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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A Phase I Study of LY3009120, a Pan-RAF Inhibitor, in Patients with Advanced or Metastatic Cancer.
Ryan J. Sullivan,Antoine Hollebecque,Keith T. Flaherty,Geoffrey I. Shapiro,Jordi Rodon Ahnert,Michael Millward,Wei Zhang,Ling Gao,Amanda K. Sykes,Melinda D. Willard,Danni Yu,Andrew E. Schade,KrisAnne J Crowe,Daniel L. Flynn,Michael Kaufman,Henry James Robert,Sheng-Bin Peng,Karim A. Benhadji,Ilaria Conti,Michael S. Gordon,Ramon V. Tiu,David S. Hong +21 more
TL;DR: This multicenter, open-label, phase I clinical trial consisted of part A (dose escalation) and part B (dose confirmation) in patients with advanced/metastatic cancer to identify a recommended phase II dose (RP2D).
Journal ArticleDOI
First experience and clinical results using a new non-coplanar mono-isocenter technique (HyperArc™) for Linac-based VMAT radiosurgery in brain metastases
Filippo Alongi,Alba Fiorentino,Fabiana Gregucci,Stefanie Corradini,Niccolò Giaj-Levra,Luigi Romano,Michele Rigo,Francesco Ricchetti,Alberto Beltramello,Gianluigi Lunardi,Rosario Mazzola,Ruggero Ruggieri +11 more
TL;DR: The present first clinical data show that SFRT/SRS with HyperArc™ is safe and effective for BMs patients and should be further explored in randomized trials.
Journal ArticleDOI
Principles of Targeted Therapy for Melanoma.
TL;DR: An overview of the MAPK pathway as well as the other major pathways implicated in melanoma development is presented, and activating KIT mutations are rarely found to cause melanomas and may provide an actionable target for therapy.
Journal ArticleDOI
Randomized Phase III Trial Evaluating Spartalizumab Plus Dabrafenib and Trametinib for BRAF V600–Mutant Unresectable or Metastatic Melanoma
Reinhard Dummer,Georgina V. Long,Caroline Robert,Hussein Abdul-Hassan Tawbi,Keith T. Flaherty,Paolo A. Ascierto,Paul Nathan,Piotr Rutkowski,O. Leonov,Caroline Dutriaux,Mario Mandalà,Paul Lorigan,Pier Francesco Ferrucci,Jean-Jacques Grob,Nicolas Meyer,Helen Gogas,Daniil Stroyakovskiy,Ana Arance,Jan C. Brase,S. Green,Tomas Haas,Aisha Masood,Eduard Gasal,Antoni Ribas,Dirk Schadendorf +24 more
TL;DR: The study did not meet its primary end point; broad first-line use of sparta-DabTram is not supported by these results; further biomarker-driven investigation may identify patient subpopulations who could benefit from checkpoint inhibitor plus targeted therapy combinations.
Journal ArticleDOI
18F-FDG PET/CT longitudinal studies in patients with advanced metastatic melanoma for response evaluation of combination treatment with vemurafenib and ipilimumab.
Christos Sachpekidis,Annette Kopp-Schneider,Lara Elena Hakim-Meibodi,Antonia Dimitrakopoulou-Strauss,Jessica C. Hassel +4 more
TL;DR: 16 BRAF-mutation positive, metastatic melanoma patients with highly advanced disease received combination therapy of vemurafenib and ipilimumab as an individual treatment decision to assess the role of fluorine-18-fluorodeoxyglucose PET/computed tomography (PET/CT) in the evaluation of the clinical benefit (CB) of this combination treatment.
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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