Brain metastases from lung cancer responding to erlotinib: the importance of EGFR mutation
R. Porta,J.M. Sánchez-Torres,Luis Paz-Ares,Bartomeu Massuti,Noemi Reguart,Clara Mayo,Pilar Lianes,Cristina Queralt,V. Guillem,Pablo Herrera Salinas,Silvia Catot,Dolores Isla,A. Pradas,Alfonso Gurpide,J. de Castro,E Polo,Teresa Puig,Miquel Taron,Ramon Colomer,Rafael Rosell +19 more
TLDR
Erlotinib is active in brain metastases from NSCLC; this clinical benefit is related to the presence of activating mutations in exons 19 or 21 of the EGFR gene.Abstract:
Median survival of patients with brain metastases from nonsmall cell lung cancer (NSCLC) is poor and more effective treatments are urgently needed. We have evaluated the efficacy of erlotinib in this setting and its association with activating mutations in the epidermal growth factor receptor (EGFR) gene. We retrospectively identified patients with NSCLC and brain metastases treated with erlotinib. EGFR mutations in exons 19 and 21 were analysed by direct sequencing. Efficacy and tolerability were compared according to EGFR mutational status. 69 NSCLC patients with brain metastases were identified, 17 of whom harboured EGFR mutations. Objective response rate in patients with EGFR mutations was 82.4%; no responses were observed in unselected patients (p<0.001). Median (95% CI) time to progression within the brain for patients harbouring EGFR mutations was 11.7 (7.9-15.5) months, compared to 5.8 (5.2-6.4) months for control patients whose EGFR mutational status had not been assessed (p<0.05). Overall survival was 12.9 (6.2-19.7) months and 3.1 (2.5-3.9) months (p<0.001), respectively. The toxicity of erlotinib was as expected and no differences between cohorts were observed. Erlotinib is active in brain metastases from NSCLC; this clinical benefit is related to the presence of activating mutations in exons 19 or 21 of the EGFR gene.read more
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AZD9291, an irreversible EGFR TKI, overcomes T790M-mediated resistance to EGFR inhibitors in lung cancer
Darren Cross,Susan Ashton,Serban Ghiorghiu,Cath Eberlein,Caroline A. Nebhan,Paula J. Spitzler,Jonathon P. Orme,M. Raymond V. Finlay,Richard A. Ward,Martine J. Mellor,Gareth D Hughes,Amar Rahi,Vivien Jacobs,Monica Red Brewer,Eiki Ichihara,Jing Sun,Hailing Jin,Peter Ballard,Katherine Al-Kadhimi,Rachel Rowlinson,Teresa Klinowska,Graham Richmond,Mireille Cantarini,Dong Wan Kim,Malcolm R Ranson,William Pao +25 more
TL;DR: A novel structurally distinct third-generation EGFR TKI that irreversibly and selectively targets both sensitizing and resistant T790M(+) mutant EGFR while harboring less activity toward wild-type EGFR is reported.
Journal ArticleDOI
Molecular Testing Guideline for Selection of Lung Cancer Patients for EGFR and ALK Tyrosine Kinase Inhibitors: Guideline from the College of American Pathologists, International Association for the Study of Lung Cancer, and Association for Molecular Pathology
Neal I. Lindeman,Philip T. Cagle,Mary Beth Beasley,Dhananjay Chitale,Sanja Dacic,Giuseppe Giaccone,Robert Brian Jenkins,David J. Kwiatkowski,Juan Sebastian Saldivar,Jeremy A. Squire,Erik Thunnissen,Marc Ladanyi +11 more
TL;DR: 37 guideline items address 14 subjects, including 15 recommendations (evidence grade A/B), to use testing for EGFR mutations and ALK fusions to guide patient selection for therapy with an epidermal growth factor receptor (EGFR) or anaplastic lymphoma kinase (ALK) inhibitor in all patients with advanced-stage adenocarcinoma.
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Metastatic non-small-cell lung cancer (NSCLC): ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up
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Updated Molecular Testing Guideline for the Selection of Lung Cancer Patients for Treatment With Targeted Tyrosine Kinase Inhibitors: Guideline From the College of American Pathologists, the International Association for the Study of Lung Cancer, and the Association for Molecular Pathology
Neal I. Lindeman,Philip T. Cagle,Dara L. Aisner,Maria E. Arcila,Mary Beth Beasley,Eric H. Bernicker,Carol Colasacco,Sanja Dacic,Fred R. Hirsch,Keith M. Kerr,David J. Kwiatkowski,Marc Ladanyi,Jan A. Nowak,Lynette M. Sholl,Robyn Temple-Smolkin,Benjamin Solomon,Lesley Souter,Erik Thunnissen,Ming-Sound Tsao,Christina B. Ventura,Murry W. Wynes,Yasushi Yatabe +21 more
TL;DR: The 2013 guideline for molecular analysis of lung cancers was largely reaffirmed with updated recommendations to allow testing of cytology samples, require improved assay sensitivity, and recommend against the use of immunohistochemistry for EGFR testing.
References
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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
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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