Exercise linked to longer PFS, fewer treatment-related toxicities in metastatic colorectal cancer
Patients with metastatic colorectal cancer who exercised regularly achieved longer PFS than those who did not, according to results of a companion study to the Cancer and Leukemia Group B/SWOG 80305 trial published in Journal of Clinical Oncology.
Physical activity also appeared associated with reduced risk for treatment-related adverse events among these patients.
Results showed even low-intensity exercise, such as 4 or more hours of walking per week, reduced risk for cancer progression or death by nearly 20% over the study interval.
“What we found was that people who engaged in some type of physical activity had a statistically significant improvement in PFS,” researcher Jeffrey A. Meyerhardt, MD, clinical director of the Gastrointestinal Cancer Center and deputy clinical research officer and Douglas Gray Woodruff chair in colorectal cancer research at Dana-Farber Cancer Institute, said in a press release.
In the nested prospective cohort study, Meyerhardt and colleagues analyzed data from 1,218 patients in the phase 3 Cancer and Leukemia Group B/SWOG 80405 trial of systemic therapy for metastatic colorectal cancer. Participants completed a validated questionnaire within a month of starting study treatment that asked about average physical activity over the prior 2 months. Based on responses, the researchers quantified physical activity by calculating metabolic equivalent task (MET) hours per week. They defined vigorous activity as any activity that required six or more METs, including running, bicycling, tennis, skiing and lap swimming. Activities defined as nonvigorous included walking, yoga and climbing stairs.
OS served as the primary endpoint of both the clinical trial and the nested study. PFS and first grade 3 or higher treatment-related adverse events served as secondary endpoints.
The researchers mitigated confounders related to poor or declining health by excluding patients who demonstrated progression or who died within 60 days of activity evaluation. They adjusted for known prognostic factors, comorbidities and weight loss using Cox proportional hazards regression analysis.
Median follow-up was 6.18 years, during which 1,056 patients demonstrated disease progression — 945 of whom later died. Additionally, 89 patients died without experiencing progression.
Compared with patients who participated in less than 3 MET hours per week of physical activity, patients with 18 or more MET hours per week demonstrated an adjusted HR for OS of 0.85 (95% CI, 0.71-1.02), which fell short of statistical significance, and an adjusted HR for PFS of 0.83 (95% CI, 0.7-0.99).
About two-thirds of patients (n = 795) experienced at least one grade 3 or higher treatment-related adverse event.
Compared with patients with fewer than 9 MET hours per week, those with 9 or more weekly MET hours demonstrated an adjusted HR for grade 3 or higher treatment-related adverse events of 0.73 (95% CI, 0.62-0.86). This finding retained statistical significance after adjustment for time between treatment initiation and completion of the physical activity questionnaire and exclusion of participants who completed the questionnaire more than 2 weeks after starting chemotherapy.
“Physically active patients in our study also appeared to tolerate chemotherapy better,” study author Brendan J. Guercio, MD, an internist affiliated with Brigham and Women’s Hospital, said in the release. “Total physical activity equivalent to 30 or more minutes of moderate daily activity was associated with a 27% reduction in severe treatment-related toxicities.”
The researchers noted several limitations to their study, including the potential differences between clinical trial participants and the general population, and trial participants who voluntarily complete questionnaires vs. other participants, as well as its reliance on self-reporting of physical activity.
In the press release, Meyerhardt noted that the study findings “help justify encouraging patients to exercise and referring patients to physical therapists or programs like the YMCA LIVESTRONG program that does small group training for patients with cancer.” -by Jennifer Byrne
Disclosures: Guercio reports institutional research funding from Bristol-Myers Squibb, Eli Lilly, Genentech, Pzer and Sano. Meyerhardt reports honoraria from Cota Healthcare, Ignyta and Taiho Pharmaceutical; a consultant/advisory role with Array BioPharma; institutional research funding from Boston Biomedical; and support from the Anonymous Family Fund for Innovations in Colorectal Cancer, Douglas Gray Woodruff Chair in Colorectal Cancer Research Fund, George Stone Family Foundation and Guo Shu Shi Fund. Please see the full study for all other researchers’ relevant financial disclosures.