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

Lin-Lu Li; Cheng-Feng Yu; Hong-Ting Xie; Zheng Chen; Bo-Hui Jia; Fei-Yu Xie; Ya-Fang Cai; Peng Xue; Shi-Jie Zhu

doi:10.1002/cam4.5800

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

Cancer Med. 2023 May;12(10):11211-11233. doi: 10.1002/cam4.5800. Epub 2023 May 10.

Authors

Lin-Lu Li^{1

2}, Cheng-Feng Yu¹, Hong-Ting Xie^{1

2}, Zheng Chen^{1

2}, Bo-Hui Jia³, Fei-Yu Xie^{1

2}, Ya-Fang Cai^{1

2}, Peng Xue¹, Shi-Jie Zhu¹

Affiliations

¹ Department of Oncology, Wangjing Hospital, China Academy of Chinese Medical Sciences, 100102, Beijing, China.
² Graduate School, Beijing University of Chinese Medicine, 100029, Beijing, China.
³ Beijing Sihui West District Hospital, 100082, Beijing, China.

Abstract

Objective: 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.

Methods: 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.

Results: 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).

Conclusion: 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.

Keywords: biomarkers; immune checkpoint inhibitors; meta-analysis; small cell lung cancer.

Publication types

Meta-Analysis
Research Support, Non-U.S. Gov't

MeSH terms

B7-H1 Antigen
Biomarkers
Carcinoma, Non-Small-Cell Lung*
Humans
Immune Checkpoint Inhibitors / therapeutic use
L-Lactate Dehydrogenase
Liver Neoplasms*
Lung Neoplasms* / drug therapy
Neoplasms, Second Primary*
Small Cell Lung Carcinoma* / drug therapy

Substances

Immune Checkpoint Inhibitors
B7-H1 Antigen
Biomarkers
L-Lactate Dehydrogenase