This observational study will investigate how immunotherapy affects physical fitness, quality of life, and treatment tolerance in adults with solid cancers. Immunotherapy can cause a range of side effects that impact daily functioning and may lead to treatment delays or early discontinuation. Physical fitness may influence how well patients cope with treatment, yet little is known about how fitness changes during immunotherapy or whether baseline fitness is linked to outcomes.
Participants will complete fitness testing using cardiopulmonary exercise testing (CPET) and quality-of-life questionnaires before starting immunotherapy and again 12 weeks later. Blood samples will also be taken, and long-term outcomes including survival, disease progression, and quality of life will be followed for up to 24 months. All cancer treatment will remain standard of care.
A small number of participants will be invited to take part in an optional research biopsy at week 12 to explore how physical fitness relates to changes in the tumour's immune environment.
The study will help researchers understand natural changes in fitness during immunotherapy, identify whether baseline fitness is associated with treatment tolerance or outcomes, and generate information needed to design future trials testing exercise-based interventions during immunotherapy.
Age ≥18 years
Histologically confirmed solid malignancy
Adjuvant: Single-agent anti-PD-1, anti-PD-L1, or anti-CTLA-4
Metastatic/Palliative: Single-agent or dual-agent anti-PD-1, anti-PD-L1, or anti-CTLA-4
Age <18 years
Prior adjuvant or neoadjuvant immunotherapy if all treatment-related adverse events have returned to baseline or stabilized
Prior anti-PD-1, anti-PD-L1, or anti-CTLA-4 therapy with at least 6 months since last dose and date of disease recurrence
Acute myocardial infarction within 6 weeks
Adults aged ≥18 years with histologically confirmed solid malignancies receiving immune checkpoint inhibitors (anti-PD-1, anti-PD-L1, or anti-CTLA-4) at University Hospital Southampton. Recruitment includes patients treated in the adjuvant setting with single-agent therapy after definitive local treatment, and patients in the metastatic or palliative setting receiving single- or dual-agent immunotherapy for advanced disease. The study uses a tumour-agnostic approach and includes any solid tumour for which immunotherapy is indicated. Examples include gastrointestinal, thoracic, skin, genitourinary, gynaecological, head and neck, breast, and other solid cancers treated with checkpoint inhibitors. Participants must have ECOG Performance Status 0-2 and be able to safely undertake cardiopulmonary exercise testing.
Other
Prospective
Observational Study - No Study Intervention
Other interventionThis is an observational study with no study-assigned interventions. All participants receive standard-of-care immunotherapy as prescribed by their treating oncologist. Immunotherapy may include anti-PD-1, anti-PD-L1, anti-CTLA-4 agents, or approved combination regimens. All doses, schedules, treatment modifications, delays, and discontinuations follow routine clinical practice and manufacturer guidance. Treatment decisions are made independently of the study. The study observes and records treatment administration, effects on fitness and quality of life, adverse events, and clinical outcomes without influencing clinical care.
Change in Oxygen Uptake at Anaerobic Threshold (VO₂ at AT)
Change in oxygen uptake at the anaerobic threshold measured using cardiopulmonary exercise testing (CPET). VO₂ at AT will be reported in millilitres per kilogram per minute (mL·kg-¹·min-¹).
Change in peak oxygen uptake (VO₂peak)
Change in peak oxygen uptake measured during CPET. Unit: mL·kg-¹·min-¹
Change in peak power output
Peak power output measured during CPET, reported in watts (W).
Change in ventilatory efficiency (VE/VCO₂ slope)
Ventilatory efficiency measured during CPET, reported as VE/VCO₂ slope (unitless ratio).
Cumulative Incidence of Immune-Related Adverse Events
Cumulative incidence of immunotherapy-related toxicity graded using Common Terminology Criteria for Adverse Events (CTCAE) v5.0 and Society for Immunotherapy of Cancer (SITC) immune-related adverse event criteria. Captured through systematic review during treatment phase. reported as CTCAE grade and/or proportion of participants with ≥Grade 3 toxicity (%).
Overall survival
Time from initiation of immunotherapy to death from any cause, assessed using routine clinical follow-up and medical records.
Disease-free survival
Time from initiation of immunotherapy to first documented disease recurrence, progression, or death from any cause, assessed using routine clinical follow-up and imaging. Unit of Measure: Time (months)
Event-free survival
Time from initiation of immunotherapy to disease progression, treatment discontinuation due to disease progression or treatment-related toxicity, or death from any cause, whichever occurs first, assessed using routine clinical follow-up and imaging. Unit of Measure: Time (months)
Disease progression status
Presence or absence of disease progression assessed using routine clinical imaging and clinical follow-up according to standard-of-care criteria. Unit of Measure: Categorical (progression / no progression)
Click on the lead sponsor to view all of their trials.
University Hospital Southampton NHS Foundation Trust
Lead sponsor
University of Southampton
Collaborator
National Institute for Health Research, United Kingdom
Collaborator
