A recent data analysis from a randomized trial involving stage 3 colon cancer patients at Dana-Farber Brigham Cancer Center indicates that patients showing signs of leftover cancer in their bloodstream after surgical removal of the tumor might see benefits from including celecoxib in their post-surgery care. The study found that patients who tested positive for circulating tumor DNA (ctDNA) in their blood generally had poorer outcomes. However, those treated with celecoxib, which is a non-steroidal anti-inflammatory medication, demonstrated marked improvements in their disease-free survival rates.
“This research is among the first to indicate that ctDNA status can help identify patients who are more likely to respond to a specific medication,” states Jonathan Nowak, MD, PhD, a pathologist at Dana-Farber Cancer Institute and Brigham and Women’s Hospital. He shared the study findings at the American Society of Clinical Oncology Gastrointestinal Cancers Symposium on January 25, 2025, in San Francisco, California.
“These results complement our previous discoveries that celecoxib enhances survival in patients with PIK3CA mutated colon cancer,” adds Jeffrey Meyerhardt, MD, MPH, the senior author and co-director of the Colon and Rectal Cancer Center at Dana-Farber Cancer Institute. “This research paves the way for developing a personalized treatment strategy for early-stage colon cancer patients.”
Initially, patients diagnosed with stage 3 colon cancer undergo surgery to eliminate the cancer from the colon and nearby lymph nodes. Following surgery, they generally receive adjuvant chemotherapy aimed at minimizing the risk of cancer recurrence. Unfortunately, in some cases, the cancer may return, making the patient potentially incurable. Dana-Farber is focused on discovering methods to enhance adjuvant therapies and prevent recurrence.
To examine the impact of celecoxib on disease-free survival in these patients, Meyerhardt and his team launched the CALGB (Alliance)/SWOG 80702 trial in 2010, collaborating with the Alliance for Clinical Trials in Oncology and the National Cancer Institute. The trial enrolled 2,526 participants from 2010 to 2015. After the initial treatment, patients were divided to receive adjuvant chemotherapy combining fluorouracil, leucovorin, and oxaliplatin (FOLFOX) for a duration of three or six months, either with or without daily celecoxib for three years. Those on celecoxib experienced a moderate advantage; nonetheless, the findings published in 2021 were not statistically notable.
Recent evidence proposes that anti-inflammatory drugs could be beneficial for specific colon cancer patients, yet not for everyone. One explanation is that individuals testing positive for ctDNA shortly after surgery have a heightened risk of cancer recurrence and could gain from therapies beyond standard chemotherapy. This current study aimed to determine if anti-inflammatory drugs could help prevent relapse in patients who had positive ctDNA tests following their surgeries.
When designing the original celecoxib clinical trial a decade back, patients were evaluated pre- and post-surgery using imaging techniques, which can identify where cancer cells are grouped but lack detailed resolution. Today’s ctDNA tests offer a more precise analysis of whether any cancer remains after surgery by detecting minuscule tumor DNA fragments in the bloodstream.
The research team identified 1,011 out of the 2,526 trial participants who had consented to provide blood samples for research analysis. They conducted ctDNA tests on blood samples collected after surgery. This evaluation revealed that patients with positive ctDNA results typically had poorer outcomes. However, those with positive ctDNA who were given celecoxib along with standard chemotherapy showed significantly better disease-free survival compared to those only receiving standard chemotherapy. In patients with negative ctDNA tests, the difference between those taking celecoxib and those on a placebo was not significant.
“The analysis indicates that the combination of celecoxib and chemotherapy shows promising benefits for early-stage colon cancer patients who have positive ctDNA results after their primary treatment,” remark the researchers. “These findings, along with results from ongoing studies, will assist in determining which patients may gain from adding celecoxib to their standard therapies.”
Funding: The Alliance for Clinical Trials in Oncology Foundation, National Cancer Institute, Natera, Inc.
