Tumour PD-L1 Expression in Small-Cell Lung Cancer: A Systematic Review and Meta-Analysis

Acheampong, Emmanuel; Abed, Afaf; Morici, Michael; Bowyer, Samantha; Amanuel, Benhur; Lin, Weitao; Millward, Michael; Gray, Elin S.

doi:10.3390/cells9112393

Cited by 47 publications

(41 citation statements)

References 90 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Furthermore, the positive group for 1/3 PD-L1 assays was observed in 31 (52.5%) of the total of 59 patients with SCLC. A recent meta-analysis of PD-L1 expression in SCLC, which included 27 studies enrolling a total of 2,792 patients, reported that the pooled estimate of PD-L1 expression was 26.0% (19). However, there were large differences in the rate of PD-L1 expression between the studies included, varying from 0% to 82.8%.…”

Section: Discussionmentioning

confidence: 99%

“…However, evidence of clinical impact as a predictive and/or prognostic biomarker of PD-L1 expression in SCLC is scarce and conflicting. Recent meta-analyses of clinical impact of PD-L1 expression in SCLC revealed inconsistent results (18,19). Thus, the association of PD-L1 expression in SCLC with clinicopathological factors warrants further investigation.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

The clinical impact of three validated PD-L1 immunohistochemistry assays as a prognostic factor in small cell lung cancer

Lee

Lim

Ryu

et al. 2021

Transl Lung Cancer Res

View full text Add to dashboard Cite

Background: Evidence of the clinical impact of programmed death-ligand 1 (PD-L1) expression in small cell lung cancer (SCLC) is scarce and conflicting, even though atezolizumab became the first PD-L1 inhibitor approved by the US Food and Drug Administration (FDA) in recent years for the initial treatment of extensive-stage (ES)-SCLC.Methods: We investigated PD-L1 expression in SCLC tumors using the three validated PD-L1 immunohistochemistry (IHC) assays (SP263, SP142, and 22C3) and assessed the correlation between PD-L1 expression and clinicopathological factors to determine the prognostic value of PD-L1 expression. The three PD-L1 IHC analyses were prospectively used to assess tumor samples of patients with SCLC at diagnosis.Results: Of the total of 59 patients, 47 patients received the active treatment beyond platinum-based chemotherapy at our institution. PD-L1 expression was positive in 39.0% with SP263, 37.3% with SP142, and 22.0% with 22C3. In a univariate analysis, the positive result of at least one of the three PD-L1 assays and the positive result of the SP142 assay were associated with longer overall survival (OS). A multivariable analysis confirmed that performance status, stage, and the SP142 assay were independent predictors of OS.In subgroup analysis, these results revealed more significant prognostic factors in ES than in limited-stage (LS). In patients with SCLC, especially those with ES, the expression of the SP142 assay is a significant independent prognostic factor.Conclusions: Although these results need to be further validated in larger cohorts, this information will benefit clinicians and patients in determining the immunotherapy for patients with ES-SCLC.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

The clinical impact of three validated PD-L1 immunohistochemistry assays as a prognostic factor in small cell lung cancer

Lee

Lim

Ryu

et al. 2021

Transl Lung Cancer Res

View full text Add to dashboard Cite

show abstract

“…Although positive PD-L1 expression appears to show better OS in SCLC patients, using it as a reliable predictive marker requires further large scaled studies. In a meta-analysis, the pooled HR of all studies was 0.86 (95% CI: 0.49-1.50, P=0.588) indicating that positive PD-L1 expression demonstrated a trend towards longer OS in SCLC patients (14). However, in the Checkmate 032 study, only 17% of patients had ≥1% PD-L1 expression and 5% had ≥5% PD-L1 expression, and the response to nivolumab monotherapy or a combination with ipilimumab occurred irrespective of the PD-L1 expression levels (21).…”

Section: Pd-l1 and Pd-1 Expressionmentioning

confidence: 99%

“…However, despite some observed correlations, there is a lack of concrete support for the use of PD-L1 expression levels in SCLC as a predictive biomarker for immunotherapy response (29). First, the pooled prevalence of PD-L1 expression is lower compared to those reported in non-small cell lung cancer (NSCLC), which are influenced by IHC evaluation cut-off values, PD-L1 staining pattern, the quality of the study's methodological characteristics, specimen acquisition, and other technical problems such as antibody staining and tissue fixation (14,30,31). Second, PD-L1 expression heterogeneity is not fully captured by small piece of tissue.…”

Section: Pd-l1 and Pd-1 Expressionmentioning

confidence: 99%

“…The addition of atezolizumab to the traditional etoposide-carboplatin regimen, followed by atezolizumab maintenance until progression, has shown a superior median OS of 12.3 months compared to 10.3 months in the placebo group, and a median progression free-survival (PFS) of 5.2 months compared to 4.3 months in the placebo group (12). In patients with advanced SCLC who were treated in CheckMate 032, the 2-year overall survival rate was 26% among those treated with nivolumab plus ipilimumab, compared to 14% in the nivolumab monotherapy group (14). This treatment was particularly enhanced in patients with high tumor mutation burden (TMB) (15).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

A narrative review of current and potential prognostic biomarkers for immunotherapy in small-cell lung cancer

Lim¹,

Kang²

2021

Ann Transl Med

View full text Add to dashboard Cite

Small-cell lung cancer (SCLC) is a highly invasive and rapidly proliferating pathologic subtype that accounts for 13-15% of all lung cancer cases. Recently in extensive-stage SCLC, treatments that combine immunotherapy and chemotherapy showed increased efficacy compared to chemotherapy alone in several trials. However, the combination of immunotherapy and conventional chemotherapy regimens was introduced only recently for extensive-stage SCLC, with relatively little real-world data. The demand for reliable biomarkers that can predict the efficacy of immunotherapy in SCLC is high. Several studies evaluated various parameters including programmed cell death ligand-1 (PD-L1) expression, tumor mutation burden (TMB), gene expression profiling, autoantibody, and blood cytokines for predictive value for response to immunotherapy in SCLC. Despite some observed correlations, there is a lack of concrete support for the use of PD-L1 expression levels for readily available biomarker. High TMB in combination with smoking history is predictive of a better response to immunotherapy, but validation of cutoffs and testing methods is necessary before it can be widely applied in clinical settings. Other candidate biomarkers such as immune cell distribution among tumor microenvironment, and systemic inflammatory markers can also be evaluated, after an accumulation of real-life data from SCLC patients under immunotherapy.

show abstract

Mutational landscape of homologous recombination‐related genes in small‐cell lung cancer

Zhang²,

Zhang

et al. 2022

Cancer Medicine

View full text Add to dashboard Cite

Background Homologous recombination deficiency (HRD) is a well‐known biomarker which could predict poly‐ADP ribose polymerase 1 (PARP) inhibitor and platinum drug response. As an aggressive cancer, small‐cell lung cancer (SCLC) is sensitive to platinum drugs, but relapse occurs rapidly. Herein, we aim to illustrate the genomic alteration patterns of homologous recombination repair (HRR)‐related genes in a Chinese SCLC cohort and further analyze the relationship among HRR gene mutations and known biomarkers of immune checkpoint inhibitor (ICI) response, including tumor mutation burden (TMB) and programmed cell death‐ligand 1 (PD‐L1) expression. Methods Next‐generation sequencing (NGS)‐based target capture sequencing of 543 cancer‐related genes was performed to analyze the genomic profiles of 133 Chinese SCLC patients, and TMB was calculated. PD‐L1 expression was evaluated in 90 out of 133 patients using the SP142 PD‐L1 immunohistochemistry assay. Results Among the 133 patients with SCLC, 47 (35.3%) had HRR gene mutations. ATM (8.3%) was the most frequently mutated HRR gene in the cohort, followed by NBN (4.5%). Pathogenic somatic and germline mutations of HRR genes were identified in 11 (23.4%) and 4 (8.5%) patients, respectively. HRR gene mutations cooccurred with KMT2D gene mutations. There were several differences in genomic alterations between patients with HRR gene mutations (HRR‐Mut) and without HRR mutations (HRR‐WT). The results revealed that TP53 and RB1 were commonly mutated genes in both groups. Mutations in the KMT2D gene and genes in the RTK‐RAS pathway occurred more frequently in the HRR‐Mut group. Furthermore, we found that mutations in HRR genes were associated with high TMB (Wilcoxon, p = 0.048), but there was no correlation of HRR gene mutation status with PD‐L1 expression. Conclusions We exhaustively describe the genomic alteration profile of Chinese SCLC patients and provide further evidence that HRR gene mutations are prevalent in SCLC patients.

show abstract

Tumour PD-L1 Expression in Small-Cell Lung Cancer: A Systematic Review and Meta-Analysis

Cited by 47 publications

References 90 publications

The clinical impact of three validated PD-L1 immunohistochemistry assays as a prognostic factor in small cell lung cancer

The clinical impact of three validated PD-L1 immunohistochemistry assays as a prognostic factor in small cell lung cancer

A narrative review of current and potential prognostic biomarkers for immunotherapy in small-cell lung cancer

Mutational landscape of homologous recombination‐related genes in small‐cell lung cancer

Contact Info

Product

Resources

About