Endocrine Abstracts

Introduction: Immune checkpoint inhibitors (ICI) show promising efficacy in the treatment of a wide range of advanced cancers, butlong-term response is currently limited to a subset of patients. Sarcopenia is a condition characterized by loss of skeletal muscle mass and decreased muscle function which occurs in approximately 50% of advanced cancer patients,related to malnutrition, inflammation, and treatments.

Objective: The aim of this prospective observational study was to investigate the relationship between sarcopenia (evaluated using DXA scan) and PD-1 inhibitors outcomes, in terms of OS and PFS, in patients with advanced NSCLC.

Materials and methods: 41 stage IV NSCLC patients about to start anti PD-1, were enrolled from the Policlinico Umberto I outpatient Oncology (May 2017-September 2019). Routine blood test, endocrine, inflammatory and body composition evaluation with dual-energy X-ray absorptiometry (DXA) were performed at baseline. aLM cut-offs to define sarcopenia were ≤7.23 kg/m² in men and ≤5.67 kg/m² in women. Patients were divided into two groups based on best responseusing RECIST criteria 1.1:clinical benefit(CB)group (including complete, partial response or stable disease), and progression disease (PD) group. The statistical analysis was carried out with non-parametric tests and results are reported as medianand interquartile range. Ethics Committee approval number 4946.

Results: Overall 17/41 patients (41.5%) resulted sarcopenic based on aLMscore. Specifically, a significant higher number of patients had sarcopenia in the PD group compared to CB. Nogender difference was found regarding prevalence of sarcopenia (P = 0.732). aLM waslower in PD vs CBgroup: PD = 6.11 kg/m² (3.8;6.4) vs CB = 7.6 kg/m² (5.7;7.9), P = 0.046. As a matter of fact, lean mass was lower in PD vs CB: PD = 36.3 kg (13.05;40.92) vs CB = 51.80 kg (39.45;52.93), P = 0.042. Patients with sarcopenia showed significantly worse PFS (4.9 months, 95% CI : 0.0–14.1, P = 0.03) and worse OS (10.9 months, 95% CI : 2.6–19.2, P = 0.024) compared to subjects without sarcopenia. In addition, considering inflammatory biomarkers, patients with sarcopenia showed higher NLR ratio (P = 0.005), higher LLR ratio (P = 0.005), higher CRP (P = 0.021) compared to sarcopenic patients.

Conclusions: Subjects with sarcopenia showed worse PFS and OS compared to subjects without sarcopenia. This supports the idea that sarcopenia can reflect the increased metabolic activity of more aggressive tumors, which involves systemic inflammation and muscle wasting. Furthermore, sarcopenic patients showed higher levels of inflammatory biomarkers compared to non-sarcopenic patients. Assessment ofsarcopenia may help identify patients more likely to achieve a better response to anti PD-1 in routine clinical practice.