Dataset Information

Circulating tumor cells in advanced non-small cell lung cancer patients are associated with worse tumor response to checkpoint inhibitors.

ABSTRACT:

Background

Non-small cell lung cancer (NSCLC) patients treated with checkpoint inhibitors show long lasting responses, but it is hard to predict which patients will profit from this treatment with the currently used marker, programmed death ligand 1 (PD-L1). We hypothesized that circulating tumor cells (CTC) or tumor derived extracellular vesicles (tdEV) are markers of treatment efficacy.

Methods

Patients with advanced NSCLC treated with checkpoint inhibitors were included. Blood was drawn at baseline (T0) and at 4?weeks of treatment (T1) for analysis of CTC and tdEV using CellSearch®. Tumor response was classified as partial or complete response based on the response evaluation criteria in solid tumors (RECISTv1.1) measured 4-6?weeks after start of treatment. Durable response was defined as stable disease, partial or complete response without disease progression at 6?months. Analyses were adjusted for covariables including PD-L1 expression.

Results

We included 104 patients (30 with a tumor response, 74 non-responders, 2 responses not evaluable due to early death); 63 patients provided T1 samples. All patients were treated with PD-L1 inhibitors. The majority of patients received second (85%) or third line (treatment with nivolumab monotherapy (89%). CTC were present in 33/104 patients at T0 (32%) and 17/63 at T1 (27%), 9/63 patients had CTC (14%) at both time points. The presence of CTC, both at T0 (OR?=?0.28, p?=?0.02,) and T1 (OR?=?0.07, p?ConclusionCTC occur in one third of advanced NSCLC patients and their presence is a predictive factor for a worse durable response rate to checkpoint inhibitors. tdEV are associated with shorter survival but not with response.

SUBMITTER: Tamminga M

PROVIDER: S-EPMC6617698 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature

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Publications

Circulating tumor cells in advanced non-small cell lung cancer patients are associated with worse tumor response to checkpoint inhibitors.

Tamminga Menno M de Wit Sanne S Hiltermann T Jeroen N TJN Timens Wim W Schuuring Ed E Terstappen Leon W M M LWMM Groen Harry J M HJM

Journal for immunotherapy of cancer 20190710 1

<h4>Background</h4>Non-small cell lung cancer (NSCLC) patients treated with checkpoint inhibitors show long lasting responses, but it is hard to predict which patients will profit from this treatment with the currently used marker, programmed death ligand 1 (PD-L1). We hypothesized that circulating tumor cells (CTC) or tumor derived extracellular vesicles (tdEV) are markers of treatment efficacy.<h4>Methods</h4>Patients with advanced NSCLC treated with checkpoint inhibitors were included. Blood ...[more]

PMID: 31291995

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Project description:IntroductionRecent clinical trials have confirmed that anti-programmed cell death-1/ligand 1 (anti-PD-1/L1) combined with either anti-cytotoxic T-lymphocyte-associated protein 4 (anti-CTLA-4) or anti-T-cell immunoreceptor with Ig and ITIM domains (TIGIT) antibodies (dual immunotherapy) produced significant benefits as first-line therapies for patients with advanced non-small cell lung cancer (NSCLC). However, it also increased the incidence of adverse reactions, which cannot be ignored. Our study aims to explore the efficacy and safety of dual immunotherapies in advanced NSCLC.MethodsThis meta-analysis ultimately included nine first-line randomized controlled trials collected from PubMed, EMBASE, and Cochrane Central Register of Controlled Trials databases until 13 August 2022. Efficacy was measured as the hazard ratio (HR) and 95% confidence interval (CI) for progression-free survival (PFS), overall survival (OS), and risk ratio (RR) for the objective response rates (ORRs). Treatment safety was assessed by RR of any grade of treatment-related adverse events (TRAEs) and grade ≥ 3 TRAEs.ResultsOur results demonstrated that, compared to chemotherapy, dual immunotherapy shows durable benefits in OS (HR = 0.76, 95% CI: 0.69-0.82) and PFS (HR = 0.75, 95% CI: 0.67-0.83) across all levels of PD-L1 expression. Subgroup analysis also presented that dual immunotherapy resulted in improved long-term survival compared with chemotherapy in patients with a high tumor mutational burden (TMB) (OS: HR = 0.76, p = 0.0009; PFS: HR = 0.72, p < 0.0001) and squamous cell histology (OS: HR = 0.64, p < 0.00001; PFS: HR = 0.66, p < 0.001). However, compared with immune checkpoint inhibitor (ICI) monotherapy, dual immunotherapy shows some advantages in terms of OS and ORR and only improved PFS (HR = 0.77, p = 0.005) in PD-L1 < 25%. With regard to safety, there was no significant difference in any grade TRAEs (p = 0.05) and grade ≥ 3 TRAEs (p = 0.31) between the dual immunotherapy and chemotherapy groups. However, compared with ICI monotherapy, dual immunotherapy significantly increased the incidence of any grade TRAEs (p = 0.03) and grade ≥ 3 TRAEs (p < 0.0001).ConclusionsAs for the efficacy and safety outcome, compared with standard chemotherapy, dual immunotherapy remains an effective first-line therapy for patients with advanced NSCLC, especially for patients with high TMB levels and squamous cell histology. Furthermore, compared to single-agent immunotherapy, dual immunotherapy is only considered for use in patients with low PD-L1 expression in order to reduce the emergence of resistance to immunotherapy.Systematic Review Registation: https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42022336614.

Dataset Information

Circulating tumor cells in advanced non-small cell lung cancer patients are associated with worse tumor response to checkpoint inhibitors.

Background

Methods

Results

Publications

Circulating tumor cells in advanced non-small cell lung cancer patients are associated with worse tumor response to checkpoint inhibitors.

Similar Datasets

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