Immunotherapy combined with chemotherapy versus chemotherapy alone as the first‐line treatment of <scp>PD‐L1</scp>‐negative and driver‐gene‐negative advanced nonsquamous non‐small‐cell lung cancer: An updated systematic review and meta‐analysis

Chai, Yun; Wu, Xinyu; Zou, Yifeng; Zhang, Xue; Bai, Hua; Dong, Mei; Duan, Jianchun

doi:10.1111/1759-7714.14664

Cited by 6 publications

(4 citation statements)

References 38 publications

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“…PD-L1 is a relatively popular biomarker at present. A meta-analysis of seven trials involving 1,132 patients with PD-L1 negative and driver gene negative advanced non squamous NSCLC showed that compared to chemotherapy alone, immunotherapy combined with chemotherapy as a first-line treatment for patients with PD-L1 negative advanced non squamous NSCLC achieved better ORR (odds ratio 2.81, 95% CI: 1.69–4.65), PFS (HR 0.63, 95% CI: 0.55–0.74, P<0.001) and OS (HR 0.68, 95% CI: 0.56–0.82, P<0.001) ( 78 ). In addition, nearly half of the NSCLC population has PD-L1-negative expression, and thus we need to understand how to choose immunotherapy for these PD-L1-negative patients.…”

Section: Discussionmentioning

confidence: 99%

Immunotherapy for advanced non-small cell lung cancer with negative programmed death-ligand 1 expression: a literature review

Bai,

Yang,

Käsmann

et al. 2024

Transl Lung Cancer Res

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Background and Objective Lung cancer, mainly non-small cell lung cancer (NSCLC), is a serious threat to human life. In particular, the prognosis for advanced patients is poor, with the 5-year survival rate being exceedingly low. In recent years, immune checkpoint inhibition has changed the pattern of the treatment of a variety of cancers, including lung cancer; however, not all patients can benefit from immunotherapy, and thus finding the right biomarkers is particularly important for guiding precise treatment. Programmed death-ligand 1 (PD-L1) expression is one of the most valuable biomarkers for predicting the efficacy of lung cancer immunotherapy. Several studies have confirmed that patients with high PD-L1 expression are more likely to benefit from immunotherapy, but there is a high proportion of people with negative PD-L1 expression constituting a patient population that cannot be ignored. This article reviews the distribution of PD-L1 expression, the methods for evaluating PD-L1, and the effectiveness of immunotherapy for advanced NSCLC with negative PD-L1 expression. Methods We performed a literature review to identify relevant data published until September 2022. In order to organize related information, we searched for literature in PubMed; abstracts and reports published in the American Society of Clinical Oncology (ASCO), the European Society for Medical Oncology (ESMO), the World Conference on Lung Cancer (WCLC), and other congresses; and clinical trial information registered on ClinicalTrials.gov. Information on the distribution of PD-L1 expression, detection of PD-L1, and immunotherapy efficacy for NSCLC with negative PD-L1 expression was collated and reviewed. Key Content and Findings The incidence of PD-L1 expression in patients with stage IIIB/IV NSCLC is similar in all regions of the world, but PD-L1 expression level is associated with certain clinicopathological features. The expression of PD-L1 can be evaluated by various detecting methods. Some immunotherapy regimens have better efficacy than traditional chemotherapy in patients with negative PD-L1 expression. Conclusions Patients with NSCLC and negative PD-L1 expression can receive better survival benefits under some immunotherapy types, and these may represent a better treatment option for this relatively small patient population.

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Section: Discussionmentioning

confidence: 99%

Immunotherapy for advanced non-small cell lung cancer with negative programmed death-ligand 1 expression: a literature review

Bai,

Yang,

Käsmann

et al. 2024

Transl Lung Cancer Res

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“…The original contributions presented in the study are included in the article/Additional files 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20. Further inquiries can be directed to the corresponding authors. The Additional files 1,2,3,4,5,6,7,8,9,10,11,12,13,14,15,16,17,18,19,20 for this article can be found online.…”

Section: Supplementary Informationmentioning

confidence: 99%

“…molecules whose purpose is to block checkpoints and activate T-cell-based immunotherapy [6]. For patients with advanced NSCLC with tumor proportional score(TPS) of PD-L1 ≥ 1%, immune monotherapy can significantly improve the progression-free survival (PFS) and overall survival (OS) of patients compared with chemotherapy, especially for patients with TPS ≥ 50%, while immunotherapy combined with chemotherapy significantly prolonged PFS and OS of patients with PD-L1 negative and driver-gene-negative advanced non-squamous NSCLC [7][8][9][10]. Positive responses to immunotherapy often rely on the interaction of tumor cells with immune regulation within the TME.…”

Section: Introductionmentioning

confidence: 99%

Genomic and immunogenomic analysis of three prognostic signature genes in LUAD

et al. 2023

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Background Searching for immunotherapy-related markers is an important research content to screen for target populations suitable for immunotherapy. Prognosis-related genes in early stage lung cancer may also affect the tumor immune microenvironment, which in turn affects immunotherapy. Results We analyzed the differential genes affecting lung cancer patients receiving immunotherapy through the Cancer Treatment Response gene signature DataBase (CTR-DB), and set a threshold to obtain a total of 176 differential genes between response and non-response to immunotherapy. Functional enrichment analysis found that these differential genes were mainly involved in immune regulation-related pathways. The early-stage lung adenocarcinoma (LUAD) prognostic model was constructed through the cancer genome atlas (TCGA) database, and three target genes (MMP12, NFE2, HOXC8) were screened to calculate the risk score of early-stage LUAD. The receiver operating characteristic (ROC) curve indicated that the model had good prognostic value, and the validation set (GSE50081, GSE11969 and GSE42127) from the gene expression omnibus (GEO) analysis indicated that the model had good stability, and the risk score was correlated with immune infiltrations to varying degrees. Multi-type survival analysis and immune infiltration analysis revealed that the transcriptome, methylation and the copy number variation (CNV) levels of the three genes were correlated with patient prognosis and some tumor microenvironment (TME) components. Drug sensitivity analysis found that the three genes may affect some anti-tumor drugs. The mRNA expression of immune checkpoint-related genes showed significant differences between the high and low group of the three genes, and there may be a mutual regulatory network between immune checkpoint-related genes and target genes. Tumor immune dysfunction and exclusion (TIDE) analysis found that three genes were associated with immunotherapy response and maybe the potential predictors to immunotherapy, consistent with the CTR-DB database analysis. Conclusions From the perspective of data mining, this study suggests that MMP12, NFE2, and HOXC8 may be involved in tumor immune regulation and affect immunotherapy. They are expected to become markers of immunotherapy and are worthy of further experimental research.

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“…With immune escape mechanisms under investigation, gold treatment guidelines for advanced driver genenegative NSCLC patients in China incorporated immune checkpoint inhibitor (ICI) monotherapy, including programmed cell death protein 1/programmed cell deathligand 1 inhibitor monotherapy, and ICIs plus platinumbased doublet chemotherapy (5). In most clinical trials (6)(7)(8)(9), such as keynote 024, checkmate 227 et al, the survival rate of advanced NSCLC improves dramatically as a result of immunotherapy.…”

Section: Introductionmentioning

confidence: 99%

Immune checkpoint inhibitors beyond first-line progression with prior immunotherapy in patients with advanced non-small cell lung cancer

Xu¹,

Hao²,

Zeng³

et al. 2023

J Thorac Dis

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Background: Immunotherapy, monotherapy, and immunotherapy plus platinum-based chemotherapy are the standard treatments for advanced non-small cell lung cancer (NSCLC) patients with negative driver genes. However, the impact of similar continuing immunotherapy beyond progression (IBP) of first-line immunotherapy for advanced NSCLC has not yet been shown. This study aimed to estimate the impact of immunotherapy beyond first-line progression (IBF) and evaluate the factors associated with second-line efficacity.Methods: Ninety-four cases of advanced NSCLC patients with progressive disease (PD) post firstline treatment with platinum-based chemotherapy plus immunotherapy and administrated prior immune checkpoint inhibitors (ICIs) between November 2017 and July 2021 were retrospectively analyzed. Survival curves were plotted using the Kaplan-Meier method. Cox proportional hazards regression analyses were applied to determine predictive factors independently associated with second-line efficacity.Results: A total of 94 patients were incorporated in this study. Patients who continued the original ICIs after initial PD were defined as IBF (n=42), whereas those who discontinued immunotherapy were defined as non-IBF (n=52). The second-line objective response rates (ORR, ORR = CR + PR) of patients in the IBF and non-IBF groups were 13.5% vs. 28.6%, respectively (P=0.070). No significant survival difference was found between patients in the IBF and non-IBF groups in first-line median progression-free survival (PFS) (mPFS1, 6.2 vs. 5.1 m, P=0.490), second-line median PFS (mPFS2, 4.5 vs. 2.6 m, P=0.216), or median overall survival (OS) (mOS, 14.4 vs. 8.3 m, P=0.188). However, the benefits inPFS2 were observed in individuals performed PFS1 >6 months (group A) than those of PFS1 ≤6 months (group B) (median PFS2, 4.6 vs. 3.2 m, P=0.038). Multivariate analyses did not reveal any independent prognostic factors for efficacy. Conclusions:The benefits of continuing prior ICIs administration beyond first-line immunotherapy progression might not be obvious in patients with advanced NSCLC, but those first line treatment showed a longer period may receive efficacy benefits.

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Immunotherapy combined with chemotherapy versus chemotherapy alone as the first‐line treatment of PD‐L1‐negative and driver‐gene‐negative advanced nonsquamous non‐small‐cell lung cancer: An updated systematic review and meta‐analysis

Cited by 6 publications

References 38 publications

Immunotherapy for advanced non-small cell lung cancer with negative programmed death-ligand 1 expression: a literature review

Immunotherapy for advanced non-small cell lung cancer with negative programmed death-ligand 1 expression: a literature review

Genomic and immunogenomic analysis of three prognostic signature genes in LUAD

Immune checkpoint inhibitors beyond first-line progression with prior immunotherapy in patients with advanced non-small cell lung cancer

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