Systemic Inflammation/Nutritional Status Scores Are Prognostic but Not Predictive in Metastatic Non-Small-Cell Lung Cancer Treated with First-Line Immune Checkpoint Inhibitors

Abstract

Biomarkers of systemic inflammation/nutritional status have been associated with outcomes in advanced-stage non-small-cell lung cancer (NSCLC) treated with immune checkpoint inhibitors (ICIs). However, most of them were not tested in cohorts of patients treated with ICIs in combination with chemotherapy (CT) (ICI+CT) or with CT alone, making it impossible to discriminate a predictive from a prognostic effect. We conducted a single-center retrospective study to search for associations between various baseline biomarkers/scores that reflected the systemic inflammation/nutritional status (Lung Immune Prognostic Index, Modified Lung Immune Prognostic Index, Scottish Inflammatory Prognostic Score, Advanced Lung Cancer Inflammation Index, EPSILoN, Prognostic Nutritional Index, Systemic Immune-Inflammation Index, Gustave Roussy Immune Score, Royal Marsden Hospital Prognostic Score, Lung Immuno-oncology Prognostic Score 3, Lung Immuno-oncology Prognostic Score 4, score published by Holtzman et al., and Glasgow Prognostic Score) and outcomes in metastatic NSCLC treated in a first-line setting either with ICI in monotherapy (cohort 1; n = 75), ICI + CT (cohort 2; n = 56), or CT alone (cohort 3; n = 221). In the three cohorts, the biomarkers/scores were moderately associated with overall survival (OS) and progression-free survival (PFS). Their prognostic performance was relatively poor, with a maximum c-index of 0.66. None of them was specific to ICIs and could help to choose the best treatment modality. The systemic inflammation/nutritional status, associated with outcomes independently of the treatment, is therefore prognostic but not predictive in metastatic NSCLC.

Clinical Utility of Inflammatory and Nutritious Index as Therapeutic Prediction of Nivolumab plus Ipilimumab in Advanced Non-Small Cell Lung Cancer

“…Recently, Mahiat et al [6] reported that systemic inflammatory/nutritional status was moderately associated with outcome after ICI monotherapy, ICI plus platinum-based chemotherapy, and chemotherapy alone in Caucasian patients with advanced NSCLC; for immunotherapy, it was prognostic but not predictive. Seban et al [7] identified high NLRs, PLRs, and SIIs as independent prognostic factors for first-line PD-1 blockade treatment of advanced NSCLC.…”

“…Clinical and biological data (e.g., total protein, albumin, and CRP levels; white blood cell, neutrophil, platelet, and lymphocyte counts; and height and weight) were extracted from the medical records and analyzed. Six indices reflecting systemic inflammatory and nutritional status based on previous studies [6] were calculated at baseline within 1 week of the first cycle of each treatment. The inflammatory indices were as follows: (1) NLR = neutrophil count/lymphocyte count [7], (2) PLR = platelet count/lymphocyte count [7], and (3) SII = platelet count × neutrophil count/lymphocyte count [7].…”

“…The inflammatory indices were as follows: (1) NLR = neutrophil count/lymphocyte count [7], (2) PLR = platelet count/lymphocyte count [7], and (3) SII = platelet count × neutrophil count/lymphocyte count [7]. The nutritional indices were as follows: (1) prognostic nutritional index (PNI) = 10 × albumin (g/dL) + 0.005 × lymphocyte count [6], (2) advanced lung cancer inflammation index (ALI) = body mass index + albumin level (g/dL)/NLR [12], and (3) Glasgow prognostic score (GPS). The GPS was tabulated as follows: zero = no abnormal values (good), 1 = one abnormal value (intermediate), and 3 = two abnormal values (poor) [13].…”

“…Predicting Nivo-Ipi efficacy based on these data has several advantages: the data are readily available and can be economically and conveniently obtained. Recent studies have shown that inflammatory and nutritional indices in blood samples significantly predict PD-1 blockade efficacy [6, 7]. Inflammatory indices, such as the neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), and systemic immune-inflammation index (SII), were potential prognostic and predictive biomarkers in patients with Nivo-Ipi-treated melanoma [8] and metastatic renal cell carcinoma [9].…”

Soluble biomarkers to predict clinical outcomes in non-small cell lung cancer treated by immune checkpoints inhibitors

“…explored systemic inflammation/nutritional status (including PNI) as predictive factors in 3 metastatic NSCLC cohorts treated in the first line by ICI monotherapy (n=75), ICI combined with chemotherapy (n=56), or chemotherapy alone (n=221). Their results supported that systemic inflammation/nutritional status could be associated with the outcomes independently of the treatment, and were therefore prognostic but not predictive ( 59 ). The ICI efficacy predicted by PNI also seemed independent of PD-L1 expression, since no association between PD-L1 TPS and PFS/OS was reported while a lower PNI was significantly associated with shorter PFS (HR: 1.704, p<0.05) ( 60 ).…”