Journal ArticleDOI
Predictive and Prognostic Impact of Epidermal Growth Factor Receptor Mutation in Non–Small-Cell Lung Cancer Patients Treated With Gefitinib
Sae-Won Han,Tae-You Kim,Pil Gyu Hwang,Soohyun Jeong,Jeongmi Kim,In Sil Choi,Do Youn Oh,Jee Hyun Kim,Dong Wan Kim,Doo Hyun Chung,Seock-Ah Im,Young Tae Kim,Jong-Seok Lee,Dae Seog Heo,Yung-Jue Bang,Noe Kyeong Kim +15 more
TLDR
P-Akt overexpression was associated with prolonged TTP in patients with EGFR mutation, which further support the importance of EGFR mutations with regard to gefitinib sensitivity.Abstract:
Purpose This study was undertaken to investigate the effects of epidermal growth factor receptor (EGFR) mutation and its downstream signaling on response and survival in non–small-cell lung cancer (NSCLC) patients treated with gefitinib. Patients and Methods For 90 consecutive NSCLC patients who had received gefitinib, EGFR mutation was analyzed by DNA sequencing of exons 18, 19, 21, and 23 in the EGFR tyrosine kinase domain. Expressions of phosphorylated (p) -Akt and p-Erk were determined via immunohistochemistry. Response rate, time to progression (TTP), and overall survival were compared between each group according to EGFR mutation, as well as p-Akt and p-Erk expression. Results Seventeen patients (18.9%; 95% CI, 10.8 to 27.0) harbored EGFR mutations. These mutations include deletions in exon 19 in seven patients, L858R in six patients, G719A in three patients, and a novel A859T in one patient. Response rate in patients with EGFR mutation was 64.7% (11 of 17 patients; 95% CI, 42.0 to 87.4), in contras...read more
Citations
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Journal ArticleDOI
Gefitinib or Carboplatin–Paclitaxel in Pulmonary Adenocarcinoma
Tony Mok,Yi-Long Wu,Sumitra Thongprasert,Chih-Hsin Yang,Da Tong Chu,Nagahiro Saijo,Patrapim Sunpaweravong,Baohui Han,Benjamin Margono,Benjamin Margono,Yukito Ichinose,Yutaka Nishiwaki,Yuichiro Ohe,Jin Ji Yang,Busyamas Chewaskulyong,Haiyi Jiang,Emma Duffield,Claire Watkins,Alison Armour,Masahiro Fukuoka +19 more
TL;DR: Gefit inib is superior to carboplatin-paclitaxel as an initial treatment for pulmonary adenocarcinoma among nonsmokers or former light smokers in East Asia and the presence in the tumor of a mutation of the EGFR gene is a strong predictor of a better outcome with gefitinib.
Journal ArticleDOI
Erlotinib in previously treated non-small-cell lung cancer.
Frances A. Shepherd,José Rodrigues Pereira,Tudor Ciuleanu,Eng Huat Tan,Vera Hirsh,Sumitra Thongprasert,Daniel Campos,Savitree Maoleekoonpiroj,Michael Smylie,Renato G. Martins,Maximiliano Van Kooten,Mircea Dediu,B. Findlay,Dongsheng Tu,Dianne Johnston,Andrea Bezjak,Gary M. Clark,Pedro Santabárbara,Lesley Seymour +18 more
TL;DR: Elotinib can prolong survival in patients with non-small-cell lung cancer after first-line or second-line chemotherapy, and five percent of patients discontinued erlot inib because of toxic effects.
Journal ArticleDOI
Epidermal growth factor receptor mutations in lung cancer
TL;DR: 'oncogenic shock' is described as a mechanistic explanation for the apoptosis that follows the acute treatment of susceptible cells with kinase inhibitors, essential to the successful use of targeted therapies in common epithelial cancers.
Journal ArticleDOI
Screening for Epidermal Growth Factor Receptor Mutations in Lung Cancer
Rafael Rosell,Teresa Moran,Cristina Queralt,Rut Porta,Felipe Cardenal,Carlos Camps,Margarita Majem,Guillermo Lopez-Vivanco,Dolores Isla,Mariano Provencio,A. Insa,Bartomeu Massuti,José Luis González-Larriba,Luis Paz-Ares,Isabel Bover,Rosario García-Campelo,Miguel Angel Moreno,Silvia Catot,Christian Rolfo,Noemi Reguart,Ramon Palmero,Jose Miguel Sanchez,Roman Bastus,Clara Mayo,Jordi Bertran-Alamillo,Miguel Angel Molina,Jose Javier Sanchez,Miquel Taron +27 more
TL;DR: Large-scale screening of patients with lung cancer for EGFR mutations is feasible and can have a role in decisions about treatment, and the association between the mutations and the outcome of erlotinib treatment is analyzed.
Journal ArticleDOI
Erlotinib in lung cancer - molecular and clinical predictors of outcome.
Ming-Sound Tsao,Akira Sakurada,Jean-Claude Cutz,Jean-Claude Cutz,Chang-Qi Zhu,Chang-Qi Zhu,Suzanne Kamel-Reid,Suzanne Kamel-Reid,Jeremy A. Squire,Jeremy A. Squire,Ian A. J. Lorimer,Tong Zhang,Tong Zhang,Ni Liu,Ni Liu,Manijeh Daneshmand,Paula Marrano,Paula Marrano,Gilda da Cunha Santos,Gilda da Cunha Santos,Alain E. Lagarde,Frank C. Richardson,Lesley Seymour,Marlo Whitehead,Keyue Ding,Joseph L. Pater,Frances A. Shepherd,Frances A. Shepherd +27 more
TL;DR: Among patients with non-small-cell lung cancer who receive erlotinib, the presence of an EGFR mutation may increase responsiveness to the agent, but it is not indicative of a survival benefit.
References
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Journal ArticleDOI
Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small-cell lung cancer to gefitinib
Thomas J. Lynch,Daphne W. Bell,Raffaella Sordella,Sarada Gurubhagavatula,Ross A. Okimoto,Brian W. Brannigan,Patricia L. Harris,Sara M. Haserlat,Jeffrey G. Supko,Frank G. Haluska,David N. Louis,David C. Christiani,Jeff Settleman,Daniel A. Haber +13 more
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Journal ArticleDOI
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Journal ArticleDOI
EGF receptor gene mutations are common in lung cancers from “never smokers” and are associated with sensitivity of tumors to gefitinib and erlotinib
William Pao,Vincent A. Miller,Maureen F. Zakowski,Jennifer Doherty,Katerina Politi,Inderpal S. Sarkaria,Bhuvanesh Singh,Robert T. Heelan,Valerie W. Rusch,Lucinda Fulton,Elaine R. Mardis,Doris M. Kupfer,Richard K. Wilson,Mark G. Kris,Harold E. Varmus +14 more
TL;DR: Data show that adenocarcinomas from never smokers comprise a distinct subset of lung cancers, frequently containing mutations within the TK domain of EGFR that are associated with gefitinib and erlotinib sensitivity.
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