EGFR Mutations Detected in Plasma Are Associated with Patient Outcomes in Erlotinib Plus Docetaxel-Treated Non-small Cell Lung Cancer

Mack, Philip C.; Holland, William; Burich, Rebekah A.; Sangha, Randeep; Solis, Leslie; Li, Yueju; Beckett, Laurel A.; Lara, Primo N.; Davies, Angela M.; Gandara, David R.

doi:10.1097/jto.0b013e3181bbf239

Cited by 62 publications

(64 citation statements)

References 35 publications

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“…Subsequent studies have attempted to confirm these results in a larger case series (75)(76)(77)(78)(79)(80)(81)(82)(83)(84)(85)(86)(87)(88)(89). Using different methodologies, results of the majority of those studies identified identical serum/plasma, with tissue EGFR mutations being reported in >70% of patients (74)(75)(76)(77)(78)(79)(80)(81)(82)(83)(84)(85)(86)(87)(88)(89) (Table I).…”

Section: Biological Samples Suitable For Molecular Characterisationmentioning

confidence: 63%

Target therapy in NSCLC patients: Relevant clinical agents and tumour molecular characterisation

Ulivi

Zoli

Capelli

et al. 2013

Molecular and Clinical Oncology

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Abstract. In recent years, a number of new agents that target specific molecular pathways in non-small cell lung cancer (NSCLC) have been investigated. Much effort has been focused on identifying specific markers that are predictive of treatment response, given that a tailored approach would maximise the therapeutic index and cost-effectiveness. Gefitinib and erlotinib are selective epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (EGFR-TKIs) and have produced good results in selected cases in terms of objective response rate and overall survival. At present, EGFR gene mutations are considered the most important predictors of clinical response to TKI therapy and tumour characterisation for these alterations is mandatory prior to any decision making. Echinoderm microtubule-like protein 4-anaplastic lymphoma kinase (EML4-ALK) translocation is another alteration capable of predicting the efficacy of anti-ALK agents, such as crizotinib. Moreover, emerging target agents, such as MET inhibitors, are likely to increase the amount of molecular characterisation required before a decision is made on treatment. The main limiting factor for adequate characterisation of metastatic NSCLC patients is the small quantity of tumour cells available for molecular analysis. In this study, we provided an overview of the most important and clinically relevant target agents in NSCLC patients as well as the most important mechanisms of resistance. The issue of the scant amount of biological samples available for analysis as well as alternative sampling approaches such as plasma-or serum-derived DNA were also examined.

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Section: Biological Samples Suitable For Molecular Characterisationmentioning

confidence: 63%

Target therapy in NSCLC patients: Relevant clinical agents and tumour molecular characterisation

Ulivi

Zoli

Capelli

et al. 2013

Molecular and Clinical Oncology

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“…The sensitivity of direct sequencing is relatively poor and requires more mutant DNA to detect EGFR mutations in specimens (10-25% mutant DNA). The PNA-LNA PCR clamp is more sensitive and is able to detect ≥1% mutant DNA in the specimens, as is the Scorpion Amplified Refractory Mutation System (ARMS) method, which currently has kits commercially available for testing (4,10,12,14). However, direct sequencing is able to detect new mutations, while the PNA-LNA PCR clamp and the Scorpion ARMS are capable of detecting known mutations only (10,12,14).…”

Section: Discussionmentioning

confidence: 99%

“…Determination of the tumor EGFR mutation status is significant for non-squamous NSCLC, since first-line treatment with erlotinib or gefitinib is recommended for patients with EGFR-activating mutations, and cytotoxic chemotherapy is recommended for patients without an EGFR-activating mutation status or with an unknown status. The use of plasma or serum samples for EGFR mutation analysis has been actively studied recently since more than half of the patients did not have or had inadequate pathological samples for tumor EGFR mutation analysis (9,10). Several methods are used to detect EGFR mutations in lung cancer specimens (14).…”

Section: Discussionmentioning

confidence: 99%

“…Plasma-free DNA EGFR mutation analysis is a novel tool that provides an easy, convenient and safe way of testing patients, and is particularly useful for those patients who do (9)(10)(11). In the present study, we prospectively collected and examined the plasma-free DNA mutation status of our lung cancer patients with adenocarcinoma who were due to receive erlotinib treatment, to determine whether or not this method is effective in the detection of the EGFR mutation status and in the prediction of treatment response and PFS.…”

Section: Introductionmentioning

confidence: 99%

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Plasma epidermal growth factor receptor mutation analysis and possible clinical applications in pulmonary adenocarcinoma patients treated with erlotinib

et al. 2011

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Abstract. Tumor epidermal growth factor receptor (EGFR) mutation analysis is significant for making treatment decisions for metastatic pulmonary adenocarcinoma. However, less than half of patients have adequate tumor samples for mutation analysis. Patients with adenocarcinoma of the lungs who were due to receive erlotinib treatment were included in the present study. Tumor EGFR mutation status was analyzed using DNA sequencing. Plasma specimens from the patients were collected prior to erlotinib treatment. The plasma-free DNA EGFR mutation status was analyzed using the PCR clamp method. A total of 54 consecutive patients were included in the study. The plasma-free DNA EGFR mutation status of the 54 patients was analyzed. Only 30 patients had adequate tumor samples for EGFR analysis, including 15 with activating mutations (exon 19 deletions or L858R). EGFR-activating mutations were detected in the plasma-free DNA in 25 of 54 patients. The response rate was 86.7 and 33.3% in patients with and without tumor activating mutations, respectively (p=0.002). The response rate was 68 and 31% based on the patients' plasma-free DNA EGFR mutation status, respectively (p=0.013). No significant difference in progression-free survival (PFS) was observed between patients with and without EGFR-activating mutations, according to data from tumor tissue or plasma-free DNA analysis, although the median PFS time was longer for those patients with EGFR-activating mutations in plasma samples.Plasma EGFR mutation analysis is useful for adenocarcinoma patients who have no or inadequate tumor samples available for EGFR examination. Patients with plasma EGFR-activating mutations had an improved response rate and a statistically insignificant longer PFS.

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“…105 Subsequent studies have attempted to confirm these results in larger case series. [106][107][108][109][110][111][112] Indeed, using a range of different methodologies, serum/plasma EGFR mutations have been reported in over 70% of patients in which the tumor tissue showed the same mutation (Table 2).…”

Section: Biological Samples Suitable For Molecular Characterizationmentioning

confidence: 99%

Predictive molecular markers for EGFR-TKI in non-small cell lung cancer patients: new insights and critical aspects

Ulivi

Calistri

Zoli

et al. 2010

J Nucleic Acids Invest

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In recent years, a number of novel agents have been investigated that target specific molecular pathways in non-small cell lung cancer (NSCLC). A great deal of effort has been focused on identifying specific markers that predict treatment response, given that a tailored approach would maximize both the therapeutic index and the cost-effectiveness. The epidermal growth factor receptor (EGFR) pathway has emerged as a key regulator of cancer cell proliferation and invasion, and several specific EGFR inhibitors have been examined. Gefitinib and erlotinib are selective EGFR tyrosine kinase inhibitors (EGFR-TKIs), demonstrating good results in selected cases both in terms of objective response rate and of overall survival. At present, EGFR gene mutations are the best positive predictive factors for TKI therapy, and a number of other potential biomarkers are being investigated as additional positive or negative predictors of response. The correct selection of patients that could benefit from these innovative therapies, based on an accurate molecular characterization, is mandatory to provide the best clinical management. Currently, the main factor limiting the characterization of metastatic NSCLC patients is the small quantity of tumor cells available for molecular analysis. In this paper we provide an overview of the most important molecular predictive markers for EGFR-TKIs therapy in NSCLC patients, and focus attention on biological samples suitable for analysis and alternative sampling approaches such as plasma-or serum-derived DNA.

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EGFR Mutations Detected in Plasma Are Associated with Patient Outcomes in Erlotinib Plus Docetaxel-Treated Non-small Cell Lung Cancer

Cited by 62 publications

References 35 publications

Target therapy in NSCLC patients: Relevant clinical agents and tumour molecular characterisation

Target therapy in NSCLC patients: Relevant clinical agents and tumour molecular characterisation

Plasma epidermal growth factor receptor mutation analysis and possible clinical applications in pulmonary adenocarcinoma patients treated with erlotinib

Predictive molecular markers for EGFR-TKI in non-small cell lung cancer patients: new insights and critical aspects

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