EGFR Molecular Profiling in Advanced NSCLC: A Prospective Phase II Study in Molecularly/Clinically Selected Patients Pretreated with Chemotherapy

Milella, Michèle; Nuzzo, Carmen; Bria, Emilio; Sperduti, Isabella; Visca, P.; Buttitta, Fiamma; Antoniani, Barbara; Merola, Roberta; Cuppone, Federica; D'Alicandro, Valerio; Ceribelli, Anna; Rinaldi, Massimo; Cianciulli, Anna Maria; Felicioni, Lara; Malatesta, Sara; Marchetti, Antonio; Mottolese, Marcella; Cognetti, Francesco

doi:10.1097/jto.0b013e31824a8bde

Cited by 26 publications

(33 citation statements)

References 46 publications

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“…1). Finally, 12 prospective intervention trials (Brugger et al 2011;Cappuzzo et al 2007;Douillard et al 2010;Giaccone et al 2006;Hirsch et al 2006Hirsch et al , 2011Karampeazis et al 2013;Milella et al 2012;Miller et al 2008;Ramalingam et al 2011;Schneider et al 2008;Zhu et al 2008) were included in the meta-analysis of the unselected advanced NSCLC with a total of 1,859 patients (ranging from 29 to 493 patients per study) who were available for KRAS gene status evaluation, and of whom 342 had KRAS mutations (18.4 %). Baseline characteristics of these eligible trials were summarized in Table 1.…”

Section: Study Characteristicsmentioning

confidence: 99%

Should KRAS mutation still be used as a routine predictor of response to EGFR-TKIs in advanced non-small-cell lung cancer? A revaluation based on meta-analysis

Ying

Zhu

Chen

et al. 2015

J Cancer Res Clin Oncol

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Section: Study Characteristicsmentioning

confidence: 99%

Should KRAS mutation still be used as a routine predictor of response to EGFR-TKIs in advanced non-small-cell lung cancer? A revaluation based on meta-analysis

Ying

Zhu

Chen

et al. 2015

J Cancer Res Clin Oncol

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“…The use of molecular selection markers, other than epidermal growth factor receptor (EGFR) mutation testing for EGFR-tyrosine kinase inhibitor (TKI) treatment assignment, remains speculative at present, particularly for patients who have already undergone first-line chemotherapy for advanced stages of the disease (2). However, clinical experience, clinical and metrological data and findings at the molecular biology level all indicate that the occurrence of resistance is a constraint on the further use of TKIs and represents a bottleneck (3).…”

Section: Introductionmentioning

confidence: 99%

Paris saponin I induces apoptosis via increasing the Bax/Bcl-2 ratio and caspase-3 expression in gefitinib-resistant non-small cell lung cancer in vitro and in vivo

Jiang

Zhao

et al. 2014

Molecular Medicine Reports

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Abstract. Polyphyllins, a major component of Rhizoma paridis, have been extensively used in non-small cell lung cancer (NSCLC). The aim of the present study was to evaluate the effects of Paris saponin I (PSI) on a panel of gefitinib-resistant NSCLC cell lines and its inhibition of tumor growth in a nude mouse model. The MTT assay was used to assess growth inhibition. The cell cycle was analyzed using flow cytometry and apoptosis was assessed using Annexin V/propidium iodide staining. The morphology of the apoptotic cells was determined by transmission electron microscopy. The protein expression levels of B-cell lymphoma 2 (Bcl-2), Bcl-2-associated X protein (Bax) and caspase-3 were detected using western blot analysis. In addition, the glucose metabolism in tumor-bearing mice was evaluated using 18 F-fludeoxyglucose (FDG) micro-positron emission tomography imaging. The PSI-induced growth inhibition rate was observed to significantly increase in a time-and dose-dependent manner. Furthermore, PSI induced significant G2/M-phase arrest and apoptosis. The expression levels of Bcl-2 decreased, while those of Bax and caspase-3 increased following PSI treatment.18 F-FDG-uptake in the PSI treatment groups was significantly decreased compared with that in the control group in vivo. In conclusion, PSI is a potent antitumor agent that acts by inhibiting the proliferation of gefitinib-resistant cells, and has potential as a candidate for a natural drug for gefitinib-resistant therapy. PSI-induced apoptosis, which occurred via multiple pathways, including G2/M-phase arrest and upregulation of the Bax/Bcl-2 ratio and caspase-3 expression, ultimately led to cell death and tumor inhibition.

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“…In addition, progression-free survival (PFS) and overall survival (OS) were significantly better for EGFR-TKI-treated patients with EGFR mutations than those with EGFR wildtype. Moreover, EGFR-mutated patients treated in the maintenance setting had a large benefit in term of PFS (3,4). The clinical relevance of EGFR mutational status has been deeply discussed in recent years and testing for these mutations has rapidly become a standard practice.…”

Section: Introductionmentioning

confidence: 99%

Effective Assessment of egfr Mutation Status in Bronchoalveolar Lavage and Pleural Fluids by Next-Generation Sequencing

Buttitta

Felicioni

Grammastro

et al. 2013

Clinical Cancer Research

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110

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Purpose: The therapeutic choice for patients with lung adenocarcinoma depends on the presence of EGF receptor (EGFR) mutations. In many cases, only cytologic samples are available for molecular diagnosis. Bronchoalveolar lavage (BAL) and pleural fluid, which represent a considerable proportion of cytologic specimens, cannot always be used for molecular testing because of low rate of tumor cells.Experimental Design: We tested the feasibility of EGFR mutation analysis on BAL and pleural fluid samples by next-generation sequencing (NGS), an innovative and extremely sensitive platform. The study was devised to extend the EGFR test to those patients who could not get it due to the paucity of biologic material. A series of 830 lung cytology specimens was used to select 48 samples (BAL and pleural fluid) from patients with EGFR mutations in resected tumors. These samples included 36 cases with 0.3% to 9% of neoplastic cells (series A) and 12 cases without evidence of tumor (series B). All samples were analyzed by Sanger sequencing and NGS on 454 Roche platform. A mean of 21,130 AE 2,370 sequences per sample were obtained by NGS.Results: In series A, EGFR mutations were detected in 16% of cases by Sanger sequencing and in 81% of cases by NGS. Seventy-seven percent of cases found to be negative by Sanger sequencing showed mutations by NGS. In series B, all samples were negative for EGFR mutation by Sanger sequencing whereas 42% of them were positive by NGS.Conclusions: The very sensitive EGFR-NGS assay may open up to the possibility of specific treatments for patients otherwise doomed to re-biopsies or nontargeted therapies.

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EGFR Molecular Profiling in Advanced NSCLC: A Prospective Phase II Study in Molecularly/Clinically Selected Patients Pretreated with Chemotherapy

Abstract: Selection of patients based on either EGFR mutation or clinical characteristics seems an effective approach to optimize EGFR-TKI treatment in chemotherapy-pretreated non-small-cell lung cancer patients.

Cited by 26 publications

References 46 publications

Should KRAS mutation still be used as a routine predictor of response to EGFR-TKIs in advanced non-small-cell lung cancer? A revaluation based on meta-analysis

Should KRAS mutation still be used as a routine predictor of response to EGFR-TKIs in advanced non-small-cell lung cancer? A revaluation based on meta-analysis

Paris saponin I induces apoptosis via increasing the Bax/Bcl-2 ratio and caspase-3 expression in gefitinib-resistant non-small cell lung cancer in vitro and in vivo

Effective Assessment of egfr Mutation Status in Bronchoalveolar Lavage and Pleural Fluids by Next-Generation Sequencing

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