Effect of acute aerobic exercise before immunotherapy and chemotherapy infusion in patients with metastatic non-small-cell lung cancer: protocol for the ERICA feasibility trial

Abstract

IntroductionPatients with metastatic non-small cell lung cancer (mNSCLC) suffer from numerous symptoms linked to disease and treatment which may further impair the patient’s overall condition. In addition to its benefits on quality of life and fatigue, physical exercise may improve treatment response, notably due to its known effects on the immune system. The ERICA study is designed to assess the feasibility of a supervised acute physical exercise therapy realised immediately prior immune-chemotherapy infusion in patients with mNSCLC. Secondary objectives will examine the effects of acute exercise combined with an unsupervised home-walking programme on clinical, physical, psychosocial and biological parameters.Methods and analysisERICA is a prospective, monocentric, randomised controlled, open-label feasibility study conducted at the Centre Léon Bérard Comprehensive Cancer Center (France). Thirty patients newly diagnosed with mNSCLC will be randomised (2:1 ratio) to the ‘exercise’ or the ‘control’ group. At baseline and during the last treatment cycle, participants in both groups will receive Physical Activity recommendations, and two nutritional assessments. In the exercise group, participants will receive a 3-month programme consisting of a supervised acute physical exercise session prior to immune-chemotherapy infusion, and an unsupervised home-based walking programme with an activity tracker. The acute exercise consists of 35 min interval training at submaximal intensity scheduled to terminate 15 min prior to infusion. Clinical, physical, biological and psychosocial parameters will be assessed at baseline, 3 and 6 months after inclusion. Biological measures will include immune, inflammatory, metabolic, oxidative stress biomarkers and molecular profiling.Ethics and disseminationThe study protocol was approved by the French ethics committee (Comité de protection des personnes Ile de France II, N°ID-RCB 20.09.04.65226, 8 December 2020). The study is registered on ClinicalTrials.gov (NCT number:NCT04676009) and is at the pre-results stage. All participants will sign an informed consent form. The findings will be disseminated in peer-reviewed journals and academic conferences.

Exercise to transform tumours from cold to hot and improve immunotherapy responsiveness

“…Therefore, importantly the utility of exercise as an effective intervention and an enhancer of immunotherapy responsiveness should be explored in ongoing human studies. ERICA is a prospective clinical trial looking into the practicalities and acceptability of undertaking exercise immediately prior to infusion of combination immunotherapy and chemotherapy in a French cohort of patients with metastatic NSCLC ( 53 ). Exploring the association between high intensity aerobic exercise and NK cell release in NSCLC, HI AIM is a randomised controlled trial that hypothesises augmented immunotherapy responses induced by exercise as a consequence of intratumoural and systemic immune cell influx ( 54 ).…”

Crosstalk between Exercise and Immunotherapy: Current Understanding and Future Directions

“…Currently, the majority of research on exercise and its impact on immunotherapy efficacy are conducted on animal models, with limited clinical data available. Existing randomized controlled trials primarily focus on the physiological and psychological effects of exercise on cancer patients receiving immunotherapy [ 15 – 17 ], as well as the changes regarding immune and inflammatory biomarkers in blood samples [ 18 , 19 ]. However, overall survival, PFS, and ORR are supposed to be considered to assess the long-term influence of immunotherapy in combination with exercise training on cancer patients [ 20 ].…”

Can Exercise Enhance the Efficacy of Checkpoint Inhibition by Modulating Anti-Tumor Immunity?

“…The ERICA study (NCT04676009), a prospective monocentric, randomized controlled open-label study, investigates the acute effects of one hour exercise before application of checkpoint inhibition (pembrolizumab) plus platinum-based duplet chemotherapy in 30 NSCLC patients. [ 171 ]. Patients conducted a three-month exercise program consisting of a supervised exercise session (35 min interval training at submaximal intensity) one hour before immune-chemotherapy infusion and an unsupervised home-based walking program recorded by an activity tracker.…”