Cachexia - sarcopenia as a determinant of disease control rate and survival in non-small lung cancer patients receiving immune-checkpoint inhibitors

Abstract Purpose The metabolic changes associated with cachexia – sarcopenia syndrome might down-regulate antitumor immunity. We hypothesized that this syndrome reduces efficiency of immune checkpoint inhibitors (ICPI) in non-small cell lung cancer (NSCLC). Methods The records of 142 consecutive NSCLC patients receiving first- or second-line anti-Programmed cell death protein 1) ICPI were reviewed. Response evaluation according to Response Evaluation Criteria in Solid Tumors 1.1 was performed at the eighth week of immunotherapy. Pretreatment cachexia was defined as a body-weight loss of 5% or more in the previous 6 months. Sarcopenia was estimated with the third lumbar skeletal muscle mass index (mSMI) and was evaluated before immunotherapy and at the eighth week. A decrease by 5% or more of the mSMI was considered as an evolving sarcopenia. The endpoints were disease control rate (DCR), progression-free (PFS) and overall survival (OS).Logistic regression model and Cox model took into account others covariables known to influence ICPI efficiency, particularly Programmed Death –Ligand 1 tumor cell score, Eastern Cooperative Oncology Group performance status and common somatic mutational status. Results In multivariate analysis, cachexia – sarcopenia syndrome reduced the probability of achieving a disease control and were associated with a shorter survival. Patients without cachexia had a better probability to achieve disease control in comparison with those who did not experience cachexia (59.9% and 41.1%, respectively; odds ratio 95% (confidence interval [95%CI]): 2.60 (1.03 - 6.58)). Patients with cachexia had a shorter OS when compared with those without cachexia (hazard ratios [HR] (95%CI): 6.26 (2.23 - 17.57)). Patients with an evolving sarcopenia had a shorter PFS and OS, with HR (95%CI): 2.45 (1.09 - 5.53) and 3.87 (1.60 - 9.34) respectively. Conclusion Cachexia – sarcopenia syndrome negatively influences patients’ outcome during anti-PD-1 ICPI therapy.