” the authors wrote.

“It is well supported that aspirin, and other non-steroidal anti-inflammatory medications, may have a role in the prevention of malignancy,” wrote the authors, led by Alyssa M. Wield, MD, Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, Cedars-Sinai Medical Center, Los Angeles. “However in recent years, there has been growing interest in incorporating aspirin into the multimodal treatment of various malignancies.”

Unfortunately, women with stage III and IV clear cell ovarian carcinoma respond poorly to standard platinum-taxane chemotherapy, are at increased recurrence risk, and are prone to thromboembolism—all factors that raise morbidity and mortality.

Previous research has shown that aspirin impedes various biologic mechanisms involved in tumor growth such as COX-dependent and COX-independent pathways. In particular, this suppression of COX-dependent pathways decreases inflammation and may slow tumor growth, invasion, and spread. Prior studies have also shown that use of aspirin following diagnosis ameliorates survival in breast, prostate, and colon cancer.

Moreover, amplified mortality reductions have been noted in colorectal cancers harboring PIK3CA mutations when compared with those of wild-type tumor cells. Of note, PIK3CA mutations code for a cell membrane protein kinase that plays a role in tumor growth, differentiation, proliferation, and survival. Tumor cells with PIK3CA have increased activity of the COX-2 pathway and thus release more prostaglandins, which could underlie the enhanced response evident in these cells following aspirin exposure.

PIK3CA mutations also occur in between 20% to 30% of clear cell ovarian cancers, indicating that aspirin use may have a distinct clinical impact on this cancer type. Dr. Wield and colleagues set out to retrospectively identify aspirin users among a cohort of 77 women with clear cell carcinoma at Cedars-Sinai Medical Center (average age of 53 years; 81% white; 17% Asian). The patients were diagnosed between 1995 and 2010, and were administered primary cytoreductive surgery, with the goal of complete surgical resection, followed by at least six rounds of platinum-based chemotherapy. The investigators followed clinical outcomes through 2016.

The team defined aspirin exposure as documentation of either 81 mg or 325 mg aspirin use in two separate medical records spaced more than 6 months apart. Data analysis involved Fisher’s exact test, Kaplan-Meier survival, and Cox regression analysis, with a P < 0.05 deemed significant.

Patient characteristics included:

  • 56% had stage I disease (n=43)
  • 14% had stage II disease (n=11)
  • 25% had stage III disease (n=19)
  • 5% had stage IV disease (n=4)
  • 55% had endometriosis (n=42)
  • 17% were aspirin users (n=13)

All patients had high-grade cancer.

Results showed that aspirin users exhibited significantly longer disease-free survival (HR=0.13; 95% CI=0.13-0.83; P=0.018). Furthermore, after controlling for clear cell ovarian cancer prognostic factors—including age, stage, and cytoreductive status—aspirin use remained a positive prognostic factor (HR=0.13; 95% CI = 0.017-0.947; P=0.044).

Median disease-free survival was not attained in this study. In total, 1 of 13 aspirin users (8%) experienced clear cell ovarian carcinoma recurrence at 24 months vs 18 of 64 aspirin non-users (28%).

“The incidence of post-diagnostic thromboembolism was similar between aspirin users and non-users, indicating that the observed improvement in survival is not likely attributed to prevention or treatment of non-cancer specific causes of death such as deep venous thrombosis and pulmonary embolism,” the researchers wrote.

The team observed no hemorrhagic complications secondary to aspirin use, and aspirin use was safe.

The retrospective design of this study allowed for only correlative—not causative—conclusions. Also, the sample size of the study was small thus limiting statistical power.

“In this small cohort of women with clear cell ovarian cancer, aspirin use correlated with improved disease free and overall survival, and retained independent significance as a positive prognostic factor,” the researchers concluded. “Further research is warranted to confirm these findings before considering aspirin as a therapeutic intervention.”

To read more about this study, click here.  

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