Journal ArticleDOI
Dabrafenib and trametinib versus dabrafenib and placebo for Val600 BRAF-mutant melanoma: a multicentre, double-blind, phase 3 randomised controlled trial
Georgina V. Long,Georgina V. Long,Daniil Stroyakovskiy,Helen Gogas,Evgeny Levchenko,Filippo de Braud,James Larkin,Claus Garbe,Thomas Jouary,Axel Hauschild,Jean-Jacques Grob,Vanna Chiarion-Sileni,Céleste Lebbé,Mario Mandalà,Michael Millward,Ana Arance,Igor Bondarenko,John B. A. G. Haanen,Johan Hansson,Jochen Utikal,Jochen Utikal,Virginia Ferraresi,Nadezhda Kovalenko,Peter Mohr,Volodymr Probachai,Dirk Schadendorf,Paul Nathan,Caroline Robert,Caroline Robert,Antoni Ribas,Douglas J Demarini,Jhangir G. Irani,Suzanne Swann,Jeffrey J. Legos,Fan Jin,Bijoyesh Mookerjee,Keith T. Flaherty +36 more
TLDR
The improvement in overall survival establishes the combination of dabrafenib and trametinib as the standard targeted treatment for BRAF Val600 mutation-positive melanoma.About:
This article is published in The Lancet.The article was published on 2015-08-01. It has received 1099 citations till now. The article focuses on the topics: Dabrafenib & Trametinib.read more
Citations
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Distinct clinical patterns and immune infiltrates are observed at time of progression on targeted therapy versus immune checkpoint blockade for melanoma
Zachary A. Cooper,Alexandre Reuben,Christine N. Spencer,Peter A. Prieto,Jacob Austin-Breneman,Hong Jiang,Cara Haymaker,Vancheswaran Gopalakrishnan,Michael T. Tetzlaff,Dennie T. Frederick,Ryan J. Sullivan,Rodabe N. Amaria,Sapna Pradyuman Patel,Patrick Hwu,Scott E. Woodman,Isabella C. Glitza,Adi Diab,Luis M Vence,Jaime Rodriguez-Canales,Edwin R. Parra,Ignacio I. Wistuba,Lisa M. Coussens,Arlene H. Sharpe,Keith T. Flaherty,Jeffrey E. Gershenwald,Lynda Chin,Michael A. Davies,Karen Clise-Dwyer,James P. Allison,Padmanee Sharma,Jennifer A. Wargo +30 more
TL;DR: It is suggested that antitumor immune responses should be assessed when considering therapeutic options for patients with melanoma after major advances in the treatment of melanoma through the use of targeted therapy and immune checkpoint blockade.
Journal ArticleDOI
Vertical inhibition of the PI3K/Akt/mTOR pathway is synergistic in breast cancer.
TL;DR: The data suggest that a combination of Akt and mTOR inhibitors have greater antitumor activity in breast cancer cells, which may be a viable approach to treat patients.
Journal ArticleDOI
Identification of the Serine Biosynthesis Pathway as a Critical Component of BRAF Inhibitor Resistance of Melanoma, Pancreatic, and Non–Small Cell Lung Cancer Cells
Kayleigh C. Ross,Andrew J. Andrews,Christopher D. Marion,Timothy J. Yen,Vikram Bhattacharjee +4 more
TL;DR: The novel aspects of this study are the direct identification of serine biosynthesis as a critical mechanism of BRAF V600E inhibitor resistance and the first successful example of using gemcitabine + BRAFis in combination to kill previously drug-resistant cancer cells.
Journal ArticleDOI
Dabrafenib in combination with trametinib in the treatment of patients with BRAF V600-positive advanced or metastatic non-small cell lung cancer: clinical evidence and experience.
TL;DR: Preclinical and clinical data for BRAF and MEK inhibitor combination treatment for NSCLC patients with BRAF V600E mutation are outlined.
Journal ArticleDOI
Acquired Resistance to Clinical Cancer Therapy: A Twist in Physiological Signaling
Andreas Wicki,Mario Mandalà,Daniela Massi,Daniela Taverna,Huifang Tang,Brian A. Hemmings,Gongda Xue +6 more
TL;DR: The molecular mechanisms of how conventional physiological signal transduction confers to acquired drug resistance in cancer patients are discussed, particularly on protooncogenic receptor kinase inhibition-elicited tumor cell adaptation through two major core downstream signaling cascades, the PI3K/Akt and MAPK pathways.
References
More filters
Journal ArticleDOI
New response evaluation criteria in solid tumours: Revised RECIST guideline (version 1.1)
Elizabeth Eisenhauer,P. Therasse,Jan Bogaerts,Lawrence H. Schwartz,Daniel J. Sargent,Robert Ford,Janet Dancey,S. Arbuck,S. Gwyther,Margaret M. Mooney,Larry Rubinstein,Lalitha K. Shankar,Lori E. Dodd,Robert M. Kaplan,Denis Lacombe,Jaap Verweij +15 more
TL;DR: The revised RECIST includes a new imaging appendix with updated recommendations on the optimal anatomical assessment of lesions, and a section on detection of new lesions, including the interpretation of FDG-PET scan assessment is included.
Journal ArticleDOI
Improved Survival with Ipilimumab in Patients with Metastatic Melanoma.
F. Stephen Hodi,Steven J. O'Day,David F. McDermott,R. W. Weber,Jeffrey A. Sosman,John B. A. G. Haanen,Rene Gonzalez,Caroline Robert,Dirk Schadendorf,Jessica C. Hassel,Wallace Akerley,Alfons J.M. van den Eertwegh,Jose Lutzky,Paul Lorigan,Julia Vaubel,Gerald P. Linette,David W. Hogg,Christian H. Ottensmeier,Céleste Lebbé,Christian Peschel,Ian Quirt,Joseph I. Clark,Jedd D. Wolchok,Jeffrey S. Weber,Jason Tian,Michael Yellin,Geoffrey M. Nichol,Axel Hoos,Walter J. Urba +28 more
TL;DR: Ipilimumab, with or without a gp100 peptide vaccine, as compared with gp100 alone, improved overall survival in patients with previously treated metastatic melanoma.
Journal ArticleDOI
Pembrolizumab versus Ipilimumab in Advanced Melanoma
Caroline Robert,Caroline Robert,Caroline Robert,Jacob Schachter,Georgina V. Long,Ana Arance,Jean-Jacques Grob,Laurent Mortier,Laurent Mortier,Adil Daud,Matteo S. Carlino,Catriona M. McNeil,Michal Lotem,James Larkin,Paul Lorigan,Bart Neyns,Christian U. Blank,Omid Hamid,Christine Mateus,Christine Mateus,Ronnie Shapira-Frommer,Ronnie Shapira-Frommer,Michele Kosh,Honghong Zhou,Nageatte Ibrahim,Scot Ebbinghaus,Antoni Ribas +26 more
TL;DR: The anti-PD-1 antibody pembrolizumab prolonged progression-free survival and overall survival and had less high-grade toxicity than did ipilimumab in patients with advanced melanoma.
Journal ArticleDOI
Nivolumab in previously untreated melanoma without BRAF mutation.
Caroline Robert,Georgina V. Long,Benjamin Brady,Caroline Dutriaux,Michele Maio,Laurent Mortier,Jessica C. Hassel,Piotr Rutkowski,Catriona M. McNeil,Ewa Kalinka-Warzocha,Kerry J. Savage,Micaela Hernberg,Céleste Lebbé,Julie Charles,Catalin Mihalcioiu,Vanna Chiarion-Sileni,Cornelia Mauch,Francesco Cognetti,Ana Arance,Henrik Schmidt,Dirk Schadendorf,Helen Gogas,Lotta Lundgren-Eriksson,Christine Horak,Brian Sharkey,Ian M. Waxman,Victoria Atkinson,Paolo A. Ascierto,Abstr Act +28 more
TL;DR: Nivolumab was associated with significant improvements in overall survival and progression-free survival, as compared with dacarbazine, among previously untreated patients who had metastatic melanoma without a BRAF mutation.
Journal ArticleDOI
A multiple testing procedure for clinical trials.
TL;DR: The overall size of the procedure is shown to be controlled with virtually the same accuracy as the single sample chi-square test based on N(m1 + m2) observations and the power is found to bevirtually the same.
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