Abstract GS02-10: Effects of a structured and individualized exercise program on fatigue and health-related quality of life in patients with metastatic breast cancer: the multinational randomized controlled PREFERABLE-EFFECT study
Authors: May Anne , Hiensch Anouk , Depenbusch Johanna , Schmidt Martina , Monninkhof Evelyn , Pelaez Mireia , Clauss Dorothea , Zimmer Philipp , Belloso Jon , Trevaskis Mark , Rundqvist Helene , Wiskemann Joachim , Muller Jana , Fremd Carlo , Altena Renske , Kufel-Grabowska Joanna , Bijlsma Rhode , van Leeuwen-Snoeks Lobke , Bokkel-Huinink Daan ten , Sonke Gabe , Mann Bruce , Francis Prudence , Richardson Gary , Álvarez Isabel , Malter Wolfram , Van der Wall Elsken , Aaronson Neil , Senkus Elżbieta , Urriticoechea Ander , Zopf Eva , Bloch Wilhelm , Stuiver Martijn , Wengström Yvonne , Steindorf Karen 
Published: May 2024

Abstract
INTRODUCTION:
Patients with metastatic breast cancer (mBC) often experience cancer- and treatment-related side effects that can impair daily life activities and health-related quality of life (HRQoL). Interventions are needed that improve HRQoL by alleviating fatigue and other side effects during palliative BC cancer treatment. Recent evidence-based international guidelines (ASCO, ACSM) recommend exercise for patients with BC during adjuvant treatment for reducing side effects. However, evidence of the effectiveness of exercise in patients with mBC is scarce. The PREFERABLE-EFFECT study (NCT04120298) was designed to assess the effects of a 9-month supervised exercise program in patients with mBC on fatigue, HRQoL, and other cancer- and treatment-related side effects.
METHODS:
PREFERABLE-EFFECT is a multinational, randomized controlled trial including patients with mBC from five European countries (Germany, Poland, Spain, Sweden, The Netherlands) and Australia. Participants were randomly assigned to usual care or an individualized, structured exercise program consisting of aerobic, resistance, and balance training. The first six months included twice weekly supervised exercise sessions of one hour. In the last three months, one supervised session was replaced by an unsupervised session, supplemented by an exercise App. All participants received general exercise advice (physical activity ≥ 30 min/day) and an activity tracker. Our primary outcomes, physical fatigue (subscale of the EORTC QLQ-FA12) and HRQoL (summary score of the EORTC QLQ-C30), were assessed at baseline, 3, 6, and 9 months. Among other physical fitness outcomes, maximal short exercise capacity was assessed with the Steep Ramp Test. The 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 separate mixed models for repeated measures, adjusted for baseline values of the outcome variable and stratification factors (mBC line of treatment (1st/2nd vs. 3rd or higher) and study center). A significant improvement of either or both primary outcomes (applying the Bonferroni-Holm method) was considered as successful.
RESULTS:
Between 2019-2022, we included 357 patients with mBC, with 178 patients randomized to the exercise intervention and 179 to usual care. Patients were, on average, 55.4 years of age (SD=11.1), most patients received 1st or 2nd line of treatment at study enrollment (74.8%) and had bone metastases (73.9%). At 6 months (primary endpoint), participation in the exercise intervention resulted in statistically significant positive effects on both primary outcomes, compared to usual care: physical fatigue was lower (mean difference: -5.3, 95% CI -10.0; -0.6, p=0.027, effect size (ES)=0.22) and HRQoL was better (+4.8, 95% CI 2.2; 7.4, p=0.0003, ES=0.33). Beneficial effects were also found at 3 months (physical fatigue: -3.4, -7.8; 1.0, ES=0.14 and QoL: 3.9, 1.5; 6.3, ES=0.27) and 9 months (physical fatigue: -5.6, -10.9; -0.4, ES=0.24 and QoL: +4.3, 1.4; 7.3, ES=0.31). Further, at the primary endpoint, we found positive exercise effects on physical fitness (+24.3 Watts, 15.5; 33.1, ES=0.42) and numerous QLQ-C30 scales, including social functioning (+5.5, 0.2; 10.8, ES=0.20), pain (-7.1, -12.1; -1.9, ES=0.28) and dyspnea (-7.6, -12.2; -3.0, ES=0.28). Two SAEs occurred (one wrist fracture and one sacral stress fracture), neither related to bone metastases.
CONCLUSION:
This large multinational study demonstrated significant beneficial effects of a supervised exercise intervention offered during palliative treatment on mBC patients’ fatigue, HRQoL, and other clinically relevant outcomes. Based on these findings, we recommend supervised resistance and aerobic exercise as part of supportive care regimens during palliative treatment of mBC.
Citation Format: Anne May, Anouk Hiensch, Johanna Depenbusch, Martina Schmidt, Evelyn Monninkhof, Mireia Pelaez, Dorothea Clauss, Philipp Zimmer, Jon Belloso, Mark Trevaskis, Helene Rundqvist, Joachim Wiskemann, Jana Muller, Carlo Fremd, Renske Altena, Joanna Kufel-Grabowska, Rhode Bijlsma, Lobke van Leeuwen-Snoeks, Daan ten Bokkel-Huinink, Gabe Sonke, Bruce Mann, Prudence Francis, Gary Richardson, Isabel Álvarez, Wolfram Malter, Elsken Van der Wall, Neil Aaronson, Elżbieta Senkus, Ander Urriticoechea, Eva Zopf, Wilhelm Bloch, Martijn Stuiver, Yvonne Wengström, Karen Steindorf. Effects of a structured and individualized exercise program on fatigue and health-related quality of life in patients with metastatic breast cancer: the multinational randomized controlled PREFERABLE-EFFECT study [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr GS02-10.