Dataset Information

Integrating Circulating Biomarkers in the Immune Checkpoint Inhibitor Treatment in Lung Cancer.

ABSTRACT: Immune checkpoint inhibitors are now a cornerstone of treatment for non-small cell lung cancer (NSCLC). Tissue-based assays, such as Programmed cell death protein 1 (PD-L1) expression or mismatch repair deficiency/microsatellite instability (MMRD/MSI) status, are approved as treatment drivers in various settings, and represent the main field of research in biomarkers for immunotherapy. Nonetheless, responses have been observed in patients with negative PD-L1 or low tumor mutational burden. Some aspects of biomarker use remain poorly understood and sub-optimal, in particular tumoral heterogeneity, time-evolving sampling, and the ability to detect patients who are unlikely to respond. Moreover, tumor biopsies offer little insight into the host's immune status. Circulating biomarkers offer an alternative non-invasive solution to address these pitfalls. Here, we summarize current knowledge on circulating biomarkers while using liquid biopsies in patients with lung cancer who receive treatment with immune checkpoint inhibitors, in terms of their potential as being predictive of outcome as well as their role in monitoring ongoing treatment. We address host biomarkers, notably circulating immune cells and soluble systemic immune and inflammatory markers, and also review tumor markers, including blood-based tumor mutational burden, circulating tumor cells, and circulating tumor DNA. Technical requirements are discussed along with the current limitations that are associated with these promising biomarkers.

SUBMITTER: Duchemann B

PROVIDER: S-EPMC7761725 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature

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Integrating Circulating Biomarkers in the Immune Checkpoint Inhibitor Treatment in Lung Cancer.

Duchemann Boris B Remon Jordi J Naigeon Marie M Mezquita Laura L Ferrara Roberto R Cassard Lydie L Jouniaux Jean Mehdi JM Boselli Lisa L Grivel Jonathan J Auclin Edouard E Desnoyer Aude A Besse Benjamin B Chaput Nathalie N

Cancers 20201203 12

Immune checkpoint inhibitors are now a cornerstone of treatment for non-small cell lung cancer (NSCLC). Tissue-based assays, such as Programmed cell death protein 1 (PD-L1) expression or mismatch repair deficiency/microsatellite instability (MMRD/MSI) status, are approved as treatment drivers in various settings, and represent the main field of research in biomarkers for immunotherapy. Nonetheless, responses have been observed in patients with negative PD-L1 or low tumor mutational burden. Some ...[more]

PMID: 33287347

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Project description:ObjectivesBased on the acknowledged organ-specific immune microenvironment, little is known regarding the efficacy of immunotherapy in patients with lung cancer according to metastatic sites. This meta-analysis aimed to explore the efficacy of immune checkpoint inhibitors (ICIs) vs chemotherapy in patients with lung cancer with liver metastases (LM) or brain metastases (BM).DesignMeta-analysis and systematic review.Data sourcesWe systematically searched in electronic databases (PubMed, EMBASE, Cochrane Library and Web of Science), up to 31 January 2022. We also reviewed the abstracts from major international conferences. Eligibility criteria were randomised controlled phase II or III trials reporting the overall survival (OS) or progression-free survival (PFS) of LM or BM subsets.Data extraction and synthesisHazard ratios (HRs) with 95% CIs for OS and PFS were extracted and aggregated using a random-effects model.ResultsTwenty-four randomised controlled trials with available outcomes for patients with BMs or LMs were identified. A total of 1124 patients with BM and 2077 patients with LM were included in the analysis. The pooled OS HR of patients with LMs was 0.83 (95% CI 0.72 to 0.95), and that of patients without LM 0.73 (95% CI 0.69 to 0.79). LM was associated with less benefits from ICIs. In patients with BM treated with ICIs, the pooled OS HR compared with the control arms was 0.71 (95% CI 0.53 to 0.94). Subgroup analyses by histology suggested that only patients with non-small cell lung cancer (NSCLC) with BM could gain benefit from ICIs (HR 0.53, 95% CI 0.41 to 0.68). BM negatively influenced efficacy of immunotherapy in patients with small cell lung cancer.ConclusionsOur results showed immunotherapy demonstrated efficacy in patients with lung cancer with LM and BM, survival benefits dominantly favoured patients with NSCLC. Patients with lung cancer with LM obtained less benefits from ICIs than those without. Therefore, organ-specific immunotherapeutic approaches should be considered.Prospero registration numberCRD42020212797.

Project description:BackgroundThe advent of immune checkpoint inhibitors (ICIs) therapy has resulted in significant survival benefits in patients with non-small-cell lung cancer (NSCLC) without increasing toxicity. However, the utilisation of immunotherapy for small-cell lung cancer (SCLC) remains unclear, with a scarcity of systematic comparisons of therapeutic effects and safety of immunotherapy in these two major lung cancer subtypes. Herein, we aimed to provide a comprehensive landscape of immunotherapy and systematically review its specific efficacy and safety in advanced lung cancer, accounting for histological types.MethodsWe identified studies assessing immunotherapy for lung cancer with predefined endpoints, including overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and treatment-related adverse events (TRAE), from PubMed, Embase, Medline, and Cochrane library. A random-effects or fixed-effect model was adopted according to different settings.ResultsOverall, 38 trials with 20,173 patients with lung cancer were included in this study. ICI therapy resulted in a significantly prolonged survival in both patients with NSCLC and SCLC when compared with chemotherapy (hazard ratio [HR] = 0.74; 95% confidence interval [CI], 0.70-0.79] and [HR = 0.82; 95% CI, 0.75-0.90], respectively). The magnitude of disease control and survival benefits appeared superior with ICI plus standard of care (SOC) when compared with SOC alone. OS and PFS advantages were observed only when immunotherapy was employed as the first-line treatment in patients with SCLC.ConclusionICI therapy is a promising therapeutic option in patients with NSCLC and SCLC. ICI plus SOC can be recommended as the optimal first-line treatment for patients with SCLC, and double-target ICIs combined with SOC are recommended in patients with NSCLC as both the first and subsequent lines of treatment. Additionally, non-first-line immunotherapy is not recommended in patients with SCLC.

Dataset Information

Integrating Circulating Biomarkers in the Immune Checkpoint Inhibitor Treatment in Lung Cancer.

Publications

Integrating Circulating Biomarkers in the Immune Checkpoint Inhibitor Treatment in Lung Cancer.

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