Clinical Impact of two Different Diagnostic Strategies in the First- and Second-Line Treatment of Locally Advanced or Metastatic EGFR-Mutated Non-Small Cell Lung Cancer

BACKGROUND: A histopathological and mutational diagnosis has become a priority in the correct choice of the most appropriate cancer therapy for NSCLC. In the absence of a molecular analysis, the therapeutic choice will be directed towards platinum-based chemotherapy, thus preventing, in the presence of a specific mutation, the benefits deriving from the administration of a target therapies (TT).AIM: the present analysis was carried out with the aim of estimating the clinical impact, expressed in terms of progression free survival (PFS), associated with the use of the combined strategy (tissue biopsy and liquid biopsy) or the tissue strategy in the EGFR+ mNSCLC population.METHODS: A pre-existing cost-consequence model was adapted to estimate the annual number of mNSCLC patients with or without the EGFR mutation in order to decide the oncological treatment to be administered in first (1L) or second line (2L). In 1L, against the presence of the EGFR mutation, the administration of a Tyrosine Kinase Inhibitor (TKI), such as osimertinib, gefitinib, erlotinib or afatinib, was considered; in the absence of the EGFR mutation, the administration ofstandard platinum-based chemotherapy was instead considered. With reference to 2L, in the presence of the EGFR T790M mutation, only osimertinib was considered. In the absence of the EGFR T790M mutation, the administration of the standard platinum-based chemotherapy was also considered. The PFS data associated with each of the drugs considered were extrapolated from the respective clinical studies. Key variables were tested in the sensitivity analysis.RESULTS: The adoption of the combined strategy (tissue biopsy and liquid biopsy), by virtue of a greater number of patients treated with TKIs, would make it possible to increase the average PFS in the range of 1.1-3,7 months in the 1L and by 1.4 months in the 2L.CONCLUSION: These results show how the adoption of a correct diagnostic strategy is critical in order to optimize the choice of the therapeutic path in the 1L and 2L of mNSCLC. The addition of the liquid biopsy to the classic diagnostic path (tissue biopsy) would in fact allow to obtain an increase in therapeutic efficacy (average PFS).

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Cost-Consequence Analysis of Three Different Diagnostic Strategies in the First- and Second-Line Treatment of Locally Advanced or Metastatic Non-Small-Cell Lung Cancer

Farmeconomia Health economics and therapeutic pathways ◽

10.7175/fe.v19i1.1354 ◽

2018 ◽

Vol 19 (1) ◽

Cited By ~ 2

Author(s):

Giovanni Gancitano ◽

Roberto Ravasio ◽

Matteo Dionisi ◽

Diego Cortinovis

Keyword(s):

Liquid Biopsy ◽

Locally Advanced ◽

Cost Effective ◽

Line Treatment ◽

Second Line ◽

Diagnostic Strategies ◽

Tissue Biopsy ◽

Cost Consequence ◽

Potential Strategy ◽

Combined Strategy

BACKGROUND: Unlike the tissue one, liquid biopsy is a less invasive diagnostic method for the assessment of possible mutations of the tumor, based on the analysis of circulating free DNA (cfDNA) present in the plasma component of the blood. Because blood samples are easily obtainable, plasma biopsy is a non-invasive method, supplementing the more traditional biopsy techniques.AIM: A cost-consequence analysis was conducted to compare the adoption of three different diagnostic strategies in the first- and second-line treatment of locally advanced or metastatic NSCLC: i) tissue strategy (only tissue biopsy for first and second line), ii) combined strategy (first line: tissue biopsy. If unknown, liquid biopsy; second line: liquid biopsy. If negative, tissue biopsy) and iii) potential strategy (first line: tissue biopsy. If unknown or tissue ineligible, liquid biopsy; secondline: liquid biopsy. If negative, tissue biopsy).METHODS: A decision-analytic model was developed considering the Italian NHS’s perspective. We only evaluated direct medical costs (tissue biopsy, management of complications associated with tissue and liquid biopsies) borne by the NHS. The CCA was conducted over a time horizon of 1 year, assuming that for each patient with mNSCLC the diagnosticpathway (first- and second-line treatment) ended within such period. Key variables were tested in the sensitivity analysis.RESULTS: Considering both the first and the second line of treatment, the potential strategy constitutes the cost-effective alternative, characterized by an average cost per correctly identified case (€ 685) lower than that estimated for the combined strategy (€ 732) or for the tissue strategy (€ 1,004). The potential strategy remains cost-effective, also considering the results referred to the first- or second-line treatment only.CONCLUSION: The choice of a correct diagnostic strategy is crucial in order to optimize cancer therapies in the first- and second-line treatment of locally advanced or metastasized NSCLC. The addition to the diagnostic pathway of the liquid biopsy would correctly identify a greater number of cases, supporting the prescription of the best oncological therapy.

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Liquid-Biopsy-Based Identification of EGFR T790M Mutation-Mediated Resistance to Afatinib Treatment in Patients with Advanced EGFR Mutation-Positive NSCLC, and Subsequent Response to Osimertinib

Targeted Oncology ◽

10.1007/s11523-018-0612-z ◽

2018 ◽

Vol 14 (1) ◽

pp. 75-83 ◽

Cited By ~ 33

Author(s):

Maximilian J. Hochmair ◽

Anna Buder ◽

Sophia Schwab ◽

Otto C. Burghuber ◽

Helmut Prosch ◽

...

Keyword(s):

Liquid Biopsy ◽

Egfr Mutation ◽

T790m Mutation ◽

Subsequent Response ◽

Egfr T790m

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P2.03-016 Clinical Utility of Liquid Biopsy for Detecting EGFR T790M Mutation Is Very Limited

Journal of Thoracic Oncology ◽

10.1016/j.jtho.2017.09.1267 ◽

2017 ◽

Vol 12 (11) ◽

pp. S2133

Author(s):

T. Sakamoto ◽

K. Yamane ◽

N. Tanaka ◽

M. Yanai ◽

H. Izumi ◽

...

Keyword(s):

Liquid Biopsy ◽

Clinical Utility ◽

T790m Mutation ◽

Egfr T790m

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Making the case for EGFR TKI sequencing in EGFR mutation-positive NSCLC: a GioTag study US patient analysis

Future Oncology ◽

10.2217/fon-2020-0188 ◽

2020 ◽

Author(s):

Bruce Feinberg ◽

Balazs Halmos ◽

Rasim Gucalp ◽

Wenbo Tang ◽

Barbara Moehring ◽

...

Keyword(s):

Egfr Mutation ◽

De Novo ◽

Growth Factor Receptor ◽

T790m Mutation ◽

Clinical Trial Registration ◽

Evidence Based Treatment ◽

Time To Treatment Failure ◽

Epidermal Growth ◽

Egfr Tki ◽

Egfr T790m

Aim: To assess time-to-treatment failure (TTF) in US patients with epidermal growth factor receptor ( EGFR) mutation-positive non-small-cell lung cancer (NSCLC) who received sequential afatinib–osimertinib treatment in the global, observational GioTag study. Patients & methods: Patients had EGFR T790M mutation-positive disease after first-line afatinib and subsequently received osimertinib. The primary outcome was TTF. Results: In 129 patients at US centers, median TTF was 28.4 months (90% CI: 27.0–34.1). Median overall survival was 47.6 months (90% CI: 35.5–51.5). Conclusion: Sequential afatinib–osimertinib in this US-treated population was associated with long median TTF and represents an effective, evidence-based treatment option for US patients with EGFR mutation-positive NSCLC not presenting with active brain metastases or de novo T790M. Clinical Trial Registration: NCT03370770 (ClinicalTrials.gov)

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Liquid biopsy for detection of EGFR T790M mutation in nonsmall cell lung cancer

Journal of the Chinese Medical Association ◽

10.1097/jcma.0000000000000100 ◽

2019 ◽

Vol 82 (6) ◽

pp. 473-476 ◽

Cited By ~ 1

Author(s):

Hsiang-Ling Ho ◽

Chao-Cheng Huang ◽

Wen-Hui Ku ◽

Chung-Liang Ho ◽

Chia-Hung Lin ◽

...

Keyword(s):

Lung Cancer ◽

Cell Lung Cancer ◽

Liquid Biopsy ◽

Nonsmall Cell Lung Cancer ◽

T790m Mutation ◽

Egfr T790m

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Erlotinib: How to increase the duration of effective use of tyrosine kinase inhibitors in non-small cell lung cancer with EGFR mutation

Medical Council ◽

10.21518/2079-701x-2021-9-42-47 ◽

2021 ◽

pp. 42-47

Author(s):

E. I. Borisova ◽

S. L. Gutorov

Keyword(s):

Tyrosine Kinase ◽

First Generation ◽

Kinase Inhibitors ◽

Egfr Mutation ◽

Kinase Inhibitor ◽

Small Cell ◽

Second Line ◽

Small Cell Lung ◽

First Line ◽

T790m Mutation

Tyrosine kinase inhibitors of the first, second and third generations are the main treatment method for non-small cell lung cancer with EGFR mutation. About 60% of patients progressing on a first-generation or second-generation tyrosine kinase inhibitor acquire T790M mutation. An alternative is first-line osimertinib, but second-line treatment options are limited, and therefore it is important to find a strategy that allows to extend the effective treatment of TKI. One of the rational approaches is the use of a combination of a first-generation tyrosine kinase inhibitor with anti-VEGF agents. The available information sources show an increase in the effectiveness of the combined use of erlotinib and antiangiogenic drugs-bevacizumab and ramucirumab. The combination of erlotinib and bevacizumab in several studies of the second — third phase, led to a statistically significant increase in progression-free survival, but did not show a significant increase in overall survival. In the Phase 3 RELAY study, the combination of erlotinib and ramucirumab showed comparable efficacy with the third-generation TKI — osimertinib in the first line, however, overall survival results are not yet available. At the same time, there are more opportunities to choose the secondline mode, taking into account the known frequency of detection of the T790M mutation. The optimal treatment sequence is discussed, with the option of prescribing a combination of erlotinib with bevacizumab or ramucirumab in the first line and osimertinib in the second in the presence of the T790M mutation. In such patients, osimertinib may be prescribed in the second line.

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The Diagnostic Accuracy of Liquid Biopsy in EGFR-Mutated NSCLC: A Systematic Review and Meta-Analysis of 40 Studies

SLAS TECHNOLOGY Translating Life Sciences Innovation ◽

10.1177/2472630320939565 ◽

2020 ◽

pp. 247263032093956

Author(s):

Naiqun Wang ◽

Xiaolian Zhang ◽

Feilong Wang ◽

Min Zhang ◽

Bo Sun ◽

...

Keyword(s):

Sensitivity And Specificity ◽

Liquid Biopsy ◽

Egfr Mutation ◽

Egfr Mutations ◽

Cochrane Library ◽

Asian Studies ◽

Tissue Biopsy ◽

Meta Regression ◽

Blood Biopsy ◽

Nsclc Patients

Epidermal growth factor receptor (EGFR) mutations are the most common carcinogenic driver mutations in non-small-cell lung cancer (NSCLC) patients, while invasive tissue biopsy has certain inherent defects. PubMed, Ovid Medline, Embase, and the Cochrane Library were systematically searched on January 4, 2020, using the keywords “liquid biopsy,” “EGFR,” and “NSCLC.” The pooled sensitivity and specificity of EGFR mutations in paired tissue and blood were calculated. The accuracy was assessed by receiver operating characteristic curve. The meta-regression of the subgroup was performed to analyze the heterogeneity. Hazard ratio (HR) and 95% confidence interval (CI) were combined for evaluating the impact of EGFR mutation in tissue and liquid blood biopsy. A total of 40 studies with 5,995 patients were involved in the study. The pooled sensitivity was 68% (95% CI = 60–75%), and the specificity was 98% (95% CI = 95–99%). The diagnostic odds ratio was 88 (95% CI = 40–195), and the area under the curve was 0.91 (95% CI = 0.88–0.93). In the meta-regression, the sensitivity and specificity remain lower in the Asian studies than non-Asian studies (sensitivity: 66% vs. 73%, P = 0.04; specificity: 96% vs. 97%, P = 0.03, respectively). The EGFR mutation was associated with a better progression-free survival than wild type in both tissue (HR = 0.54, 95% CI = 0.34–0.85, P = 0.007) and blood (HR = 0.81, 95% CI = 0.71–0.92, P = 0.001) detection. Peripheral blood liquid biopsy had a better specificity for detecting EGFR mutation in NSCLC patients, while tissue biopsy still needs to be undertaken for negative blood biopsy patients due to its lower sensitivity.

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EGFR status evaluation by liquid biopsy during first-line therapy in patients with advanced NSCLC.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.15_suppl.e20524 ◽

2017 ◽

Vol 35 (15_suppl) ◽

pp. e20524-e20524

Author(s):

Francesca Zanelli ◽

Maria Pagano ◽

Candida Bonelli ◽

Bruno Casali ◽

Alberto Cavazza ◽

...

Keyword(s):

Disease Progression ◽

Liquid Biopsy ◽

Egfr Mutation ◽

Advanced Nsclc ◽

First Line ◽

Liquid Biopsies ◽

T790m Mutation ◽

First Line Therapy ◽

Line Therapy ◽

Nsclc Patients

e20524 Background: over the past decade, personalized management based on the molecular features of tumours in patients with advanced non small-cell lung cancer (NSCLC) has entered routine clinical practice. The poor performance of many advanced NSCLC patients may limit invasive biopsies. The liquid biopsy is a diagnostic procedure performed on cancer-derived material obtained in blood samples. In this abstract, we will describe our experience with liquid biopsies. Methods: In the Reggio Emilia Clinical Cancer Centrefrom March 2016 to December 2016, 42 patients with advanced NSCLC were analyzed that had had or had already started first line therapy. The liquid biopsy was repeated at each imaging response evaluation by thoracic-abdominal compound tomography (CT) scan performed every 3 months. In the liquid biopsy, the mutational status of EGFR was analyzed with real time PCR (KIT cobas EGFR mutation test v2 CE-IVD Roche); in tissue, it was evaluated by pyrosequencing. Results: 21/42 liquid biopsies were EGFR-mutated (12/21 eson 19 and 9/21 eson 21). In 3/21 (14.3%) cases, the tissue biopsies showed wild type (WT) EGFR. 6 liquid biopsies were also performed at time 0 (diagnosis). All liquid biopsies of EGFR WT remained WT during treatment and imaging evaluation. The median number of liquid biopsy tests for patients was 2 (range 1-3). In 4/21 cases, T790M was performed: 3 cases in both liquid biopsies and tissue, and 1 case in tissue but not in liquid biopsy. TKi therapy was ineffective in this patient with T790M mutation detected in tissue, but not in liquid biopsy. In all patients, the disappearance of the T790M mutation during TKi therapy was related to disease progression. In 11 cases, modification of EGFR mutation status during treatment anticipated CT scan evidence of disease progression (median = three months). Conclusions: the liquid biopsy is an excellent resource. In our experience the liquid biopsy is the sensitive method of choice during treatment of advanced NSCLC patients. EGFR modification status during TKi therapy showed advanced disease progression.

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