Comparison of clinical outcome of patients with non-small-cell lung cancer harbouring epidermal growth factor receptor exon 19 or exon 21 mutations

Won, Young‐Woong; Han, Ji‐Youn; Lee, Geon Kook; Park, Seog-Yun; Lim, Key Hwan; Yoon, Kyong–Ah; Yun, Tak; Kim, Heung Tae; Lee, Jin Soo

doi:10.1136/jclinpath-2011-200169

Cited by 65 publications

(57 citation statements)

References 34 publications

(21 reference statements)

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“…In 170 NSCLC patients with different EGFR mutations, those patients with EGFR mutations in exon 19 exhibited significantly longer progression-free survival (12.8 months) than those with mutations in exon 21 (10.6 months) (25). The finding supported the hypothesis that EGFR mutations in exon 19, especially delE746-A750, was more effective in predicting TKI sensitivity (26,27). Furthermore, delE746-A750 was identified in an ovarian cancer patient who was sensitive to the treatment of gefitinib in a Phase II study (28).…”

Section: Discussionsupporting

confidence: 78%

An epidermal growth factor receptor exon 19 mutation in a mucin-producing gastric cancer sample from a Chinese patient

Wang

et al. 2016

Jpn. J. Clin. Oncol.

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Objective: To determine whether a subgroup of gastric cancer patients might benefit from epidermal growth factor receptor-tyrosine kinase inhibitors. Methods: A total of 103 gastric cancer samples were collected for this study. High-resolution melting and deoxyribonucleic acid sequencing were used to detect epidermal growth factor receptor mutations in exons 19 and 21. Results: Polymerase chain reaction-high-resolution melting was successfully performed on all 103 samples. Aberrant melting curves were found in only one sample. Sanger sequencing revealed a 15 bp deletion (c.2235_2249del; p.Glu746_Ala750del) in epidermal growth factor receptor exon 19. The sample was from a male patient, and the pathological diagnosis was a mucin-producing gastric cancer with lymph node metastasis. To date, this is the first report on epidermal growth factor receptor exon 19 mutation in gastric cancer. Conclusions: An epidermal growth factor receptor mutation in exon 19 was identified in mucinproducing gastric cancer sample from a male patient. This mutation indicates that the small subgroup of patients with mucin-producing gastric cancer might benefit from epidermal growth factor receptor-tyrosine kinase inhibitors.

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Section: Discussionsupporting

confidence: 78%

An epidermal growth factor receptor exon 19 mutation in a mucin-producing gastric cancer sample from a Chinese patient

Wang

et al. 2016

Jpn. J. Clin. Oncol.

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“…Exon 19 deletions are associated with a better response and longer survival, both in retrospective [41,[81][82][83] and prospective series [14], but this is not found in all series [84].…”

Section: Sensitivity To First Generation Tki According To Mutation Typementioning

confidence: 92%

Management of EGFR mutated nonsmall cell lung carcinoma patients

2015

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Number 8 in the series "Challenges and controversies in thoracic oncology" Edited by J-P. Sculier, B. Besse and P. Van Schil Correspondence:Anne-Pascale Meert, Institut Jules Bordet, 1 rue Héger-Bordet, 1000 Brussels, Belgium. E-mail: ap.meert@bordet.be ABSTRACT Tyrosine kinase inhibitors (TKIs) targeting the epidermal growth factor receptor (EGFR) are common in the therapeutic armentarium of lung cancer today. Initially tested in an unselected population, they have been of limited usefulness until the identification EGFR gene mutations. Activating mutations generate conformational changes that result in a shift toward an active state of the catalytic domain and are associated with sensitivity to first generation EGFR TKI. Other mutations have been associated with resistance to these drugs, but for rare mutations there is limited data concerning their role in predicting response to EGFR TKI.To date, four molecules have been approved for the treatment of EGFR mutated lung cancer. Gefitinib and/or erlotinib are available in almost all countries. Afatinib has been approved by the US Food and Drug Administration and by the European Medicines Agency, and icotinib has been approved only in China. Other, more active, third generation agents with a higher binding affinity for the receptor, or that are directed against specific mutations, are under development. EGFR TKIs have a favourable impact on progression-free survival when given as first line treatment in mutated patients, but may also have a moderate effect as a salvage therapy and in maintenance in an unselected population.

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“…Recently, Won and colleagues summarized the differences in clinical benefits between the 2 mutation types using data from 12 studies (10) and suggested that patients with an exon 19 deletion might benefit more from gefitinib or erlotinib treatment compared with those with the L858R mutation.…”

Section: Introductionmentioning

confidence: 99%

Afatinib Prolongs Survival Compared with Gefitinib in an Epidermal Growth Factor Receptor-Driven Lung Cancer Model

Ninomiya

Takigawa

Ichihara

et al. 2013

Molecular Cancer Therapeutics

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An irreversible ErbB family blocker is expected to inhibit tumors with activating epidermal growth factor receptor (EGFR) mutations more strongly than reversible EGFR tyrosine kinase inhibitors and to overcome acquired resistance to the T790M secondary mutation. Eleven-week-old transgenic mice with Egfr exon 19 deletion mutation were treated with afatinib, gefitinib, or vehicle for 4 weeks. All mice were sacrificed at 15 weeks of age, and the number of superficial left lung tumors with a long axis exceeding 1 mm was counted. The afatinib-treated group had significantly fewer tumors than the vehicle group (P < 0.01) and tended to have fewer tumors than the gefitinib-treated group (P ¼ 0.06). Pathologically, gefitinib-treated mice had clearer, more nodular tumors than afatinib-treated mice. Immunoblotting showed that afatinib suppressed not only pEGFR but also pHER2, and induced apoptosis for longer periods than gefitinib. Subsequently, when each drug was administered 5 days per week until death, afatinib significantly enhanced mouse survival compared with gefitinib (median survival time: 456 days vs. 376.5 days; log-rank test, P < 0.01). Finally, the combination of afatinib with bevacizumab was found to be superior to either drug alone in exon 19 deletion/T790M and L858R/T790M xenograft tumors. Overall, afatinib was more potent than gefitinib in tumors harboring an exon 19 deletion mutation, and the combination of afatinib with bevacizumab efficiently suppressed tumors harboring the T790M secondary mutation. Mol Cancer Ther; 12(5); 589-97. Ó2013 AACR.

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Comparison of clinical outcome of patients with non-small-cell lung cancer harbouring epidermal growth factor receptor exon 19 or exon 21 mutations

Abstract: While no significant difference in OS was observed between EGFR exon 19 deletion and L858R mutation, EGFR exon 19 deletion was predictive of longer PFS following EGFR TKI treatment in patients with advanced NSCLC.

Cited by 65 publications

References 34 publications

An epidermal growth factor receptor exon 19 mutation in a mucin-producing gastric cancer sample from a Chinese patient

An epidermal growth factor receptor exon 19 mutation in a mucin-producing gastric cancer sample from a Chinese patient

Management of EGFR mutated nonsmall cell lung carcinoma patients

Afatinib Prolongs Survival Compared with Gefitinib in an Epidermal Growth Factor Receptor-Driven Lung Cancer Model

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