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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Journal ArticleDOI
The Role of Autophagy in the Resistance to BRAF Inhibition in BRAF-Mutated Melanoma.
TL;DR: How Autophagy is up-regulated by BRAF inhibitors, and how autophagy induces the resistance to these agents is discussed.
Journal ArticleDOI
Dabrafenib plus trametinib is effective in the treatment of BRAF V600-mutated metastatic melanoma patients: analysis of patients from the dabrafenib plus trametinib Named Patient Program (DESCRIBE II).
Victoria Atkinson,Shahneen Sandhu,Geke A. P. Hospers,Georgina V. Long,Massimo Aglietta,Pier Francesco Ferrucci,Skaiste Tulyte,Gian Carlo Antonini Cappellini,Virtudes Soriano,Sayed Ali,Alexandr Poprach,Alvydas Česas,Delvys Rodriguez-Abreu,Mike Lau,Egbert de Jong,Philippe Legenne,Dara Stein,Brianna King,Johannes V. Van Thienen +18 more
TL;DR: Dabrafenib plus trametinib showed substantial clinical activity in NPP patients with BRAF V600-mutated unresectable or metastatic melanoma and across lines of therapy with a well tolerated and manageable safety profile.
Journal ArticleDOI
Immunotherapy Potentiates the Effect of Chemotherapy in Metastatic Melanoma-A Retrospective Study.
Reut Hadash-Bengad,Emma Hajaj,Shiri Klein,Sharon Merims,Stephen Frank,Galit Eisenberg,Alexander Yakobson,Marina Orevi,Nadia Caplan,Tamar Peretz,Michal Lotem,Jonatan E. Cohen,Jonatan E. Cohen +12 more
TL;DR: A retrospective study to compare the efficacy of chemotherapy given with prior immunotherapy, to its efficacy given without it, and showed an increased proportion of CD8+ cells, with elevated PD-1 and CD69 expression, while on chemotherapy, as compared with all-time points on ICIs, suggesting immune-activation.
Journal ArticleDOI
The adjuvant treatment revolution for high-risk melanoma patients.
TL;DR: The past 5 years have witnessed the results of many practice-changing studies that have dramatically improved the landscape of adjuvant therapy in patients with resected, high-risk melanoma, with a view on future perspectives.
Journal ArticleDOI
Surveillance imaging for metastasis in high-risk melanoma: importance in individualized patient care and survivorship.
Morganna Freeman,Shachar Laks +1 more
TL;DR: A recent review as discussed by the authors discusses published evidence on surveillance imaging to detect metastasis in high-risk melanoma, the need for early recurrence detection and implications for value-based clinical decision-making, survivorship care and multidisciplinary patient management.
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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