Improving aerobic capacity in patients with advanced non-small cell lung cancer: study protocol of the 3-armed randomized controlled BREATH trial

Background: Lung cancer is one of the most common cancers in Germany, with around 56,000 new cases diagnosed in 2020. Approximately 65% are diagnosed at advanced stages, where symptoms such as fatigue, pain, dyspnea, and weight loss are prevalent. These patients often suffer from cardiovascular and pulmonary comorbidities, which interact with treatment toxicity, outcome and increase treatment costs. Although exercise therapy is proven to alleviate cancer-related symptoms and to improve quality of life, current lung cancer treatment guidelines fail to adequately prioritize its crucial role.Methods: The Better symptom contRol with Exercise in pAtients wiTH advanced non-small cell lung cancer (BREATH) study is a prospective, three-arm randomized controlled trial (RCT) designed to assess the impact of exercise therapy on patients with advanced NSCLC (stage IIIB-IV) who are receiving first- or second-line systemic therapy) in the palliative setting. Patients are randomized in a 2:1:1 ratio into a control group (receiving exercise recommendations) or one of two intervention arms: endurance training and breathing exercise or combined endurance and resistance training. The intervention groups will exercise twice a week for 12 weeks. The control group participants will be randomized again in a 1:1 ratio into one of the two intervention arms after completion of the control period. The study will assess outcomes at baseline, 12 weeks, and 24 weeks. The primary outcome is improvement of aerobic capacity (VO ₂ peak). Secondary outcomes include quality of life, fatigue, adherence to exercise and adverse events. Patient representatives were involved in all stages of protocol development.Discussion: The BREATH study addresses a significant gap in the current management of advanced lung cancer treatment by evaluating the impact of different exercise treatment protocols to reduce symptoms and improve clinical outcome. The study design and exercise program aim to enhance adherence and optimize patient related outcomes. The results of the BREATH study have the potential to influence future guidelines and improve the management of patients with advanced NSCLC.Trial registration ClinicalTrials.gov NCT registered on the 18. April 2024 (NCT06374160)