Problems of variable biomarker evaluation in stratified medicine research—A case study of ERCC1 in non-small-cell lung cancer

Malottki, K; Popat, Sanjay; Deeks, Jonathan J; Riley, Richard D; Nicholson, Andrew G.; Billingham, Lucinda

doi:10.1016/j.lungcan.2015.11.017

Cited by 11 publications

(6 citation statements)

References 17 publications

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“…Although it is possible that immunotherapy will be used in some NSCLC patients (West, 2014), it is most likely that traditional chemotherapy still remains a viable option for many patients with advanced disease. Currently, none of the studied biomarkers for cytotoxic therapy is employed in broad clinical practice for reasons ranging from insufficient clinical validation, to large variations in evaluation procedures and heterogeneity of the tumours, to the principal limitations of single-molecule measurements as biomarkers of complex biological processes (Malottki et al , 2016; Souglakos, 2015; Toffart et al , 2014). …”

Section: Discussionmentioning

confidence: 99%

Serum proteomic test in advanced non-squamous non-small cell lung cancer treated in first line with standard chemotherapy

et al. 2016

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Background:VeriStrat is a blood-based proteomic test with predictive and prognostic significance in second-line treatments for non-small cell lung cancer (NSCLC). This trial was designed to investigate the role of VeriStrat in first-line treatment of advanced NSCLC with standard chemotherapy. Here we present the results for 76 non-squamous patients treated with a combination of carboplatin or cisplatin with pemetrexed.Methods:The test-assigned classifications of VeriStrat Good or VeriStrat Poor to samples collected at baseline. The primary end point was progression-free survival (PFS); secondary end points included overall survival (OS) and objective response. Exploratory analyses of end points separately in carboplatin/pemetrexed and cisplatin/pemetrexed subgroups were also conducted.Results:Patients classified as VeriStrat Good had longer PFS and OS than VeriStrat Poor: 6.5 vs 1.6 months and 10.8 vs 3.4 months, respectively; the corresponding hazard ratios (HRs) were 0.36 (P<0.0001) and 0.26 (P<0.0001); they were also more likely to achieve objective response. Prognostic significance of VeriStrat was confirmed in multivariate analysis. Significant differences in OS and PFS between Veristrat classifications were also found when treatment subgroups were analysed separately.Conclusions:The trial demonstrated clinical utility of VeriStrat as a prognostic test for standard first-line chemotherapy of non-squamous advanced NSCLC.

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Section: Discussionmentioning

confidence: 99%

Serum proteomic test in advanced non-squamous non-small cell lung cancer treated in first line with standard chemotherapy

et al. 2016

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“…While efforts are made by the implementation of Good Laboratory Practice to uphold the quality of management controls to ensure consistent and reliability of results, there are other sources of variation for the same biomarker. The variations in evaluating the same target protein, epigenetic change or gene expression makes it different to compare studies due to the lack of standardization of methodology91 . NGS performed in 5 different centers of the…”

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confidence: 99%

Novel urinary biomarkers for the detection of bladder cancer: A systematic review

Tan

et al. 2018

Cancer Treatment Reviews

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“…Therefore, identifying the molecular biomarkers of platinum resistance to not only screen chemo sensitive patients, but also to select a suitable drug with minimum toxicities synthesized with a cost-effective approach is the need of the hour. This will directly improve patient outcome 5 . There is a scarcity for clinical biomarkers to customize chemo sensitivity.…”

Section: Introductionmentioning

confidence: 99%

ERCC1_202 Is A Prognostic Biomarker in Advanced Stage Non-Small Cell Lung Cancer Patients Treated with Platinum-Based Chemotherapy

et al. 2017

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Purpose: To develop a qPCR method to examine the 202 isoform of excision repair cross-complementation group 1 (ERCC1_202) and to evaluate its clinical utility as a predictive biomarker for platinum-based chemotherapy in non-small cell lung cancer (NSCLC).Methods: The relative complementary DNA (cDNA) quantification for ERCC1_202 was conducted using a fluorescence-based, real-time detection method and β-actin was used as a reference gene.Results: A strong correlation was observed between ERCC1_202 mRNA and ERCC1 mRNA levels in NSCLC cells (P < 0.001). 28 patients completed this research. Our results implied that as ERCC1_202 levels increased, the risk of progression (HR = 4.296, P = 0.011) and death (HR = 6.503, P = 0.001) increased. At multivariate analysis, high expression of ERCC1_202 was shown to be an independent predictive factor for time to progression (P = 0.047), and progression-free survival (P = 0.014). However, the high expression of ERCC1_202 was not an independent predictive factor for response (P = 0.324).Conclusions: This study suggests that the efficacy of platinum-based chemotherapy can be improved when customized according to the expression of ERCC1_202.

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Problems of variable biomarker evaluation in stratified medicine research—A case study of ERCC1 in non-small-cell lung cancer

Cited by 11 publications

References 17 publications

Serum proteomic test in advanced non-squamous non-small cell lung cancer treated in first line with standard chemotherapy

Serum proteomic test in advanced non-squamous non-small cell lung cancer treated in first line with standard chemotherapy

Novel urinary biomarkers for the detection of bladder cancer: A systematic review

ERCC1_202 Is A Prognostic Biomarker in Advanced Stage Non-Small Cell Lung Cancer Patients Treated with Platinum-Based Chemotherapy

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