Retrospective Assessment of a Serum Proteomic Test in a Phase III Study Comparing Erlotinib plus Placebo with Erlotinib plus Tivantinib (MARQUEE) in Previously Treated Patients with Advanced Non-Small Cell Lung Cancer

Buttigliero, Consuelo; Shepherd, Frances A.; Schwartz, Brian; Орлов, С. В.; Favaretto, Adolfo; Santoro, Armando; Hirsh, Vera; Blackler, Adele; Roder, Joanna; Spigel, David R.; Novello, Silvia; Akerley, Wallace; Scagliotti, Giorgio Vittorio

doi:10.1634/theoncologist.2018-0089

Cited by 11 publications

(7 citation statements)

References 32 publications

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“…1). This is consistent with several randomised studies of pretreated patients [10], [11], [14], [16], while two other trials of second line therapy found evidence of the (negative) predictive value of VeriStrat, but all of these studies were conducted among primarily good PS patients [13], [14].…”

Section: Discussionsupporting

confidence: 89%

“…Several studies show that VeriStrat is a prognostic marker such that VSG patients have better outcomes including survival than VSP patients [9], [10], [11], [12], [13], [14], [15], [16], [17], [18], [19], [20], [21], [22], [23], [24]. However, the vast majority of the patients included in these studies had predominantly good PS (ECOG 0–1).…”

Section: Introductionmentioning

confidence: 99%

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The clinical role of VeriStrat testing in patients with advanced non–small cell lung cancer considered unfit for first-line platinum-based chemotherapy

Lee

Upadhyay

Lewanski

et al. 2019

European Journal of Cancer

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PurposeWe previously demonstrated that the median survival of patients with poor prognosis non–small cell lung cancer (NSCLC) considered unfit for first-line platinum chemotherapy was <4 months. We evaluated whether VeriStrat could be used as a prognostic or predictive biomarker in this population.Experimental designWe conducted a randomised double-blind trial among patients with untreated advanced NSCLC considered unfit for platinum chemotherapy because of poor performance status (PS) or multiple comorbidities. All patients received active supportive care (ASC) and were treated with either oral erlotinib or placebo daily. Five hundred twenty-seven patients had plasma samples for VeriStrat classification: good (VeriStrat Good [VSG]) or poor (VeriStrat Poor [VSP]). Main end-point was overall survival.ResultsFifty-five percent patients had VSG, and 83% had Eastern Cooperative Oncology Group (ECOG) 2–3 at baseline. VeriStrat was strongly associated with survival. Among patients managed with ASC only, the adjusted hazard ratio (HR) was 0.54 (p < 0.001) for VSG versus VSP. The association was consistent across patient factors: HR = 0.25 (p = 0.004) and HR = 0.56 (p < 0.001) for ECOG 0–1 and 2–3, respectively, HR = 0.49 (0070 < 0.001) for age≥75 years and HR = 0.59 (p = 0.007) for stage IV. Several ECOG 2–3 patients had long survival: 2-year survival was 8% for VSG patients who had ASC, compared with 0% for VSP. VeriStrat status did not predict benefit from erlotinib treatment because the HRs for erlotinib versus placebo were similar between VSG and VSP patients.ConclusionsVeriStrat was not a predictive marker for survival when considering first-line erlotinib for patients with NSCLC who had poor PS and were not recommended for platinum doublet therapies. However, VeriStrat was an independent prognostic marker of survival. It represents an objective measurement that could be considered alongside other patient factors to provide a more refined assessment of prognosis for this particular patient group. VSG patients could be selected for treatment trials because of better survival, while VSP patients can continue to be treated conservatively or offered trials of less toxic agents.Trial registration ISRCTN NumberISRCTN02370070.

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Section: Discussionsupporting

confidence: 89%

Section: Introductionmentioning

confidence: 99%

The clinical role of VeriStrat testing in patients with advanced non–small cell lung cancer considered unfit for first-line platinum-based chemotherapy

Lee

Upadhyay

Lewanski

et al. 2019

European Journal of Cancer

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“…The power of proteomics is leading to the identification of a vast number of biomarkers for numerous diseases, with a Google Scholar search of the terms “proteomics” and “biomarker” yielding 300,000 hits. Despite this number, few proteomic biomarker panels have successfully transitioned from discovery to clinical use [ 14 , 15 ], with limited examples available: OVA2 for ovarian cancer [ 16 ], VeriStrat for lung cancer [ 17 ], Vectra for rheumatoid arthritis [ 18 ].…”

Section: Discussionmentioning

confidence: 99%

The New and the Old: Platform Cross-Validation of Immunoaffinity MASS Spectrometry versus ELISA for PromarkerD, a Predictive Test for Diabetic Kidney Disease

et al. 2020

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PromarkerD is a proteomics derived test for predicting diabetic kidney disease that measures the concentrations of three plasma protein biomarkers, APOA4, CD5L and IBP3. Antibodies against these proteins were developed and applied to a multiplexed immunoaffinity capture mass spectrometry assay. In parallel, and facilitating current clinical laboratory workflows, a standard ELISA was also developed to measure each protein. The performance characteristics of the two technology platforms were compared using a cohort of 100 samples, with PromarkerD test scores demonstrating a high correlation (R = 0.97). These technologies illustrate the potential for large scale, high throughput clinical applications of proteomics now and into the future.

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“…Data from multiple studies of the VeriStrat test with patients receiving targeted therapies or chemotherapy have indicated association of the serum proteomic test classification with some tumor-related biomarkers (such as presence of sensitizing EGFR mutations), but not all of them (no association has been found with KRAS mutational status). However, even when associations have been identified, the test remained a significant predictor of outcomes in multivariate analysis and was able to stratify outcomes within tumor biomarker defined subgroups [66]. In the case of immunotherapies, the most relevant tumor/TME biomarker is PD-L1 expression.…”

Section: Independence Of Proteomic Tests From Clinical Characteristicmentioning

confidence: 99%

Mass Spectrometry-Based Multivariate Proteomic Tests for Prediction of Outcomes on Immune Checkpoint Blockade Therapy: The Modern Analytical Approach

Grigorieva

Asmellash

Net

et al. 2020

IJMS

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The remarkable success of immune checkpoint inhibitors (ICIs) has given hope of cure for some patients with advanced cancer; however, the fraction of responding patients is 15–35%, depending on tumor type, and the proportion of durable responses is even smaller. Identification of biomarkers with strong predictive potential remains a priority. Until now most of the efforts were focused on biomarkers associated with the assumed mechanism of action of ICIs, such as levels of expression of programmed death-ligand 1 (PD-L1) and mutation load in tumor tissue, as a proxy of immunogenicity; however, their performance is unsatisfactory. Several assays designed to capture the complexity of the disease by measuring the immune response in tumor microenvironment show promise but still need validation in independent studies. The circulating proteome contains an additional layer of information characterizing tumor–host interactions that can be integrated into multivariate tests using modern machine learning techniques. Here we describe several validated serum-based proteomic tests and their utility in the context of ICIs. We discuss test performances, demonstrate their independence from currently used biomarkers, and discuss various aspects of associated biological mechanisms. We propose that serum-based multivariate proteomic tests add a missing piece to the puzzle of predicting benefit from ICIs.

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Retrospective Assessment of a Serum Proteomic Test in a Phase III Study Comparing Erlotinib plus Placebo with Erlotinib plus Tivantinib (MARQUEE) in Previously Treated Patients with Advanced Non-Small Cell Lung Cancer

Cited by 11 publications

References 32 publications

The clinical role of VeriStrat testing in patients with advanced non–small cell lung cancer considered unfit for first-line platinum-based chemotherapy

The clinical role of VeriStrat testing in patients with advanced non–small cell lung cancer considered unfit for first-line platinum-based chemotherapy

The New and the Old: Platform Cross-Validation of Immunoaffinity MASS Spectrometry versus ELISA for PromarkerD, a Predictive Test for Diabetic Kidney Disease

Mass Spectrometry-Based Multivariate Proteomic Tests for Prediction of Outcomes on Immune Checkpoint Blockade Therapy: The Modern Analytical Approach

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