EGFR expression as a predictor of survival for first-line chemotherapy plus cetuximab in patients with advanced non-small-cell lung cancer: analysis of data from the phase 3 FLEX study

Pirker, Robert; Pereira, José Rodrígues; Pawel, Joachim von; Krzakowski, Maciej; Ramlau, Rodryg; Park, Keunchil; Marinis, Filippo de; Eberhardt, Wilfried; Paz‐Ares, Luis; Störkel, Stephan; Schumacher, Karl; Heydebreck, Anja von; Çelik, I.; O’Byrne, Kenneth J.

doi:10.1016/s1470-2045(11)70318-7

Cited by 524 publications

(407 citation statements)

References 28 publications

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“…Such a trial would allow reproducible, quantitative thresholds to be set similar to those used for epidermal growth factor receptor expression in lung cancer therapy. 30 Vascular malformation, not otherwise specified b-Adrenergic receptor expression…”

Section: Discussionmentioning

confidence: 99%

β-Adrenergic receptor expression in vascular tumors

et al. 2012

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Section: Discussionmentioning

confidence: 99%

β-Adrenergic receptor expression in vascular tumors

et al. 2012

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“…Currently, scoring systems assist in determining the EGFR expression levels in tumor samples using internationally validated antibodies (12)(13)(14). The FLEX study assessed EGFR expression using an IHC scoring Reproducibility of the EGFR immunohistochemistry scores for tumor samples from patients with advanced non-small cell lung cancer system according to the intensity of cell membrane staining (scale of 0-3) (15). In a subanalysis, the EGFR expression levels determined during IHC were tested as a biomarker to evaluate the efficacy of cisplatin and vinorelbine plus cetuximab (12).…”

Section: Introductionmentioning

confidence: 99%

“…Sections (3 µm thick) were prepared and mounted onto positively-charged glass slides. Immunostaining was performed with an automated immunostainer using the EGFR pharmDx™ kit (Dako, Glostrup, Denmark), which was performed as previously described by the FLEX study (15). EGFR expression was evaluated by three senior pathologists (Department of Pathology, INCan, Mexico City, Mexico), who were blinded to the clinical outcomes.…”

Section: Introductionmentioning

confidence: 99%

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Reproducibility of the EGFR immunohistochemistry scores for tumor samples from patients with advanced non-small cell lung cancer

et al. 2016

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Abstract. Epidermal growth factor receptor (EGFR) is overexpressed in >60% of non-small cell lung cancer (NSCLC) cases. In combination with radiotherapy or chemotherapy, first-line treatments with antibodies against EGFR, including cetuximab and necitumumab, have demonstrated benefits by increasing overall survival (OS), particularly in patients who overexpress EGFR. The present study evaluated the interobserver agreement among three senior pathologists, who were blinded to the clinical outcomes and assessed tumor samples from 85 patients with NSCLC using the H-score method. EGFR immunohistochemistry was performed using a qualitative immunohistochemical kit. The reported (mean ± standard deviation) H-scores from each pathologist were 111±102, 127±103 and 128.53±104.03. The patients with average H-scores ≥1, ≥100, ≥200 and between 250-300 were 85.9, 54.1, 28.2 and 12.9, respectively. Patients who had an average H-score >100 had a shorter OS time compared with those with lower scores. Furthermore, patients with EGFR mutations who were treated with EGFR-tyrosine kinase inhibitors (TKIs) and had an average H-score >100 had a longer OS time compared with those with an average H-score <100. The interobserver concordance for the total H-scores were 0.982, 0.980 and 0.988, and for a positive H-score ≥200, the interobserver concordance was 0.773, 0.710 and 0.675, respectively. The determination of EGFR expression by the H-score method is highly reproducible among pathologists and is a prognostic factor associated with a poor OS in all patients. Additionally, the results of the present study suggest that patients with EGFR mutations that are treated with EGFR-TKIs and present with a high H-score have a longer OS time.

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“…5 Large randomized clinical trials demonstrated a benefit from the introduction of the antiangiogenic drug bevacizumab in combination therapy, 6 as well as cetuximab in patients with epidermal growth factor receptoreexpressing tumors. 7,8 Furthermore, small-molecule inhibitors, such as gefitinib 9 or crizotinib, 10 are options for NSCLC patients with epidermal growth factor receptor mutations or echinoderm microtubule-associated protein-like 4eanaplastic lymphoma kinase translocations, respectively. However, despite improvements in therapeutic approaches, the survival expectation for patients with advanced NSCLC remains only 16 to 24 months.…”

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confidence: 99%

Interleukin-11 Receptor Is a Candidate Target for Ligand-Directed Therapy in Lung Cancer

Cardó-Vila

Marchiò

Sato

et al. 2016

The American Journal of Pathology

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We previously isolated an IL-11emimic motif (CGRRAGGSC) that binds to IL-11 receptor (IL-11R) in vitro and accumulates in IL-11Reexpressing tumors in vivo. This synthetic peptide ligand was used as a tumortargeting moiety in the rational design of BMTP-11, which is a drug candidate in clinical trials. Here, we investigated the specificity and accessibility of IL-11R as a target and the efficacy of BMTP-11 as a ligandtargeted drug in lung cancer. We observed high IL-11R expression levels in a large cohort of patients (n Z 368). In matching surgical specimens (i.e., paired tumors and nonmalignant tissues), the cytoplasmic levels of IL-11R in tumor areas were significantly higher than in nonmalignant tissues (n Z 36; P Z 0.003). Notably, marked overexpression of IL-11R was observed in both tumor epithelial and vascular endothelial cell membranes (n Z 301; P < 0.0001). BMTP-11 induced in vitro cell death in a representative panel of human lung cancer cell lines. BMTP-11 treatment attenuated the growth of subcutaneous xenografts and reduced the number of pulmonary tumors after tail vein injection of human lung cancer cells in mice. Our findings validate BMTP-11 as a pharmacologic candidate drug in preclinical models of lung cancer and patient-derived tumors. Moreover, the high expression level in patients with non-small cell lung cancer is a promising feature for potential translational applications. (Am J Pathol 2016, 186: 2162e2170; http://dx

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EGFR expression as a predictor of survival for first-line chemotherapy plus cetuximab in patients with advanced non-small-cell lung cancer: analysis of data from the phase 3 FLEX study

Cited by 524 publications

References 28 publications

β-Adrenergic receptor expression in vascular tumors

β-Adrenergic receptor expression in vascular tumors

Reproducibility of the EGFR immunohistochemistry scores for tumor samples from patients with advanced non-small cell lung cancer

Interleukin-11 Receptor Is a Candidate Target for Ligand-Directed Therapy in Lung Cancer

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