The CHALLENGE Trial Helps Redefine Adjuvant Therapy With Exercise in CRC

Nicholas James Hornstein, MD, PhD, discussed results from the phase 3 CHALLENGE trial (NCT00819208) that were presented at the 2025 American Society of Clinical Oncology Annual Meeting. According to Hornstein, this trial has garnered significant attention, particularly for its exploration of exercise as a therapeutic intervention in colorectal cancer (CRC).

This randomized study enrolled patients who had undergone resection for localized colon cancer and assigned them to one of 2 arms: a regimented exercise program with a personal trainer or an educational arm providing general advice on the benefits of exercise.

Hornstein, an assistant professor at the Donald and Barbara Zucker School of Medicine of Hofstra University and Northwell Health, noted that the study yielded remarkably positive results. The disease-free survival (DFS) in the group that participated in the structured exercise intervention was substantially higher. The observed DFS benefit from exercise was, according to Hornstein, surprisingly even greater than that seen with oxaliplatin chemotherapy, a standard component of adjuvant treatment for colorectal cancer.

Transcript:

This was not a plenary session. This was an oral [session], and this study has gotten a lot of press. I’ve heard the saying [that] exercise is the best medicine, and this was explored in the clinical trial. This was a randomized trial taking patients who [had] status [of] postresection for localized colon cancer, and it put them into 2 buckets. One, you get a personal trainer and regimented exercise over the course of a week. The other was that you got [educated] about exercise. Somebody sat down and said, “Hey, exercise is great. You should think about it.” [They’re] very different interventions. A lot of people would have expected that this wouldn’t be that positive of a study, but when they randomized the data, the DFS in the group who did exercise as their intervention was drastically higher.

Comparing this with what we normally get, things like oxaliplatin and chemotherapy, there was a higher DFS benefit with exercise than there was with oxaliplatin. This is shocking in terms of the degree of benefit that was observed in this study. Most people would have said, “Oh, yeah, there probably is going to be some benefit to exercise,” but the fact that this is looking to be on the same level as one of our chemotherapy moieties is incredible. This was an interesting study. It is something that I am discussing with all my patients now in the adjuvant setting. I’ve even had some patients who have said, “Hey, can you write me a prescription for a gym pass membership? Can you see if we can get this covered?” Because to them and me, this is something that needs to be incorporated into our daily practice now, and a lot of patients can benefit. It’s just nice to have a study to point to and say, “Exercise is worth it.”

Reference

Booth CM, Vardy JL, O’Callaghan CJ, et al. A randomized phase III trial of the impact of a structured exercise program on disease-free survival (DFS) in stage 3 or high-risk stage 2 colon cancer: Canadian Cancer Trials Group (CCTG) CO.21 (CHALLENGE). J Clin Oncol. 2025;43(17):LBA3510. doi:10.1200/JCO.2025.43.17_suppl.LBA3510