Prognostic Value of the Lung Immune Prognostic Index May Differ in Patients Treated With Immune Checkpoint Inhibitor Monotherapy or Combined With Chemotherapy for Non-small Cell Lung Cancer

Abstract

Background Lung immune prognostic index (LIPI) status was recently developed to predict responses to immune checkpoint inhibitor (ICI) treatments. However, it is unclear whether LIPI is a prognostic index for both patients treated with ICI monotherapy and patients treated with ICIs combined with chemotherapy (ICIs CC). Methods This retrospective study established the patterns of LIPI in Chinese patients with advanced non-small cell lung cancer. Lung immune prognostic index based on the derived neutrophil-to-lymphocyte ratio greater than 3 and lactate dehydrogenase greater than the upper limit of normal was developed to characterize good, intermediate, or poor LIPI status. Associations between LIPI status and progression-free survival (PFS) and overall survival (OS) were analyzed. Kaplan–Meier curves and Cox proportional hazards models were used to determine survival differences. Results Three hundred thirty patients were included in this study. Of these patients, 216 received ICI monotherapy and 114 received ICIs CC. A good LIPI status was associated with better PFS (6.1 months vs. 2.3 months vs. 2.1 months, P = 0.023) and OS (24.2 months vs. 14.5 months vs. 9.3 months, P < 0.001) in ICI monotherapy compared to intermediate or poor LIPI status. No differences in PFS (17.9 vs. 9.9 months vs. 7.6 months, P = 0.355, respectively) and OS ( P = 0.346) were observed in patients who received ICIs CC. Moreover, we found that patients who had an improved LIPI status compared with the baseline value had a longer PFS with ICI monotherapy and LIPI intermediate status (8.4 months vs. 2.1 months vs. 1.4 months, P < 0.001). However, in patients treated with ICIs CC, these dynamic changes were not observed ( P = 0.444). Conclusions Lung immune prognostic index status and dynamic changes in LIPI could be prognostic markers of treatment response to ICI monotherapy, but not to ICIs CC. In particular, good LIPI status was associated with a better clinical outcome compared with intermediate and poor LIPI status in ICI monotherapy treatment.

The Prediction Potential of the Pretreatment Lung Immune Prognostic Index for the Therapeutic Outcomes of Immune Checkpoint Inhibitors in Patients With Solid Cancer: A Systematic Review and Meta-Analysis

“…Neither of them is heterogeneous (I 2 = 0.0%, P=0.646; I 2 = 0.0%, P=0.639). However, the LIPI score may not predict therapeutic outcomes in cancer patients receiving chemo-immunotherapy ( 26 ). The sensitivity analysis also showed that no individual study influenced the pooled effects on OS and PFS ( Supplementary Figures 6 and 7 ).…”

“…After reviewing the remaining 39 articles via the full-text view, 27 full-text articles were excluded due to lack of intended outcomes (OS, PFS), HR with 95% CI or repeatedly published studies. Finally, 12 studies published between 2018 and 2020 were included in this analysis (11)(12)(13)(14)(19)(20)(21)(22)(23)(24)(25)(26).…”

Value of the Lung Immune Prognostic Index in Patients with Non-Small Cell Lung Cancer Initiating First-Line Atezolizumab Combination Therapy: Subgroup Analysis of the IMPOWER150 Trial

“…LIPI is calculated based on pre-treatment derived neutrophil to lymphocyte ratio (dNLR) and lactate dehydrogenase (LDH) levels. It has been demonstrated as a prediction tool that differentiates likely prognosis of patients with NSCLC initiating ICI treatment [ 8 , 11 , 12 , 13 , 14 , 15 , 16 ]. Studies have also demonstrated that LIPI may differentiate prognosis in patients treated with ICIs in other cancer types, including breast cancer, hepatocellular carcinoma, melanoma, renal cell carcinoma, small cell lung cancer, and urothelial carcinoma [ 12 , 17 , 18 , 19 , 20 ].…”

“…In addition to behaving as a prognostic biomarker, LIPI has been proposed as a method to classify patients subgroups with disparities in ICI treatment efficacy (i.e., a predictive biomarker) [ 13 ], albeit findings have been conflicting [ 8 , 14 , 15 , 21 , 22 ]. To date, there is minimal information of the prognostic performance of LIPI in patients with NSCLC initiating first-line, combination ICI approaches [ 11 , 12 ], and there is no information on treatment efficacy across LIPI defined subgroups in this cohort.…”

Prognostic Nutritional Index and Lung Immune Prognostic Index as Prognostic Predictors for Combination Therapies of Immune Checkpoint Inhibitors and Cytotoxic Anticancer Chemotherapy for Patients with Advanced Non-Small Cell Lung Cancer

“…In the original report on LIPI, they concluded that pretreatment LIPI was correlated with worse outcomes of ICI monotherapy, but not of chemotherapy [ 12 ]. Moreover, one report, which retrospectively analyzed 114 patients with advanced NSCLC, has concluded that LIPI could not be a prognostic marker of treatment response to ICIs combined with chemotherapy [ 16 ]. In contrast, the subgroup analysis of the IMPOWER150 trial analyzed 1148 participants and concluded that LIPI identified subgroups with significantly different survival following first-line Atezo combination therapy initiation for chemotherapy-naive, metastatic non-squamous NSCLC [ 17 ].…”