Researchers have found that administering the anti-inflammatory drug celecoxib after surgery may improve disease-free survival in a subset of patients with PIK3CA-mutated stage III colorectal cancer, according to a study published by Nowak et al in the Journal of Clinical Oncology. The findings highlight a potential breakthrough in personalized cancer treatment.
Background
Following primary treatment for stage III colorectal cancer, patients typically receive adjuvant chemotherapy intended to reduce the risk of cancer recurrence. In patients whose cancer recurs, treatment options are often limited.
Prior research has found that adjuvant anti-inflammatory prostaglandin inhibitors—which included celecoxib—may improve survival in patients with PIK3CA-mutated colorectal cancer.
Previous Findings
In the Alliance 80702 trial, published by Meyerhardt et al in JAMA in 2021, researchers enrolled 2,526 patients between 2010 and 2015. Following treatment, they randomly assigned the patients to receive adjuvant chemotherapy with fluorouracil, leucovorin, and oxaliplatin (FOLFOX) for 3 to 6 months with or without daily celecoxib for 3 years.
The patients who received celecoxib demonstrated a moderate benefit; however, the results were not deemed statistically significant.
During the execution of that trial, new evidence suggested that anti-inflammatory drugs might benefit some patients with colorectal cancer, but not others. For instance, in an observational study from 2012, published by Liao et al in The New England Journal of Medicine, researchers observed that the patients with colorectal cancer who regularly used aspirin—a drug with a similar mechanism of action as celecoxib—had longer survival, but only if they had PIK3CA-mutated disease. Other observational studies conducted since then have supported this association.
“We needed to do a subgroup analysis of the Alliance 80702 trial data to determine if PIK3CA mutations are a predictor of response to celecoxib,” noted lead study author Jonathan Nowak, MD, PhD, a molecular and gastrointestinal pathologist at Brigham and Women’s Hospital and Dana-Farber as well as an investigator at the Hale Family Center for Pancreatic Cancer Research at Dana-Farber.
Study Methods and Results
Researchers performed whole-exome sequencing on 1,200 tumor samples from patients who participated in the Alliance 80702 trial. They found that 22% of the patients had PIK3CA-mutated colorectal cancer. Among these patients, those who received celecoxib experienced longer survival compared with the patients without PIK3CA mutations who received celecoxib.
In this analysis, the patients’ risk of dying was reduced by about 50% and by about 60% when excluding those who were using low-dose aspirin for reasons not related to their cancer treatment. Disease-free survival was also improved but did not reach statistical significance.
Conclusions
“These findings strengthen a growing body of evidence suggesting that prostaglandin inhibitors could benefit a subgroup of patients with [colorectal] cancer. They suggest a potential personalized approach to additional therapy for patients with early-stage [colorectal] cancer,” explained senior study author Jeffrey Meyerhardt, MD, MPH, FASCO, Co-Director of the Colon and Rectal Cancer Center at Dana-Farber Cancer Institute. “If these results are confirmed in other ongoing studies, it will be important for physicians to understand the genetics within the tumors of patients with early-stage [colorectal] cancer to determine which patients may benefit from celecoxib in addition to other standard treatments,” he concluded.
Disclosure: The research in this study was funded by the National Institutes of Health, the Alliance for Clinical Trials in Oncology Foundation, the Karen Guo Colon Cancer Fund, the Douglas Gray Woodruff Chair in Colorectal Research Fund, and the Stone Research Fund. For full disclosures of the study authors, visit ascopubs.org.
