SAN ANTONIO—A telephone-based intensified lifestyle intervention program helped patients with early breast cancer lose weight and may also help them live disease-free longer if they complete the program, according to an exploratory analysis from the SUCCESS C clinical trial (NCT00847444). The trial results were presented at the 2018 San Antonio Breast Cancer Symposium (Abstract GS5-03).
“There is evolving data that obesity and low physical activity are not only associated with an increased risk of cardiovascular disease and metabolic disorders, but also with a higher risk to develop malignancies, such as colon cancer and breast cancer,” said study presenter Wolfgang Janni, MD, Chair of the Department of Obstetrics and Gynecology, University of Ulm, Germany. “Furthermore, there is broad evidence that in patients who have already suffered breast cancer, a higher body mass index is associated with a less favorable prognosis compared to patients with normal body weight.
“However, up to date, there is little evidence from prospectively randomized studies to demonstrate that a systematic lifestyle intervention program can improve the prognosis in overweight breast cancer patients,” he noted.
SUCCESS C Study Details
The SUCCESS C study is a German, open-label, multicenter, randomized, controlled phase III trial with a two-by-two factorial design in patients with HER2-negative early breast cancer. For the first randomization, patients were assigned to one of two chemotherapy regimens: three cycles of epirubicin, fluorouracil, and cyclophosphamide followed by three cycles of docetaxel or six cycles of docetaxel plus cyclophosphamide.
For the second randomization, patients were assigned to the intervention group or control group. Patients in the intervention group participated in a 2-year standardized and structured telephone- and mail-based lifestyle intervention program with the goal of weight loss through diet and physical activities. Patients in the control group followed general recommendations for a healthy lifestyle for 2 years.
A total of 3,643 patients were recruited for the SUCCESS C study and randomly assigned to a chemotherapy regimen. For the second randomization, 2,292 patients were included with a body mass index range of 24.0-40.0 kg/m2; 1,146 patients were assigned to the lifestyle intervention group and 1,146 to the control group. The median follow-up was 64.2 months.
The intention-to-treat (ITT) analysis showed that patients in the intervention group lost an average of 1.0 kilograms (95% CI, –60 to –1.39), or 2.2 pounds, whereas the patients in the control group gained an average of 0.95 kilograms (95% CI, 0.61-1.30). No difference in disease-free survival (DFS) or overall survival (OS) was seen between the intervention and control group for both the univariate and multivariate analyses.
Overall, the trial had a 64.4 percent adherence rate, and on the basis of treatment groups, the intervention group had a lower completion rate compared to the control group (48% vs. 81%).
An unplanned, exploratory subgroup analysis of the lifestyle intervention group revealed differences based on completion. Those who completed the lifestyle intervention program had a longer median DFS (64.4 months vs. 58.9 months; p<0.001) and median OS (64.7 months vs. 63.3 months; p<0.001) than those who did not.
The exploratory analysis of only patients who completed the study further revealed that patients who completed the lifestyle intervention program had a longer median DFS than patients who completed general recommendations for a healthy lifestyle (HR=0.51; 95% CI, 0.33-0.78; p=0.002).
“This study should be interpreted with caution due to several limitations,” Janni warned. “Adherence to the intensified lifestyle intervention program was much lower than anticipated, which might compromise the validity of the study. While the ITT analysis did not demonstrate a difference between the two randomization arms, the result of the exploratory analysis might be, at least in part, caused by a bias between patients who completed and not completed the program.”
Study investigators found that in the intervention group, there were statistically significant differences between patients who completed the study and patients who did not for age, histological grading, and hormone receptor status.
“In conclusion, this analysis suggests that the completion of a systematic, telephone-based, lifestyle intervention program does positively impact body mass index and may improve in overweight patients the outcome in early breast cancer as indicated in previous trials,” Janni stated. “However, based on potential bias between completers and non-completers, the results of the exploratory interim analysis should be interpreted with appropriate caution.”
Eleni Andreopoulou, MD, breast oncologist at Weill Cornell Medicine and NewYork-Presbyterian Hospital in New York, told Oncology Times that this study “verifies” how weight control and increased physical activity are “extremely important” alongside conventional treatment to improve outcomes.
“We're recognizing how exercise in the long-term could improve metabolic conditions that can be adverse and promote cancer disease,” she noted, explaining that exercise decreases resistance to insulin, which facilitates better metabolism and is a favorable factor of improved outcomes.
“Patients need encouragement during the treatment,” Andreopoulou said, stating that a lifestyle intervention program that is monitored and clearly outlined should be integrated into a patient's care and made a part of the implementation of precision medicine.
Janni said that further analyses involving long-term follow-up, additional outcomes, and predictive factors for adherence are planned.
Christina Bennett is a contributing writer.