Association of Geriatric Nutritional Risk Index With Immune Checkpoint Inhibitor Treatment Duration and Adverse Events in Lung Cancer

Abstract

Background/Aim: Compared to conventional cytotoxic anticancer agent-based therapy, treatment with immune checkpoint inhibitors (ICI) significantly prolongs overall survival. The Geriatric Nutritional Risk Index (GNRI) has been used as a new prognostic indicator in cancer. As nutritional status is associated with prognosis and indicates treatment response, we investigated the effect of the pretreatment GNRI on the (1) occurrence of ICI-induced immune-related adverse events (ir-AE) and ( 2) association with time to treatment failure (TTF) in ICI monotherapy for lung cancer. Patients and Methods: In this study, 127 patients with lung cancer who were treated with ICI monotherapy were retrospectively enrolled. Based on a cutoff value of 92 for the GNRI, we investigated intergroup differences in the occurrence of adverse events and their association with TTF in the High-GNRI (≥92) and Low-GNRI (<92) groups. For intergroup comparisons, we used the Student's t-test, Welch's t-test, Fisher's direct probability test, and Mann-Whitney's Utest, and factors with p<0.05 in the intergroup comparison were extracted as explanatory variables. Results: Based on the pretreatment GNRI, the median TTF was 5.1 months (95%CI=2.4-7.9 months) in the High-GNRI group and 2.3 months (95%CI=1.6-3.1 months) in the Low-GNRI group, with the High-GNRI group having a significantly longer TTF (p<0.01). The incidence of skin rash (p=0.0129) and pruritus (p<0.01) was significantly higher in the High-GNRI group. Conclusion: Pretreatment GNRI influences the continuation of ICI monotherapy. The High-GNRI group demonstrated a significantly higher frequency of skin lesions, which may have influenced the prolongation of TTF.In Japan, 126,548 new cases of lung cancer were reported in 2019 and 75,585 deaths in 2020; thus, lung cancer has the second highest incidence rate by cancer site and the highest cancer mortality rate (1). Lung cancer may be treated surgically if detected early; however, in case of metastasis or recurrence, drug therapy is the mainstay of treatment, wherein cytotoxic anticancer agents, molecular-targeted drugs, and immune-checkpoint inhibitors (ICI) are used. Thus, in the treatment of non-small cell lung cancer, molecular-targeted agents and ICI are the mainstay of treatment. In small cell lung cancer, although cytotoxic anticancer agents have been the mainstay of treatment for a long time, ICI can also be used (2). Nivolumab, pembrolizumab, atezolizumab, and durvalumab are used in the treatment of lung cancer. Treatment with ICI significantly prolongs overall survival compared to conventional treatment with cytotoxic anticancer agents (3-6). However, ICI treatment discontinuation or withdrawal occurs when the disease progresses or serious adverse events occur, which results in the difference in treatment duration. In addition, many cancers are more prevalent in the 60-70 age group and in older adults (1), who may, regardless of disease status, have reduced nutritional status. According to the "Summary of the Results of the National Hea...