Effects of exercise on fatigue and health-related quality of life (HRQoL) in patients with metastatic breast cancer (mBC) – do the positive effects apply to all? The multinational randomized controlled PREFERABLE-EFFECT study

Background: The PREFERABLE‐EFFECT study (NCT04120298) was designed to assess effects of a 9‐month supervised exercise program in patients with mBC on fatigue, HRQoL and cancer‐ and treatment‐related side effects. Here we investigate whether exercise effects are consistent across subgroups of patients. Materials and Methods: PREFERABLE‐EFFECT is a multinational RCT including patients with mBC from five European countries (DE, PL, ES, SE, NL) and Australia. Participants were randomly assigned to usual care (UC) or a 9‐month supervised, combined aerobic and resistance exercise program (EX). All participants received general exercise advice (physical activity ≥30 min/day) and an activity tracker. Our primary outcomes physical fatigue (EORTC QLQ‐FA12 subscale) and HRQoL (EORTC QLQ‐C30 summary score), were assessed at baseline, 3, 6, and 9 months. Intervention effects (intention‐to‐treat) were determined by comparing the change from baseline to 3, 6 (i.e., primary endpoint) and 9 months between groups using mixed effects models for repeated measures, adjusted for baseline values of the outcome variable and stratification factors (line of treatment and study center). A significant improvement of either or both primary outcomes was considered as successful. Subgroup effects were investigated by adding interaction terms to the model for age, tumor receptor status, disease‐free interval and one relevant EORTC QLQ‐C30 symptom scale ‘pain’. Results: Between 2019–2022, we included 357 patients with mBC: 178 randomized to EX and 179 to UC. Patients were, on average, 55.4 years of age (SD = 11.1), most patients received 1st/2nd line of treatment at study enrollment (74.8%) and had bone metastases (73.9%). At 6 months, participation in the exercise program resulted in statistically significant positive effects on both primary outcomes, compared to UC: physical fatigue was lower (mean difference: −5.3, 95% CI −10.0; −0.6, effect size (ES) = 0.22) and HRQoL was better (+4.8, 2.2;7.4, ES = 0.33). We also found positive effects on numerous QLQ‐C30 scales, including pain (−7.1, −12.1; −1.9, ES = 0.28). These positive effects did not differ significantly as a function of tumor receptor status or disease‐free interval. Larger effects on HRQoL were found for patients who were younger (50 years (31%); +8.4, 3.2;13.6 vs ≥50 years; +3.3, 0.2;6.5) or reported pain above the clinically important threshold at baseline (58%) compared to patients without pain (+6.0, 2.0;10.0 vs +2.5, −0.8;5.7). Conclusion: Supervised exercise during palliative treatment led to beneficial effects on mBC patients’ fatigue and HRQoL. The effects were more pronounced in younger patients and patients who reported pain. Based on these findings, we recommend supervised exercise for all patients, and in particular those who report pain, as part of supportive care regimens during palliative treatment of mBC. No conflict of interest.