Journal ArticleDOI
EGFR exon 20 insertion mutations in non-small-cell lung cancer: preclinical data and clinical implications
TLDR
In this paper, the structural, molecular, and clinical implications of EGFR exon 20 insertions were reviewed and an update with an emphasis on the structural and molecular implications of these insertions was provided.Abstract:
Summary Lung cancer is the leading cause of cancer-related death. The identification of epidermal growth factor receptor (EGFR) somatic mutations defined a new, molecularly classified subgroup of non-small-cell lung cancer (NSCLC). Classic EGFR activating mutations, such as inframe deletions in exon 19 or the Leu858Arg (L858R) point mutation in exon 21 are associated with sensitivity to first generation quinazoline reversible EGFR tyrosine kinase inhibitors (TKIs). EGFR exon 20 insertion mutations, which are typically located after the C-helix of the tyrosine kinase domain of EGFR, may account for up to 4% of all EGFR mutations. Preclinical models have shown that the most prevalent EGFR exon 20 insertion mutated proteins are resistant to clinically achievable doses of reversible (gefitinib, erlotinib) and irreversible (neratinib, afatinib, PF00299804) EGFR TKIs. Growing clinical experience with patients whose tumours harbour EGFR exon 20 insertions corresponds with the preclinical data; very few patients have had responses to EGFR TKIs. Despite the prevalence and biological importance of EGFR exon 20 insertions, few reports have summarised all preclinical and clinical data on these mutations. Here, we review the literature and provide an update with an emphasis on the structural, molecular, and clinical implications of EGFR exon 20 insertions.read more
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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.
Journal ArticleDOI
Clinical activity of afatinib in patients with advanced non-small-cell lung cancer harbouring uncommon EGFR mutations: a combined post-hoc analysis of LUX-Lung 2, LUX-Lung 3, and LUX-Lung 6.
James Chih-Hsin Yang,Lecia V. Sequist,Sarayut Lucien Geater,Chun-Ming Tsai,Tony Mok,Martin Schuler,Nobuyuki Yamamoto,Chong-Jen Yu,Sai-Hong Ignatius Ou,Caicun Zhou,Dan Massey,Victoria Zazulina,Yi-Long Wu +12 more
TL;DR: Afatinib was active in non-small-cell lung cancer tumours that harboured certain types of uncommon EGFR mutations, especially Gly719Xaa, Leu861Gln, and Ser768Ile, but less active in other mutations types.
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 lung cancer.
Journal ArticleDOI
Featured Updates to the NCCN Guidelines
Robert J. Motzer,Eric Jonasch,M. Dror Michaelson,Lakshminarayanan Nandagopal,John L. Gore,Saby George,Ajjai Alva,Naomi B. Haas,Michael R. Harrison,Elizabeth R. Plimack,Jeffrey A. Sosman,Neeraj Agarwal,Sam B. Bhayani,Toni K. Choueiri,Brian A. Costello,Ithaar Derweesh,Thomas H. Gallagher,Steven L. Hancock,Christos Kyriakopoulos,Chad A. LaGrange,Elaine T. Lam,Clayton Lau,Bryan Lewis,Brandon Manley,Brittany McCreery,Andrew McDonald,Amir Mortazavi,Phillip M. Pierorazio,Lee Ponsky,Bruce G. Redman,Bradley G. Somer,Geoffrey Wile,Mary A. Dwyer,Lydia J. Hammond,Griselda Zuccarino-Catania +34 more
TL;DR: The major changes to the 2012 and 2011 NCCN Guidelines for Soft Tissue Sarcoma pertain to the management of patients with gastrointestinal stromal tumors and desmoid tumors.
Journal ArticleDOI
Prospective Comprehensive Molecular Characterization of Lung Adenocarcinomas for Efficient Patient Matching to Approved and Emerging Therapies.
Emmet Jordan,Hyunjae R. Kim,Maria E. Arcila,David Barron,Debyani Chakravarty,Jianjiong Gao,Matthew T. Chang,Andy Ni,Ritika Kundra,Philip Jonsson,Gowtham Jayakumaran,Sizhi Paul Gao,Hannah C. Johnsen,Aphrothiti J. Hanrahan,Ahmet Zehir,Natasha Rekhtman,Michelle S. Ginsberg,Bob T. Li,Helena A. Yu,Paul K. Paik,Alexander Drilon,Matthew D. Hellmann,Dalicia N. Reales,Ryma Benayed,Valerie W. Rusch,Mark G. Kris,Jamie E. Chaft,José Baselga,Barry S. Taylor,Nikolaus Schultz,Charles M. Rudin,David M. Hyman,Michael F. Berger,David B. Solit,Marc Ladanyi,Gregory J. Riely +35 more
TL;DR: The data reported here suggest that broader, early testing for molecular alterations that have not yet been recognized as standard-of-care predictive biomarkers of drug response could accelerate the development of targeted agents for rare mutational events and could result in improved clinical outcomes.
References
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Journal ArticleDOI
Global cancer statistics
TL;DR: A substantial proportion of the worldwide burden of cancer could be prevented through the application of existing cancer control knowledge and by implementing programs for tobacco control, vaccination, and early detection and treatment, as well as public health campaigns promoting physical activity and a healthier dietary intake.
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
TL;DR: A subgroup of patients with non-small-cell lung cancer have specific mutations in the EGFR gene which correlate with clinical responsiveness to the tyrosine kinase inhibitor gefitinib, and these mutations lead to increased growth factor signaling and confer susceptibility to the inhibitor.
Journal ArticleDOI
EGFR mutations in lung cancer: correlation with clinical response to gefitinib therapy.
J. Guillermo Paez,Pasi A. Jänne,Pasi A. Jänne,Jeffrey C. Lee,Sean Tracy,Heidi Greulich,Heidi Greulich,Stacey Gabriel,Paula Herman,Frederic J. Kaye,Neal I. Lindeman,Titus J. Boggon,Katsuhiko Naoki,Hidefumini Sasaki,Yoshitaka Fujii,Michael J. Eck,William R. Sellers,William R. Sellers,William R. Sellers,Bruce E. Johnson,Bruce E. Johnson,Matthew Meyerson,Matthew Meyerson +22 more
TL;DR: Results suggest that EGFR mutations may predict sensitivity to gefitinib, and treatment with the EGFR kinase inhibitor gefitsinib causes tumor regression in some patients with NSCLC, more frequently in Japan.
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
Gefitinib or Chemotherapy for Non–Small-Cell Lung Cancer with Mutated EGFR
Makoto Maemondo,Akira Inoue,Kunihiko Kobayashi,Shunichi Sugawara,Satoshi Oizumi,Hiroshi Isobe,Akihiko Gemma,Masao Harada,Hirohisa Yoshizawa,Ichiro Kinoshita,Yuka Fujita,Shoji Okinaga,Haruto Hirano,Kozo Yoshimori,Toshiyuki Harada,Takashi Ogura,Masahiro Ando,Hitoshi Miyazawa,Tomoaki Tanaka,Yasuo Saijo,Koichi Hagiwara,Satoshi Morita,Toshihiro Nukiwa +22 more
TL;DR: First-line gefitinib for patients with advanced non-small-cell lung cancer who were selected on the basis of EGFR mutations improved progression-free survival, with acceptable toxicity, as compared with standard chemotherapy.
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