Physical activity and checkpoint inhibition: association with toxicity and survival 

While animal experiments suggest beneficial effects of physical activity (PA) on anti-tumor immunity, little is known about the effects of PA on immune checkpoint inhibitor (ICI) toxicity and effectiveness in humans. We assessed the association of PA with immune-related adverse events (irAE) and survival in patients undergoing ICI.

Patients receiving ICI who completed the PA-SQUASH questionnaire at start of treatment as part of the prospective UNICIT study in an academic hospital were included. PA was quantified by calculating total Metabolic Equivalent Task hours per week (total PA) and hours per week of moderate-to-vigorous-intensity PA during sport and leisure time (MVPA-SL). Associations of PA with severe irAE occurrence within one year and overall survival (OS) were evaluated using logistic regression and Cox proportional hazard regression, respectively, with adjustment for probable confounders.

In total, 251 patients were included with a median follow-up of 20 months. Moderate and high levels of total PA were associated with lower odds of severe irAE occurrence compared to low levels of total PA (adjusted OR: 0.34 (95%CI 0.12-0.90) and 0.19 (95%CI 0.05-0.55), respectively). Moderate and high levels of total PA were also associated with prolonged survival (adjusted HR: 0.58 (95%CI 0.32-1.04) and 0.48 (95%CI 0.27-0.89), respectively). Similar associations were observed in patients who performed more MVPA-SL.

Higher physical activity levels at start of ICI treatment are associated with lower risk of severe irAEs and probably prolonged survival. Randomised controlled trials are needed to investigate whether patients indeed benefit from increasing PA levels after diagnosis.