Biomarkers and factors in small cell lung cancer patients treated with immune checkpoint inhibitors: A meta-analysis.

Abstract

The aim of this meta-analysis was to summarize the available results of immunotherapy predictors for small cell lung cancer (SCLC) and to provide evidence-based information for their potential predictive value of efficacy. We searched PubMed, EMBASE, Web of Science, The Cochrane Library, and ClinicalTrials (from January 1, 1975 to November 1, 2021). The hazard ratios (HR) and its 95% confidence intervals (CIs) and tumor response rate of the included studies were extracted. Eleven studies were eventually included and the pooled results showed that programmed cell death ligand 1 (PD-L1) positive: objective response rate (ORR) (relative risk [RR]=1.39, 95% CI [0.48, 4.03], p=0.54), with high heterogeneity (p=0.05, I2 = 56%); disease control rate [DCR] (RR=1.31, 95% CI [0.04, 38.57], p=0.88), with high heterogeneity (p=0.04, I2 = 75%); overall survival (OS) (HR=0.89, 95% CI [0.74, 1.07], p=0.22); and progression-free survival (PFS) (HR=0.83, 95% CI [0.59, 1.16], p=0.27), with high heterogeneity (p=0.005, I2 = 73.1%). TMB-High (TMB-H): OS (HR=0.86, 95% CI [0.74, 1.00], p=0.05); PFS (HR=0.71, 95% CI [0.6, 0.85], p< 0.001). Lactate dehydrogenase (LDH) >upper limit of normal (ULN): OS (HR=0.95, 95% CI [0.81, 1.11], p=0.511). Asian patients: OS (HR=0.87, 95% CI [0.72, 1.04], p=0.135); White/Non-Asian patients: OS (HR=0.83, 95% CI [0.76, 0.90], p < 0.001). Liver metastasis patients: OS (HR=0.93, 95% CI [0.83, 1.05], p=0.229); PFS (HR=0.84, 95% CI [0.67, 1.06], p=0.141). Central nervous system (CNS) metastasis patients: OS (HR=0.91, 95% CI [0.71, 1.17], p=0.474); PFS (HR=1.03, 95% CI [0.66, 1.60], p=0.903). The available research results do not support the recommendation of PD-L1 positive and TMB-H as predictors for the application of immune checkpoint inhibitors (ICIs) in SCLC patients. LDH, baseline liver metastasis and CNS metastasis may be used as markers/influencing factors for predicting the efficacy of ICIs in SCLC patients. Non-Asian SCLC patients had better efficacy with ICIs in our results.