Dabrafenib plus trametinib versus dabrafenib monotherapy in patients with metastatic BRAF V600E/K-mutant melanoma: long-term survival and safety analysis of a phase 3 study.
Georgina V. Long,Keith T. Flaherty,Daniil Stroyakovskiy,Helen Gogas,Evgeny Levchenko,F. de Braud,James Larkin,Claus Garbe,Thomas Jouary,Axel Hauschild,Vanna Chiarion-Sileni,Céleste Lebbé,Mario Mandalà,Michael Millward,Ana Arance,Igor Bondarenko,J.B.A.G. Haanen,Johan Hansson,Jochen Utikal,Virginia Ferraresi,Peter Mohr,V. Probachai,Dirk Schadendorf,Paul Nathan,Caroline Robert,Antoni Ribas,Michael A. Davies,Stephen R. Lane,Jeffrey J. Legos,Bijoyesh Mookerjee,J.-J. Grob +30 more
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TLDR
It is demonstrated that durable (≥3 years) survival is achievable with dabrafenib plus trametinib in patients with BRAF V600-mutant metastatic melanoma and support long-term first-line use of the combination in this setting.About:
This article is published in Annals of Oncology.The article was published on 2017-07-01 and is currently open access. It has received 483 citations till now. The article focuses on the topics: Dabrafenib & Trametinib.read more
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Updates in adjuvant systemic therapy for melanoma
Minyoung Kwak,Norma E. Farrow,April K.S. Salama,Paul J. Mosca,Brent A. Hanks,Craig L. Slingluff,Georgia M. Beasley +6 more
TL;DR: Current indications for adjuvant therapy, which currently includes a heterogenous group of stages III and IV patients with melanoma, are reviewed and the evidence for selecting the most appropriate treatment regimen for the individual patient is discussed.
Journal ArticleDOI
Drugging the Undruggable: Advances on RAS Targeting in Cancer.
TL;DR: In this paper, the authors discuss historical efforts to target RAS directly and approaches to target effector signalling, including combinations that overcome limitations of single-agent targeting, and briefly discuss novel approaches to targeting non-G12C mutant isoforms.
Journal ArticleDOI
Metastatic Melanoma: Recent Therapeutic Progress and Future Perspectives.
N. Malissen,Jean-Jacques Grob +1 more
TL;DR: The main goal is to avoid or circumvent primary or secondary immune resistance to anti- PD-1 therapy not only by targeting other players in the tumor microenvironment but also by optimizing treatment sequencing and combining anti-PD-1 with other treatments, especially with BRAF and MEK inhibitors.
Journal ArticleDOI
Current and emerging systemic therapies for cutaneous metastatic melanoma.
TL;DR: There is need for instructive biomarker assessment to identify patients likely to respond or be refractory to current therapies, to identify mechanisms of resistance and to direct further treatment options to patients based on individual disease biology.
Journal ArticleDOI
Molecular Markers and Targets in Melanoma.
TL;DR: In this article, the authors describe the current knowledge of molecular pathways and discuss current and potential therapeutic targets in melanoma, focusing on their clinical relevance of development, and discuss their clinical significance.
References
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Journal ArticleDOI
Combined BRAF and MEK Inhibition in Melanoma with BRAF V600 Mutations
Keith T. Flaherty,J. R. Infante,Adil Daud,Rene Gonzalez,Richard F. Kefford,Jeffrey A. Sosman,Omid Hamid,Lynn M. Schuchter,Jonathan Cebon,Nageatte Ibrahim,Ragini Kudchadkar,Howard A. Burris,Gerald S. Falchook,Alain Algazi,Karl D. Lewis,Georgina V. Long,Igor Puzanov,Peter F. Lebowitz,Ajay Singh,Shonda M Little,Peng Sun,Alicia Allred,Daniele Ouellet,Kevin B. Kim,Kiran Patel,Jeffrey S. Weber +25 more
TL;DR: Dabrafenib and trametinib were safely combined at full monotherapy doses, and the rate of pyrexia was increased with combination therapy, whereas the rates of proliferative skin lesions was nonsignificantly reduced.
Journal ArticleDOI
Nivolumab versus chemotherapy in patients with advanced melanoma who progressed after anti-CTLA-4 treatment (CheckMate 037): a randomised, controlled, open-label, phase 3 trial.
Jeffrey S. Weber,Sandra P. D'Angelo,David R. Minor,F. Stephen Hodi,Ralf Gutzmer,Bart Neyns,Christoph Hoeller,Nikhil I. Khushalani,Wilson H. Miller,Christopher D. Lao,Gerald P. Linette,Luc Thomas,Paul Lorigan,Kenneth F. Grossmann,Jessica C. Hassel,Michele Maio,Mario Sznol,Paolo A. Ascierto,Peter Mohr,Bartosz Chmielowski,Alan H. Bryce,Inge Marie Svane,Jean-Jacques Grob,Angela M. Krackhardt,Christine Horak,Alexandre Lambert,Arvin Yang,James Larkin +27 more
TL;DR: Nivolumab led to a greater proportion of patients achieving an objective response and fewer toxic effects than with alternative available chemotherapy regimens for patients with advanced melanoma that has progressed after ipilimumab or ipilicumab and a BRAF inhibitor.
Journal ArticleDOI
Improved Overall Survival in Melanoma with Combined Dabrafenib and Trametinib
Caroline Robert,Boguslawa Karaszewska,Jacob Schachter,Piotr Rutkowski,Andrzej Mackiewicz,Daniil Stroiakovski,Michael Lichinitser,Reinhard Dummer,Florent Grange,Laurent Mortier,Vanna Chiarion-Sileni,Kamil Drucis,Ivana Krajsová,Axel Hauschild,Paul Lorigan,Pascal Wolter,Georgina V. Long,Keith T. Flaherty,Paul Nathan,Antoni Ribas,Antoni Ribas,Anne-Marie Martin,Peng Sun,Wendy A. Crist,Jeff Legos,Stephen D. Rubin,Shonda M Little,Dirk Schadendorf +27 more
TL;DR: Dabrafenib plus trametinib, as compared with vemurafenib monotherapy, significantly improved overall survival in previously untreated patients with metastatic melanoma with BRAF V600E or V600K mutations, without increased overall toxicity.
Journal ArticleDOI
Pooled Analysis of Long-Term Survival Data From Phase II and Phase III Trials of Ipilimumab in Unresectable or Metastatic Melanoma
Dirk Schadendorf,F. Stephen Hodi,Caroline Robert,Jeffrey S. Weber,Kim Margolin,Omid Hamid,Debra A. Patt,Tai-Tsang Chen,David Berman,Jedd D. Wolchok +9 more
TL;DR: A plateau in the survival curve was observed, beginning at approximately 3 years, which was independent of prior therapy or ipilimumab dose, and added to the evidence supporting the durability of long-term survival in ipILimumab-treated patients with advanced melanoma.
Journal ArticleDOI
Combined BRAF and MEK Inhibition versus BRAF Inhibition Alone in Melanoma
Georgina V. Long,Daniil Stroyakovskiy,Helen Gogas,Evgeny Levchenko,F. de Braud,James Larkin,Claus Garbe,T. Jouary,Axel Hauschild,Jean-Jacques Grob,V. Chiarion Sileni,Céleste Lebbé,Mario Mandalà,Michael Millward,Ana Arance,Igor Bondarenko,John B. A. G. Haanen,Johan Hansson,Jochen Utikal,Virginia Ferraresi,Nadezhda Kovalenko,Peter Mohr,V. Probachai,Dirk Schadendorf,Paul Nathan,Caroline Robert,Antoni Ribas,Douglas J. DeMarini,Jhangir G. Irani,Michelle Casey,Daniele Ouellet,Anne-Marie Martin,Ngocdiep T. Le,Kiran Patel,Keith T. Flaherty +34 more
TL;DR: A combination of dabraenib and trametinib, as compared with dabrafenib alone, improved the rate of progression-free survival in previously untreated patients who had metastatic melanoma with BRAF V600E or V600K mutations.
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