KRAS Mutation Is an Important Predictor of Resistance to Therapy with Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors in Non–Small-Cell Lung Cancer
Erminia Massarelli,Marileila Varella-Garcia,Ximing Tang,Ana Carolina Xavier,Natalie C. Ozburn,Diane D. Liu,Benjamin N. Bekele,Roy S. Herbst,Ignacio I. Wistuba +8 more
TLDR
KRAS mutation should be included as indicator of resistance in the panel of markers used to predict response to EGFR-TKIs in NSCLC.Abstract:
Purpose: EGFR gene mutations and increased EGFR copy number have been associated with favorable response to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (EGFR-TKI) in patients with non–small-cell lung cancer (NSCLC). In contrast, KRAS mutation has been shown to predict poor response to such therapy. We tested the utility of combinations of these three markers in predicting response and survival in patients with NSCLC treated with EGFR-TKIs. Experimental Design: Patients with advanced NSCLC treated with EGFR-TKI with available archival tissue specimens were included. EGFR and KRAS mutations were analyzed using PCR-based sequencing. EGFR copy number was analyzed using fluorescence in situ hybridization. Results: The study included 73 patients, 59 of whom had all three potential markers successfully analyzed. EGFR mutation was detected in 7 of 71 patients (9.8%), increased EGFR copy number in 32 of 59 (54.2%), and KRAS mutation in 16 of 70 (22.8%). EGFR mutation ( P EGFR copy number ( P = 0.48) correlated with favorable response. No survival benefit was detected in patients with either of these features. KRAS mutation correlated with progressive disease ( P = 0.04) and shorter median time to progression ( P = 0.0025) but not with survival. Patients with both EGFR mutation and increased EGFR copy number had a >99.7% chance of objective response, whereas patients with KRAS mutation with or without increased EGFR copy number had a >96.5% chance of disease progression. Conclusion: KRAS mutation should be included as indicator of resistance in the panel of markers used to predict response to EGFR-TKIs in NSCLC.read more
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K-ras mutations and benefit from cetuximab in advanced colorectal cancer.
Christos S. Karapetis,Shirin Khambata-Ford,Derek J. Jonker,Christopher J. O'Callaghan,Dongsheng Tu,Niall C. Tebbutt,R. John Simes,Haji Chalchal,Jeremy Shapiro,Sonia Robitaille,Timothy J. Price,Lois E. Shepherd,Heather-Jane Au,Christiane Langer,Malcolm J. Moore,John Zalcberg +15 more
TL;DR: Patients with a colorectal tumor bearing mutated K-ras did not benefit from cetuximab, whereas patients with a tumor bearing wild-type K-ra did benefit fromcetuxIMab.
Journal ArticleDOI
Wild-type KRAS is required for panitumumab efficacy in patients with metastatic colorectal cancer
Rafael G. Amado,Michael S. Wolf,Marc Peeters,Eric Van Cutsem,Salvatore Siena,Daniel J. Freeman,Todd Juan,Robert Sikorski,Sid Suggs,Robert Radinsky,Scott D. Patterson,David D. Chang +11 more
TL;DR: Panitumumab monotherapy efficacy in mCRC is confined to patients with WT KRAS tumors, and KRAS status should be considered in selecting patients withmCRC as candidates for panitumuab mon Therapy.
Journal ArticleDOI
EGFR Antagonists in Cancer Treatment
TL;DR: The mechanisms of action of EGFR inhibitors, their anticancer activity, and clinical issues concerning their use in the treatment of patients with cancer are discussed.
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.
Journal ArticleDOI
KRASG12C Inhibition with Sotorasib in Advanced Solid Tumors.
David S. Hong,Marwan Fakih,John H. Strickler,Jayesh Desai,G. Durm,Geoffrey I. Shapiro,Gerald S. Falchook,Timothy J. Price,Adrian G. Sacher,Crystal S. Denlinger,Yung-Jue Bang,Grace K. Dy,John C. Krauss,Yasutoshi Kuboki,James Kuo,Andrew L. Coveler,Keunchil Park,Tae Won Kim,Fabrice Barlesi,Pamela N. Munster,Suresh S. Ramalingam,Timothy F. Burns,Funda Meric-Bernstam,H. Henary,J. Ngang,Gataree Ngarmchamnanrith,J. Kim,Brett E. Houk,Jude Canon,J. Russell Lipford,Gregory Friberg,Piro Lito,Ramaswamy Govindan,Bob T. Li +33 more
TL;DR: Sotorasib showed encouraging anticancer activity in patients with heavily pretreated advanced solid tumors harboring the KRAS p.G12C mutation and responded to pharmacokinetics and objective response according to Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1.
References
More filters
Journal ArticleDOI
New Guidelines to Evaluate the Response to Treatment in Solid Tumors
Patrick Therasse,Susan G. Arbuck,Elizabeth Eisenhauer,Jantien Wanders,Richard Kaplan,Larry Rubinstein,Jaap Verweij,Martine Van Glabbeke,Allan T. van Oosterom,Michaele C. Christian,S. Gwyther +10 more
TL;DR: A model by which a combined assessment of all existing lesions, characterized by target lesions and nontarget lesions, is used to extrapolate an overall response to treatment is proposed, which is largely validated by the Response Evaluation Criteria in Solid Tumors Group and integrated into the present guidelines.
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
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
Cancer statistics, 2006.
Ahmedin Jemal,Rebecca L. Siegel,Elizabeth Ward,Taylor Murray,Jiaquan Xu,Carol Smigal,Michael J. Thun +6 more
TL;DR: The American Cancer Society estimated the number of new cancer cases and deaths expected in the United States in the current year and compiles the most recent data on cancer incidence, mortality, and survival based on incidence data from the National Cancer Institute and mortality data from National Center for Health Statistics as discussed by the authors.
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