Journal ArticleDOI
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
TLDR
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.Abstract:
BACKGROUND Treatment with cetuximab, a monoclonal antibody directed against the epidermal growth factor receptor, improves overall and progression-free survival and preserves the quality of life in patients with colorectal cancer that has not responded to chemotherapy. The mutation status of the K-ras gene in the tumor may affect the response to cetuximab and have treatment-independent prognostic value. METHODS We analyzed tumor samples, obtained from 394 of 572 patients (68.9%) with colo rectal cancer who were randomly assigned to receive cetuximab plus best supportive care or best supportive care alone, to look for activating mutations in exon 2 of the K-ras gene. We assessed whether the mutation status of the K-ras gene was associated with survival in the cetuximab and supportive-care groups. RESULTS Of the tumors evaluated for K-ras mutations, 42.3% had at least one mutation in exon 2 of the gene. The effectiveness of cetuximab was significantly associated with K-ras mutation status (P = 0.01 and P<0.001 for the interaction of K-ras mutation status with overall survival and progression-free survival, respectively). In patients with wild-type K-ras tumors, treatment with cetuximab as compared with supportive care alone significantly improved overall survival (median, 9.5 vs. 4.8 months; hazard ratio for death, 0.55; 95% confidence interval [CI], 0.41 to 0.74; P<0.001) and progression-free survival (median, 3.7 months vs. 1.9 months; hazard ratio for progression or death, 0.40; 95% CI, 0.30 to 0.54; P<0.001). Among patients with mutated K-ras tumors, there was no significant difference between those who were treated with cetuximab and those who received supportive care alone with respect to overall survival (hazard ratio, 0.98; P = 0.89) or progression-free survival (hazard ratio, 0.99; P = 0.96). In the group of patients receiving best supportive care alone, the mutation status of the K-ras gene was not significantly associated with overall survival (hazard ratio for death, 1.01; P = 0.97). CONCLUSIONS Patients with a colorectal tumor bearing mutated K-ras did not benefit from cetuximab, whereas patients with a tumor bearing wild-type K-ras did benefit from cetuximab. The mutation status of the K-ras gene had no influence on survival among patients treated with best supportive care alone. (ClinicalTrials.gov number, NCT00079066.)read more
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Detection of Circulating Tumor DNA in Early- and Late-Stage Human Malignancies
Chetan Bettegowda,Chetan Bettegowda,Mark Sausen,Rebecca J. Leary,Isaac Kinde,Yuxuan Wang,Nishant Agrawal,Nishant Agrawal,Bjarne Bartlett,Bjarne Bartlett,Hao Wang,Brandon Luber,Rhoda M. Alani,Emmanuel S. Antonarakis,Nilofer S. Azad,Alberto Bardelli,Henry Brem,John L. Cameron,Clarence Lee,Leslie A. Fecher,Leslie A. Fecher,Gary L. Gallia,Peter Gibbs,Dung T. Le,Dung T. Le,Robert L. Giuntoli,Michael Goggins,Michael D. Hogarty,Matthias Holdhoff,Seung-Mo Hong,Seung-Mo Hong,Yuchen Jiao,Hartmut Juhl,Jenny J. Kim,Giulia Siravegna,Daniel A. Laheru,Calogero Lauricella,Michael Lim,Evan J. Lipson,Suely Kazue Nagahashi Marie,George J. Netto,Kelly S. Oliner,Alessandro Olivi,Louise Olsson,Gregory J. Riggins,Andrea Sartore-Bianchi,Kerstin Schmidt,le-Ming Shih,Sueli Mieko Oba-Shinjo,Salvatore Siena,Dan Theodorescu,Jeanne Tie,Timothy T. Harkins,Silvio Veronese,Tian Li Wang,Jon D. Weingart,Christopher L. Wolfgang,Laura D. Wood,Dongmei Xing,Ralph H. Hruban,Jian Wu,Peter J. Allen,C. Max Schmidt,Michael A. Choti,Victor E. Velculescu,Kenneth W. Kinzler,Bert Vogelstein,Nickolas Papadopoulos,Luis A. Diaz,Luis A. Diaz +69 more
TL;DR: The ability of circulating tumor DNA (ctDNA) to detect tumors in 640 patients with various cancer types was evaluated and suggested that ctDNA is a broadly applicable, sensitive, and specific biomarker that can be used for a variety of clinical and research purposes.
Journal ArticleDOI
Cetuximab and chemotherapy as initial treatment for metastatic colorectal cancer.
Eric Van Cutsem,Claus Henning Köhne,Erika Hitre,J. Zaluski,Chung Rong Chang Chien,A. Makhson,Geert R. D'Haens,Tamás Pintér,Robert Lim,György Bodoky,Jae Kyung Roh,Gunnar Folprecht,Paul Ruff,Christopher Stroh,Sabine Tejpar,Michael Schlichting,Johannes Nippgen,Philippe Rougier +17 more
TL;DR: In this paper, the efficacy of cetuximab plus irinotecan, fluorouracil, and leucovorin (FOLFIRI) as first-line treatment for metastatic colorectal cancer was investigated.
Journal ArticleDOI
ESMO consensus guidelines for the management of patients with metastatic colorectal cancer
E. Van Cutsem,Andrés Cervantes,René Adam,Alberto Sobrero,J.H.J.M. van Krieken,Dan Aderka,E. Aranda Aguilar,Alberto Bardelli,Al B. Benson,György Bodoky,Fortunato Ciardiello,André D'Hoore,Eduardo Díaz-Rubio,J.-Y. Douillard,Michel Ducreux,Alfredo Falcone,Axel Grothey,Thomas Gruenberger,Karin Haustermans,Volker Heinemann,Paulo M. Hoff,C.-H. Köhne,R. Labianca,Pierre Laurent-Puig,Brigette B.Y. Ma,Tim Maughan,Kei Muro,Nicola Normanno,Pia Österlund,Pia Österlund,Wim J.G. Oyen,Demetris Papamichael,George Pentheroudakis,Per Pfeiffer,Timothy J. Price,C.J.A. Punt,Jens Ricke,Arnaud Roth,R. Salazar,Werner Scheithauer,H.-J. Schmoll,Josep Tabernero,Julien Taieb,Sabine Tejpar,Harpreet Wasan,Takayuki Yoshino,Aziz Zaanan,Dirk Arnold +47 more
TL;DR: These ESMO consensus guidelines have been developed based on the current available evidence to provide a series of evidence-based recommendations to assist in the treatment and management of patients with mCRC in this rapidly evolving treatment setting.
Journal ArticleDOI
Effects of KRAS, BRAF, NRAS, and PIK3CA mutations on the efficacy of cetuximab plus chemotherapy in chemotherapy-refractory metastatic colorectal cancer: a retrospective consortium analysis
Wendy De Roock,Bart Claes,David Bernasconi,Jef De Schutter,Bart Biesmans,George Fountzilas,Konstantine T. Kalogeras,Vassiliki Kotoula,Demetris Papamichael,Pierre Laurent-Puig,Frédérique Penault-Llorca,Philippe Rougier,Bruno Vincenzi,Daniele Santini,Giuseppe Tonini,Federico Cappuzzo,Milo Frattini,Francesca Molinari,Piercarlo Saletti,Sara De Dosso,Miriam Martini,Alberto Bardelli,Salvatore Siena,Andrea Sartore-Bianchi,Josep Tabernero,Teresa Macarulla,Frédéric Di Fiore,Alice Gangloff,Fortunato Ciardiello,Per Pfeiffer,Camilla Qvortrup,Tine Plato Hansen,Eric Van Cutsem,Hubert Piessevaux,Diether Lambrechts,Mauro Delorenzi,Mauro Delorenzi,Sabine Tejpar +37 more
TL;DR: This is the largest cohort to date of patients with chemotherapy-refractory metastatic colorectal cancer treated with cetuximab plus chemotherapy in the pre-KRAS selection era and confirmed that, if KRAS is not mutated, assessing BRAF, NRAS, and PIK3CA population response rates confirmed that.
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.
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