Tumor CD274 (PD-L1) Expression and Survival With Aspirin Use in Colorectal Cancer


Key Points

  • Postdiagnosis aspirin use was associated with improved cancer-specific survival vs nonuse among patients with colorectal cancer who have low, but not high, tumor CD274 expression.
  • A similar relationship was observed for overall survival.

According to a study reported by Hamada et al in the Journal of Clinical Oncology, postdiagnosis aspirin use was associated with improved survival vs nonuse among patients with colorectal cancer who have lower, but not higher, tumor levels of CD274 (programmed cell death 1 ligand 1; PD-L1).

Study Details

The study examined the association of postdiagnosis aspirin use with survival according to tumor CD274 expression measured by immunohistochemistry using data from 617 patients with rectal and colon cancer in the Nurses’ Health Study and the Health Professionals Follow-up Study. Disease stage was I in 25% of patients, II in 34% patients, III in 29%, and IV in 7%. Low CD274 tumor expression was found in 127 nonusers of aspirin and 106 regular users postdiagnosis, and high CD274 expression was found in 221 and 163, respectively. Median follow-up was 11.5 years. Multivariable Cox proportional hazards regression models controlled for potential confounders, including disease stage; microsatellite instability status; CpG island methylator phenotype; long interspersed nucleotide element-1 methylation; cyclooxygenase-2 and CDX2 expression; and KRAS, BRAF, and PIK3CA mutation status.

Outcomes With Aspirin Use by CD274 Expression

Significant interactions were observed between postdiagnosis aspirin use and tumor CD274 expression status in colorectal cancer–specific survival (P < .001 for interaction) and in overall survival (P = .004 for interaction). The adjusted hazard ratios for cancer-specific mortality were 0.16 (95% confidence interval [CI] = 0.06–0.41) for aspirin users vs nonusers with low CD274 expression and 1.01 (95% CI = 0.61–1.67) for aspirin users vs nonusers with high expression. The adjusted hazard ratios for all-cause mortality were 0.38 (95% CI = 0.23–0.65) for aspirin users vs nonusers with low CD274 expression and 0.98 (95% CI = 0.62–1.55) for aspirin users vs nonusers with high expression.

The interaction of postdiagnosis aspirin use and CD274 expression status for cancer-specific survival appeared to be consistent across subgroups defined by microsatellite-stable or PIK3CA wild-type disease, cyclooxygenase-2 expression, CDX2 expression, tumor-infiltrating lymphocyte levels, or prediagnosis aspirin use.

The investigators concluded: “The association of aspirin use with colorectal cancer survival is stronger in patients with CD274-low tumors than CD274-high tumors. Our findings suggest a differential antitumor effect of aspirin according to immune checkpoint status.”

The study was supported by National Institutes of Health grants, Dana-Farber Harvard Cancer Center, Project P Fund, The Friends of the Dana-Farber Cancer Institute, Bennett Family Fund, and the Entertainment Industry Foundation through National Colorectal Cancer Research Alliance.

Shuji Ogino, MD, PhD, of Brigham and Women’s Hospital and Harvard Medical School, is the corresponding author of the Journal of Clinical Oncology article.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.