Journal ArticleDOI
Panitumumab-FOLFOX4 treatment and RAS mutations in colorectal cancer
Jean-Yves Douillard,Kelly S. Oliner,Salvatore Siena,Josep Tabernero,Ronald Burkes,Mario Edmundo Barugel,Yves Humblet,György Bodoky,David Cunningham,Jacek Jassem,Fernando Rivera,Ilona Kocáková,Paul Ruff,Maria Blasinska-Morawiec,Martin Šmakal,Jean-Luc Canon,Mark Rother,Richard Thomas Williams,Alan Rong,Jeffrey Wiezorek,Roger Sidhu,Scott D. Patterson +21 more
TLDR
Additional RAS mutations predicted a lack of response in patients who received panitumumab-FOLFOX4 treatment, which was consistent with the findings in patients with KRAS mutations in exon 2.Abstract:
BACKGROUND: Patients with metastatic colorectal cancer that harbors KRAS mutations in exon 2 do not benefit from anti-epidermal growth factor receptor (EGFR) therapy. Other activating RAS mutations may also be negative predictive biomarkers for anti-EGFR therapy. METHODS: In this prospective-retrospective analysis, we assessed the efficacy and safety of panitumumab plus oxaliplatin, fluorouracil, and leucovorin (FOLFOX4) as compared with FOLFOX4 alone, according to RAS (KRAS or NRAS) or BRAF mutation status. A total of 639 patients who had metastatic colorectal cancer without KRAS mutations in exon 2 had results for at least one of the following: KRAS exon 3 or 4; NRAS exon 2, 3, or 4; or BRAF exon 15. The overall rate of ascertainment of RAS status was 90%. RESULTS: Among 512 patients without RAS mutations, progression-free survival was 10.1 months with panitumumab-FOLFOX4 versus 7.9 months with FOLFOX4 alone (hazard ratio for progression or death with combination therapy, 0.72; 95% confidence interval [CI], 0.58 to 0.90; P = 0.004). Overall survival was 26.0 months in the panitumumab-FOLFOX4 group versus 20.2 months in the FOLFOX4-alone group (hazard ratio for death, 0.78; 95% CI, 0.62 to 0.99; P = 0.04). A total of 108 patients (17%) with non-mutated KRAS exon 2 had other RAS mutations. These mutations were associated with inferior progression-free survival and overall survival with panitumumab-FOLFOX4 treatment, which was consistent with the findings in patients with KRAS mutations in exon 2. BRAF mutations were a negative prognostic factor. No new safety signals were identified. CONCLUSIONS: Additional RAS mutations predicted a lack of response in patients who received panitumumab-FOLFOX4. In patients who had metastatic colorectal cancer without RAS mutations, improvements in overall survival were observed with panitumumab-FOLFOX4 therapyread 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
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
Clinical practice guidelines in oncology
William J. Gradishar,Benjamin O. Anderson,Ron Balassanian,Sarah L. Blair,Harold J. Burstein,Amy E. Cyr,Anthony D. Elias,William B. Farrar,Andres Forero,Sharon H. Giordano,Matthew P. Goetz,Lori J. Goldstein,Steven J. Isakoff,Janice A. Lyons,P. Kelly Marcom,Ingrid A. Mayer,Beryl McCormick,Meena S. Moran,Ruth O'Regan,Sameer A. Patel,Lori J. Pierce,Elizabeth C. Reed,Kilian E. Salerno,Lee S. Schwartzberg,Amy Sitapati,Karen L. Smith,Mary Lou Smith,Hatem Soliman,George Somlo,Melinda L. Telli,John H. Ward,Rashmi Kumar,Dorothy A. Shead +32 more
TL;DR: This manuscript focuses on the NCCN Guidelines Panel recommendations for the workup, primary treatment, risk reduction strategies, and surveillance specific to DCIS.
Journal ArticleDOI
FOLFIRI plus cetuximab versus FOLFIRI plus bevacizumab as first-line treatment for patients with metastatic colorectal cancer (FIRE-3): a randomised, open-label, phase 3 trial
Volker Heinemann,Ludwig Fischer von Weikersthal,Thomas Decker,Alexander Kiani,Ursula Vehling-Kaiser,Salah-Eddin Al-Batran,Tobias Heintges,Christian A. Lerchenmuller,Christoph Kahl,G. Seipelt,Frank Kullmann,Martina Stauch,Werner Scheithauer,Jörg Hielscher,Michael Scholz,Sebastian Müller,Hartmut Link,Norbert Niederle,Andreas Rost,Heinz-Gert Höffkes,Markus Moehler,Reinhard Udo Lindig,Dominik Paul Modest,Lisa Rossius,Thomas Kirchner,Andreas Jung,Sebastian Stintzing +26 more
TL;DR: The association with longer overall survival suggests that FOLFIRI plus cetuximab could be the preferred first-line regimen for patients with KRAS exon 2 wild-type metastatic colorectal cancer.
Journal ArticleDOI
Colon Cancer, Version 1.2017, NCCN Clinical Practice Guidelines in Oncology
Al B. Benson,Alan P. Venook,Lynette Cederquist,Emily Chan,Yi-Jen Chen,Harry S. Cooper,Dustin A. Deming,Paul F. Engstrom,Peter C. Enzinger,Alessandro Fichera,Jean L. Grem,Axel Grothey,Howard S. Hochster,Sarah E. Hoffe,Steven C. Hunt,Ahmed Kamel,Natalie Kirilcuk,Smitha S. Krishnamurthi,Wells A. Messersmith,Mary F. Mulcahy,James D. Murphy,Steven J. Nurkin,Leonard B. Saltz,Sunil Sharma,David Shibata,John M. Skibber,Constantinos T. Sofocleous,Elena M. Stoffel,Eden Stotsky-Himelfarb,Christopher G. Willett,Christina Wu,Kristina M. Gregory,Deborah A. Freedman-Cass +32 more
TL;DR: This portion of the NCCN Guidelines for Colon Cancer focuses on the use of systemic therapy in metastatic disease and considers treatment history, extent of disease, goals of treatment, the efficacy and toxicity profiles of the regimens, KRAS/NRAS mutational status, and patient comorbidities and preferences.
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