scholarly journals Definition of a new blood cell count (BCT) score for early survival prediction for non-small cell lung cancer patients treated with atezolizumab: Integrated analysis of 4 multicenter clinical trials

2021 ◽  
Author(s):  
jianguo Zhou ◽  
Ada Hang-Heng Wong ◽  
haitao wang ◽  
Su-han Jin ◽  
Fangya Tan ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Clinical Trials ◽  
Treatment Cycle ◽  
Single Agent ◽  
Predictive Biomarkers ◽  
Small Cell ◽  
Blood Cell Count ◽  
Small Cell Lung ◽  
Nsclc Patients ◽  
Agent Treatment

Introduction Immune checkpoint inhibitor (ICI) therapy is a major breakthrough in non-small cell lung cancer (NSCLC) treatment. However, valid predictive biomarkers are lacking. Blood cell count test (BCT) provides a direct quantification of various types of immune cells (ICs) to reveal the immune landscape to predict ICI treatment. Methods This study analyzed four international, multi-center clinical trials (OAK, BIRCH, POPLAR and FIR trials) to conduct post-hoc analyses of NSCLC patients undergoing atezolizumab (anti-PD-L1) single-agent treatment (n = 1,479) or docetaxel single-agent treatment (n = 707). BCT was conducted at three timepoints: pre-treatment (T1), the first day of treatment cycle 3 (T2), and first day of treatment cycle 5 (T3). Univariate and multivariate Cox regression analyses were conducted to identify early BCT biomarkers to predict atezolizumab treatment outcomes in NSCLC patients. Results The BCT biomarkers of neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) at timepoint T3 and neutrophil-to-monocyte ratio (NMR) at timepoint T2 were identified as strong predictive biomarkers for atezolizumab (Ate)-treated NSCLC patients in comparison to docetaxel (Dtx)-treated patients regarding overall survival (OS) (BCTscore low-risk: HR Ate vs Dtx = 1.54 (95% CI: 1.04-2.27), P = 0.036; high-risk: HR Ate vs Dtx = 0.84 (95% CI: 0.62-1.12), P = 0.236). This identified BCTscore model showed better OS AUC in the OAK (AUC12month=0.696), BIRCH (AUC12month=0.672) and POPLAR+FIR studies (AUC12month=0.727) than that of each of the three single BCT biomarkers. Conclusion The BCTscore model is a valid predictive and prognostic biomarker for atezolizumab-treated NSCLC patients.

scholarly journals 329 Early blood cell count test (BCT) for survival prediction for non-small cell lung cancer patients treated with atezolizumab: integrated analysis of 4 multicenter clinical trials

2021 ◽  
Vol 9 (Suppl 3) ◽  
pp. A355-A355
Author(s):  
Jian-Guo Zhou ◽  
Ada Hang-Heng Wong ◽  
Haitao Wang ◽  
Su-Han Jin ◽  
Fangya Tan ◽  
...  
Keyword(s):  
Single Agent ◽  
Predictive Biomarkers ◽  
Predictive Biomarker ◽  
Small Cell ◽  
Blood Cell Count ◽  
Small Cell Lung ◽  
Link Type ◽  
Pre Treatment ◽  
Nsclc Patients ◽  
Agent Treatment

BackgroundImmune checkpoint inhibitor (ICI) therapy is a major breakthrough for non-small cell lung cancer (NSCLC) treatment given its high efficacy and tolerable toxicity. Although pre-treatment PD-L1 expression levels and tumor mutation burden (TMB) may serve as prognostic biomarkers for patient stratification, effective predictive biomarkers are lacking. Blood cell count test (BCT) is a routine, regular blood test conducted before and during treatment to provide a direct overview of the immune landscape based on the counts of various types of immune cells (ICs). For instance, previous studies showed that neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) both indicate poor treatment outcomes of ICI therapy of NSCLC patients.MethodsThis study analyzed relevant combinations of IC counts from four international, multi-center clinical trials of OAK, BIRCH, POPLAR and FIR to conduct post-hoc analysis of NSCLC patients undergoing atezolizumab (anti-PD-L1) single-agent treatment (n = 1,479), while docetaxel single-agent treatment (n = 707) was used as control. BCT was conducted at three timepoints, T1 to T3, during pre-treatment and on the first day of treatment cycles 3 and 5, which correspond to baseline, 6, and 12 weeks on-treatment, respectively. Univariate and multivariate Cox regression analysis was conducted to identify NLR_T3, PLR_T3 and neutrophil-to-monocyte (NMR) at T2 as early BCT biomarkers that may predict ICI efficacy. Next, univariate and multivariate Cox proportional hazards regression analysis were used to identify any effective combination of BCT biomarkers and their absolute cutoff values that may serve as predictive biomarkers to predict atezolizumab treatment outcomes. Lastly, combinations of these BCT biomarkers were tested to optimize BCTscore model for clinical evaluation.ResultsThe final BCT biomarker combination, comprising of the BCT biomarkers of NLR and PLR at 12 weeks on-treatment (T3) and NMR at 6 weeks on-treatment (T2), was identified to be a strong predictive biomarker for atezolizumab (Ate)-treated NSCLC patients in comparison to docetaxel (Dtx)-treated patients regarding overall survival (OS) (BCTscore low-risk: HR Ate vs Dtx = 1.54 (95% CI: 1.04–2.27), P = 0.036; high-risk: HR Ate vs Dtx = 0.84 (95% CI: 0.62–1.12), P = 0.236). Our BCTscore model consistently exhibited better OS AUC in the OAK (AUC12month=0.696), BIRCH (AUC12month=0.672) and POPLAR+FIR studies (AUC12month=0.727) than that of each of the three BCT biomarkers in these three studies.ConclusionsThe BCTscore of NLR at 12 weeks, PLR at 12 weeks and NMR at 6 weeks is a strong efficacy predictive biomarker for atezolizumab-treated NSCLC patients.AcknowledgementsThe authors declare no conflict of interest. This publication is based on research using data from Genentech, Inc. (one of subsidiaries of Roche Group) that has been made available through Vivli, Inc (Data Request ID: 5935; Lead Investigator: Dr. Jian-Guo Zhou). Vivli has not contributed to or approved, and is not in any way responsible for, the contents of this publication.Trial RegistrationDeidentified individual participant data from the single-arm phase II studies of FIR study (NCT01846416; as of Janurary 7, 2015) [Spigel2018] and BIRCH (NCT02031458; as of May 28, 2015) [Peters2017], and the two-arm randomized controlled trials (RCT) of the POPLAR phase II study (NCT01903993; as of May 8, 2015) [Fehrenbacher2016] and the OAK phase III study (NCT02008227; as of July 7, 2016) [Rittmeyer2017] were made available by Genentech Inc. and accessed through the secure Vivli online platform.Ethics ApprovalBoth studies were approved by the respective national ethics committees and institutional review boards and written informed consent was obtained from all patients.

scholarly journals Vinorelbine in Non-Small Cell Lung Cancer: Real-World Data From a Single-Institution Experience

2020 ◽  
Vol 28 (3) ◽  
pp. 237-248
Author(s):  
Stefania Nobili ◽  
Daniele Lavacchi ◽  
Gabriele Perrone ◽  
Giulio Vicini ◽  
Renato Tassi ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Real World ◽  
Single Agent ◽  
Small Cell ◽  
Small Cell Lung ◽  
Single Institution ◽  
Nsclc Patients ◽  
Combination Regimens

The use of vinorelbine as a single agent or in combination regimens in non-small cell lung cancer (NSCLC) is associated with satisfactory clinical activity. However, the role of vinorelbine-based chemotherapy in chemonaive locally advanced unresectable or metastatic NSCLC patients, according to real-world treatment patterns, has still not been widely explored. Eighty-one patients treated at a single institution were retrospectively analyzed. Thirty-seven received standard first-line single-agent vinorelbine, and 44 received vinorelbine plus platinum drugs, based on physician’s choice; 61.7% were older than 70 years, and 60.5% were affected by ≥2 comorbidities. Sixty-three patients were evaluable for objective response: 22% achieved partial response and 41% stable disease. Median progression-free survival (PFS) was 5.4 months. A benefit in PFS was observed in patients treated with combinations vs. single-agent vinorelbine (6.7 vs. 3.5 months, p = 0.043). Median overall survival (OS) was 10.4 months without a statistically significant difference between treatments (12.4 vs. 7.5 months). In 55 stage IV patients, OS was positively correlated with combination regimens, M1a stage, or ≤2 metastatic lesions. Grade 3‐4 toxicity occurred in 33% of patients, and dose reduction in 11%. A statistically significant higher incidence of toxicity was observed in patients receiving combinations, in women, in patients younger than 75 years, or patients with metastases. In this real-word analysis, we confirmed the efficacy and tolerability of vinorelbine as a single agent or combined with platinums in patients usually underrepresented in controlled clinical trials. Single-agent vinorelbine may represent a suitable option in elderly or unfit NSCLC patients and warrants investigation as a potential drug candidate for immunochemotherapy combination regimens.

scholarly journals First-line single agent treatment with gefitinib in patients with advanced non-small-cell lung cancer

2010 ◽  
Vol 29 (1) ◽  
pp. 126 ◽  
Author(s):  
Yong-Mei Yin ◽  
Yi-Ting Geng ◽  
Yong-Feng Shao ◽  
Xiao-Li Hu ◽  
Wei Li ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Single Agent ◽  
Small Cell ◽  
Small Cell Lung ◽  
First Line ◽  
Agent Treatment

scholarly journals Efficacy and toxicities of combination maintenance therapy in the treatment of advanced non-small-cell lung cancer: an up-to-date meta-analysis

2019 ◽  
Vol 39 (6) ◽  
Author(s):  
Jianming Hu ◽  
Jiawei Hu ◽  
Xiaolan Liu ◽  
Long Li ◽  
Xue Bai
Keyword(s):  
Lung Cancer ◽  
Maintenance Therapy ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Advanced Nsclc ◽  
Single Agent ◽  
Small Cell ◽  
Small Cell Lung ◽  
Grade 3 ◽  
Nsclc Patients

Abstract Background: Single agent maintenance therapy has been approved for the treatment of advanced non-small-cell lung cancer (NSCLC) due to its potential survival benefits, but whether combined maintenance therapy would improve the survival of advanced NSCLC remains undetermined. Methods: Relevant trials were identified by searching electronic databases and conference meetings. Prospective randomized controlled trials (RCTs) assessing combination maintenance therapy in advanced NSCLC patients were included. Outcomes of interest included overall survival (OS), progression-free survival (PFS), and grade 3–4 toxicities. Results: A total of 1950 advanced NSCLC patients received combination maintenance treatment from six trials were included for analysis. The use of doublet maintenance therapy in NSCLC patients significantly improved PFS (HR 0.74, 95%CI: 0.59–0.93, P = 0.010), but not for OS (HR 0.95, 95%CI: 0.85–1.07, P = 0.40) in comparison with single agent maintenance therapy. Similar results were observed in sub-group analysis according to treatment regimens. In addition, there was no significantly risk difference between doublet and single agent maintenance therapy in terms of grade 3/4 hematologic and non-hematologic toxicities. Conclusion: The findings of the present study show that doublet combination maintenance therapy is superior to single agent maintenance therapy in terms of PFS, without increased grade 3–4 toxicities. Future prospective studies are recommended to clearly assess the long-term clinical benefit of doublet maintenance therapy and its impact on health-related quality of life.

scholarly journals First line Immunotherapy for Non-Small Cell Lung Cancer

2020 ◽  
Vol 13 (11) ◽  
pp. 373
Author(s):  
Nicola J. Nasser ◽  
Miguel Gorenberg ◽  
Abed Agbarya
Keyword(s):  
Lung Cancer ◽  
Clinical Trials ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Single Agent ◽  
Small Cell ◽  
Small Cell Lung ◽  
First Line ◽  
Phase 3 ◽  
Programmed Death

Immunotherapy for non-small cell lung cancer (NSCLC) is incorporated increasingly in first line treatments protocols. Multiple phase 3 studies have tested different medications targeting programmed death receptor 1 (PD-1), programmed death-ligand 1 (PD-L1), cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), with or without chemotherapy. The inclusion criteria differ between the various clinical trials, including the cut-off levels of PD-L1 expression on tumor cells, and the tumor histology (squamous or non-squamous). Patients with tumor expression levels of PD-L1 ≥ 50% are candidates for treatment with single agent Pembrolizumab or Atezolizumab. Patients with PD-L1 < 50% are candidates for immunotherapy with pembrolizumab as a single agent if PL-1 > 1%; immunotherapy doublet, Nivolumab and Ipilimumab, or single agent immunotherapy combined with chemotherapy. Here we review phase 3 clinical trials utilizing immunotherapy in the first line for treatment of NSCLC, including Pembrolizumab in KEYNOTE-024, KEYNOTE-042, KEYNOTE-189 and KEYNOTE-407; Nivolumab and Ipilimumab in CHECKMATE-227 and CHECKMATE 9LA; and Atezolizumab in IMpower110, IMpower130 and IMpower150.

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