Aspirin Associated With Better CRC Survival in Tumors With Low CD274

Aspirin had a greater effect on colorectal cancer survival in patients with low-level CD274 (PD-L1) expression compared with tumors with high-level CD274 expression, according to the results of a study published in the Journal of Clinical Oncology.

Previous research had shown that aspirin and immune checkpoint blockade may have a synergistic effect of the activation of T cell-mediated antitumor immune response. In this study, Tsuyoshi Hamada, MD, PhD, of Dana-Farber Cancer Institute and Harvard Medical School in Boston, and colleagues tested their hypothesis that the beneficial effects of aspirin in patients with colorectal cancer may be greater in tumors with lower CD274 expression.

“Our data suggest that overexpression of the CD274 immune checkpoint ligand may attenuate survival benefits associated with aspirin use and that tumor CD274 expression status may serve as a biomarker to select patients for adjuvant aspirin therapy,” Hamada and colleagues wrote. “Given growing popularity of immune checkpoint inhibitors for cancer treatment, our findings, if validated, may have considerable clinical implications for adjuvant aspirin use in the era of immunotherapy.”

The study included data from 617 patients with rectal and colon cancer taken from the Nurses’ Health Study and the Health Professionals Follow-Up Study. The researchers looked at post-diagnosis aspirin use and examined its association with patient survival in strata of tumor CD274 expression status measured using immunohistochemistry.

During a median of 11.5 years of follow-up there were 325 all-cause deaths and 118 cancer-specific deaths. Post-diagnosis aspirin use was associated with longer colorectal cancer–specific survival in patients with low-level tumor CD274 expression (P < .001), but the same was not true in patients with high-level expression. The hazard ratio for regular aspirin users was 0.16 (95% CI, 0.06–0.41) in patients with low CD274 and was 1.01 (95% CI, 0.61–1.67) in patients with high CD274.

“Our findings supporting the differential effects of aspirin according to immune checkpoint status underscore the potential of dual prostaglandin inhibition and immune checkpoint blockade as a combination immunotherapy strategy to further improve clinical outcome,” the researchers wrote.

The researchers found a significant interaction between post-diagnosis aspirin use and tumor CD274 expression status in both the colorectal cancer–specific survival analysis and the overall survival analysis. In addition, the prognostic association of aspirin use by CD274 status was consistent in patients with microsatellite stable tumors or PIK3CA wild-type disease, as well as in strata of cyclooxygenase-2 expression, CDX2 expression, tumor-infiltrating lymphocytes, or pre-diagnosis aspirin use status.

Hamada and colleagues acknowledged several limitations to their study including a lack of data on cancer treatment, which could be an important variable. In addition, there was limited information on cancer recurrence.

“Importantly, our patients with colorectal cancer were derived from a large number of hospitals throughout the United States (rather than a few hospitals), which increases the generalizability of our findings,” they wrote.