Journal ArticleDOI
Binimetinib versus dacarbazine in patients with advanced NRAS-mutant melanoma (NEMO): a multicentre, open-label, randomised, phase 3 trial
Reinhard Dummer,Dirk Schadendorf,Paolo A. Ascierto,Ana Arance,Caroline Dutriaux,Anna Maria Di Giacomo,Piotr Rutkowski,Michele Del Vecchio,Ralf Gutzmer,Mario Mandalà,Luc Thomas,Lev V. Demidov,Claus Garbe,David Hogg,Gabriella Liszkay,Paola Queirolo,Ernesto Wasserman,James Ford,Marine Weill,L. Andres Sirulnik,Valentine Jehl,Viviana Bozón,Georgina V. Long,Keith T. Flaherty +23 more
Reads0
Chats0
TLDR
Binimetinib improved progression-free survival compared with dacarbazine and was tolerable, and might represent a new treatment option for patients with NRAS-mutant melanoma after failure of immunotherapy.Abstract:
Summary Background There are no established therapies specific for NRAS -mutant melanoma despite the emergence of immunotherapy. We aimed to assess the efficacy and safety of the MEK inhibitor binimetinib versus that of dacarbazine in patients with advanced NRAS -mutant melanoma. Methods NEMO is an ongoing, randomised, open-label phase 3 study done at 118 hospitals in 26 countries. Patients with advanced, unresectable, American Joint Committee on Cancer stage IIIC or stage IV NRAS -mutant melanoma who were previously untreated or had progressed on or after previous immunotherapy were randomised (2:1) to receive either binimetinib 45 mg orally twice daily or dacarbazine 1000 mg/m 2 intravenously every 3 weeks. Randomisation was stratified by stage, performance status, and previous immunotherapy. The primary endpoint was progression-free survival assessed by blinded central review in the intention-to-treat population. Safety analyses were done in the safety population, consisting of all patients who received at least one study drug dose and one post-baseline safety assessment. This study is registered with ClinicalTrials.gov, number NCT01763164 and with EudraCT, number 2012-003593-51. Findings Between Aug 19, 2013, and April 28, 2015, 402 patients were enrolled and randomly assigned, 269 to binimetinib and 133 to dacarbazine. Median follow-up was 1·7 months (IQR 1·4–4·1). Median progression-free survival was 2·8 months (95% CI 2·8–3·6) in the binimetinib group and 1·5 months (1·5–1·7) in the dacarbazine group (hazard ratio 0·62 [95% CI 0·47–0·80]; one-sided p vs none of 114 in the dacarbazine group), hypertension (20 [7%] vs two [2%]), anaemia (five [2%] vs six [5%]), and neutropenia (two [1%] vs ten [9%]). Serious adverse events (all grades) occurred in 91 (34%) patients in the binimetinib group and 25 (22%) patients in the dacarbazine group. Interpretation Binimetinib improved progression-free survival compared with dacarbazine and was tolerable. Binimetinib might represent a new treatment option for patients with NRAS -mutant melanoma after failure of immunotherapy. Funding Array BioPharma and Novartis Pharmaceuticals Corporation.read more
Citations
More filters
Journal ArticleDOI
Comprehensive Characterization of Cancer Driver Genes and Mutations.
Matthew H. Bailey,Collin Tokheim,Eduard Porta-Pardo,Sohini Sengupta,Denis Bertrand,Amila Weerasinghe,Antonio Colaprico,Michael C. Wendl,Jaegil Kim,Brendan Reardon,Patrick Kwok Shing Ng,Kang Jin Jeong,Song Cao,Zixing Wang,Jianjiong Gao,Qingsong Gao,Fang Wang,Eric Minwei Liu,Loris Mularoni,Carlota Rubio-Perez,Niranjan Nagarajan,Isidro Cortes-Ciriano,Daniel Cui Zhou,Wen-Wei Liang,Julian M. Hess,Venkata Yellapantula,David Tamborero,Abel Gonzalez-Perez,Chayaporn Suphavilai,Jia Yu Ko,Ekta Khurana,Peter J. Park,Eliezer M. Van Allen,Eliezer M. Van Allen,Han Liang,Michael S. Lawrence,Adam Godzik,Nuria Lopez-Bigas,Josh Stuart,David A. Wheeler,Gad Getz,Ken Chen,Alexander J. Lazar,Gordon B. Mills,Rachel Karchin,Li Ding +45 more
TL;DR: This study reports a PanCancer and PanSoftware analysis spanning 9,423 tumor exomes (comprising all 33 of The Cancer Genome Atlas projects) and using 26 computational tools to catalog driver genes and mutations, identifying 299 driver genes with implications regarding their anatomical sites and cancer/cell types.
Journal ArticleDOI
Cutaneous melanoma, version 2.2019
Daniel G. Coit,John A. Thompson,Mark R. Albertini,Christopher A. Barker,William E. Carson,Carlo M. Contreras,Gregory A. Daniels,Dominick J. DiMaio,Ryan C. Fields,Martin D. Fleming,Morganna Freeman,Anjela Galan,Brian R. Gastman,Valerie Guild,Douglas B. Johnson,Richard W. Joseph,Julie R. Lange,Sameer K. Nath,Anthony J. Olszanski,Patrick A. Ott,Aparna Priyanath Gupta,Merrick I. Ross,April K.S. Salama,Joseph J. Skitzki,Jeffrey A. Sosman,Susan M. Swetter,Kenneth K. Tanabe,Evan Wuthrick,Nicole R. McMillian,Anita M. Engh +29 more
TL;DR: The data and rationale supporting extensive changes to the recommendations for systemic therapy as adjuvant treatment of resected disease and as treatment of unresectable or distant metastatic disease are summarized.
Journal ArticleDOI
Classifying BRAF alterations in cancer: new rational therapeutic strategies for actionable mutations.
TL;DR: Pre-clinical and clinical findings that may lead to improved treatments for all classes of BRAF mutant cancers are discussed, including those that predict response to targeted therapies and have important implications for future drug development.
Journal ArticleDOI
Survival of patients with advanced metastatic melanoma: the impact of novel therapies-update 2017.
Selma Ugurel,Joachim Röhmel,Paolo A. Ascierto,Keith T. Flaherty,Jean-Jacques Grob,Axel Hauschild,James Larkin,Georgina V. Long,Paul Lorigan,Grant A. McArthur,Antoni Ribas,Caroline Robert,Dirk Schadendorf,Claus Garbe +13 more
TL;DR: An exploratory analysis of survival data from selected clinical trials representative for the new treatment strategies in advanced metastatic melanoma revealed a high concordance between kinase inhibitors and checkpoint blockers, particularly in the first-line setting.
Journal ArticleDOI
The current state of molecular testing in the treatment of patients with solid tumors, 2019
Wafik S. El-Deiry,Richard M. Goldberg,Heinz-Josef Lenz,Anthony F. Shields,Geoffrey T. Gibney,Antoinette R. Tan,Jubilee Brown,Burton L. Eisenberg,Elisabeth I. Heath,Surasak Phuphanich,Edward J. Kim,Andrew Brenner,John L. Marshall +12 more
TL;DR: The authors provide the current state of the art for molecular profiling/precision medicine, practice standards, and a view into the future ahead.
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 Vemurafenib in Melanoma with BRAF V600E Mutation
Paul B. Chapman,Axel Hauschild,Caroline Robert,John B. A. G. Haanen,Paolo A. Ascierto,James Larkin,Reinhard Dummer,Claus Garbe,Alessandro Testori,Michele Maio,David W. Hogg,Paul Lorigan,Céleste Lebbé,Thomas Jouary,Dirk Schadendorf,Antoni Ribas,Jeffrey A. Sosman,John M. Kirkwood,Brigitte Dréno,K. B. Nolop,Jiang Li,B. Nelson,Jeannie Hou,Richard J. Lee,Keith T. Flaherty,Grant A. McArthur +25 more
TL;DR: Vemurafenib produced improved rates of overall and progression-free survival in patients with previously untreated melanoma with the BRAF V600E mutation in a phase 3 randomized clinical trial.
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
Ipilimumab plus Dacarbazine for Previously Untreated Metastatic Melanoma
Caroline Robert,Luc Thomas,Igor Bondarenko,Steven J. O'Day,Jeffrey S. Weber,Claus Garbe,Céleste Lebbé,Jean Francois Baurain,Alessandro Testori,Jean-Jacques Grob,Neville Davidson,Jon M. Richards,Michele Maio,Axel Hauschild,Wilson H. Miller,Pere Gascón,Michal Lotem,Kaan Harmankaya,Ramy Ibrahim,Stephen Francis,Tai-Tsang Chen,R. Humphrey,Axel Hoos,Jedd D. Wolchok +23 more
TL;DR: Ipilimumab (at a dose of 10 mg per kilogram) in combination with dacarbazine, as compared with dACarbazine plus placebo, improved overall survival in patients with previously untreated metastatic melanoma.
Journal Article
[New response evaluation criteria in solid tumours-revised RECIST guideline (version 1.1)].
Hirokazu Watanabe,Morihito Okada,Yasushi Kaji,Miyako Satouchi,Yozo Sato,Yuichiro Yamabe,Hiroaki Onaya,Masahiro Endo,Miyuki Sone,Yasuaki Arai +9 more
TL;DR: This paper is an overview of the new response evaluation criteria in solid tumours: revised RECIST guideline (version 1. 1), with a focus on updated contents.
Related Papers (5)
Improved Survival with Vemurafenib in Melanoma with BRAF V600E Mutation
Paul B. Chapman,Axel Hauschild,Caroline Robert,John B. A. G. Haanen,Paolo A. Ascierto,James Larkin,Reinhard Dummer,Claus Garbe,Alessandro Testori,Michele Maio,David W. Hogg,Paul Lorigan,Céleste Lebbé,Thomas Jouary,Dirk Schadendorf,Antoni Ribas,Jeffrey A. Sosman,John M. Kirkwood,Brigitte Dréno,K. B. Nolop,Jiang Li,B. Nelson,Jeannie Hou,Richard J. Lee,Keith T. Flaherty,Grant A. McArthur +25 more
Genomic Classification of Cutaneous Melanoma
Rehan Akbani,Kadir C. Akdemir,B. Arman Aksoy,Monique Albert,Adrian Ally,Samirkumar B. Amin,Harindra Arachchi,Arshi Arora,J. Todd Auman,Brenda Ayala,Julien Baboud,Miruna Balasundaram,Saianand Balu,Nandita Barnabas,John M. S. Bartlett,Pam Bartlett,Boris C. Bastian,Stephen B. Baylin,Madhusmita Behera,Dmitry Belyaev,Christopher C. Benz,Brady Bernard,Rameen Beroukhim,Natalie Bir,Aaron D. Black,Tom Bodenheimer,Lori Boice,Genevieve M. Boland,Riccardo Bono,Moiz S. Bootwalla,Marcus Bosenberg,Jay Bowen,Reanne Bowlby,Christopher A. Bristow,Laura Brockway-Lunardi,Denise Brooks,Jakub Brzezinski,Wiam Bshara,Elizabeth Buda,William R. Burns,Yaron S.N. Butterfield,Michael Button,Tiffany L. Calderone,Giancarlo Antonini Cappellini,Candace D. Carter,Scott L. Carter,Lynn Cherney,Andrew D. Cherniack,Aaron Chevalier,Lynda Chin,Juok Cho,Raymond J. Cho,Yoon La Choi,Andy Chu,Sudha Chudamani,Kristian Cibulskis,Giovanni Ciriello,Amanda Clarke,Stephen Coons,Leslie Cope,Daniel Crain,Erin Curley,Ludmila Danilova,Stefania D'Atri,Tanja Davidsen,Michael A. Davies,Keith A. Delman,John A. Demchok,Qixia A. Deng,Yonathan Lissanu Deribe,Noreen Dhalla,Rajiv Dhir,Daniel DiCara,Michael Dinikin,Michael Dubina,J. Stephen Ebrom,Sophie Egea,Greg Eley,Jay Engel,Jennifer Eschbacher,Konstantin V. Fedosenko,Ina Felau,Timothy R. Fennell,Martin L. Ferguson,Sheila Fisher,Keith T. Flaherty,Scott Frazer,Jessica Frick,Victoria Fulidou,Stacey Gabriel,Jianjiong Gao,Johanna Gardner,Levi A. Garraway,Julie M. Gastier-Foster,Carmelo Gaudioso,Nils Gehlenborg,Giannicola Genovese,Mark Gerken,Jeffrey E. Gershenwald,Gad Getz,Carmen Gomez-Fernandez,Thomas Gribbin,Jonna Grimsby,Benjamin Gross,Ranabir Guin,Tony Gutschner,Angela Hadjipanayis,Ruth Halaban,Benjamin Hanf,David Haussler,Lauren E. Haydu,D. Neil Hayes,Nicholas K. Hayward,David I. Heiman,Lynn M. Herbert,James G. Herman,Peter Hersey,Katherine A. Hoadley,Eran Hodis,Robert A. Holt,Dave S.B. Hoon,Susan Hoppough,Alan P. Hoyle,Franklin W. Huang,Mei Huang,Sharon K. Huang,Carolyn M. Hutter,Matthew Ibbs,Lisa Iype,Anders Jacobsen,Valerie Jakrot,Alyssa Janning,William R. Jeck,Stuart R. Jefferys,Mark A. Jensen,Corbin D. Jones,Steven J.M. Jones,Zhenlin Ju,Hojabr Kakavand,Hyojin Kang,Richard F. Kefford,Fadlo R. Khuri,Jaegil Kim,John M. Kirkwood,Joachim Klode,Anil Korkut,Konstanty Korski,Michael Krauthammer,Raju Kucherlapati,Lawrence N. Kwong,Witold Kycler,Marc Ladanyi,Phillip H. Lai,Peter W. Laird,Eric S. Lander,Michael S. Lawrence,Alexander J. Lazar,Radoslaw Łaźniak,Darlene Lee,Jeffrey E. Lee,Junehawk Lee,Kenneth K. Lee,Semin Lee,William Lee,Ewa Leporowska,Kristen M. Leraas,Haiyan I. Li,Tara M. Lichtenberg,Lee Lichtenstein,Pei Lin,Shiyun Ling,Jia Liu,Ouida Liu,Wen-Bin Liu,Georgina V. Long,Yiling Lu,Singer Ma,Yussanne Ma,Andrzej Mackiewicz,Harshad S. Mahadeshwar,Jared Malke,David Mallery,Georgy Manikhas,Graham J. Mann,Marco A. Marra,Brenna Matejka,Michael Mayo,Sousan Mehrabi,Shaowu Meng,Matthew Meyerson,Piotr A. Mieczkowski,John P. Miller,Martin L. Miller,Gordon B. Mills,Fedor Moiseenko,Richard A. Moore,Scott Morris,Carl Morrison,Donald L. Morton,Stergios J. Moschos,Lisle E. Mose,Florian L. Muller,Andrew J. Mungall,D. Murawa,Pawel Murawa,Bradley A. Murray,Luigi Nezi,Sam Ng,Dana Nicholson,Michael S. Noble,Adeboye Osunkoya,Taofeek K. Owonikoko,Bradley A. Ozenberger,Elena Pagani,Oxana Paklina,Angeliki Pantazi,Michael Parfenov,Jeremy Parfitt,Peter J. Park,Woong-Yang Park,Joel S. Parker,Francesca Passarelli,Robert Penny,Charles M. Perou,Todd Pihl,Olga Potapova,Victor G. Prieto,Alexei Protopopov,Michael J. Quinn,Amie Radenbaugh,Kunal Rai,Suresh Ramalingam,Ayush T. Raman,Nilsa C. Ramirez,Ricardo Ramirez,Uma Rao,W. Kimryn Rathmell,Xiaojia Ren,Sheila Reynolds,Jeffrey Roach,A. Gordon Robertson,Merrick I. Ross,Jason Roszik,Giandomenico Russo,Gordon Saksena,Charles Saller,Yardena Samuels,Chris Sander,Cindy Sander,George E. Sandusky,Netty Santoso,Melissa Saul,Robyn P. M. Saw,Dirk Schadendorf,Jacqueline E. Schein,Nikolaus Schultz,Steven E. Schumacher,Charles Schwallier,Richard A. Scolyer,Jonathan G. Seidman,Pedamallu Chandra Sekhar,Harmanjatinder S. Sekhon,Yasin Senbabaoglu,Sahil Seth,Kerwin F. Shannon,Samantha Sharpe,Norman E. Sharpless,Kenna R. Mills Shaw,Candace Shelton,Troy Shelton,Ronglai Shen,Margi Sheth,Yan Shi,Carolyn J. Shiau,Ilya Shmulevich,Gabriel Sica,Janae V. Simons,Rileen Sinha,Payal Sipahimalani,Heidi J. Sofia,Matthew G. Soloway,Xingzhi Song,Carrie Sougnez,Andrew J. Spillane,Arkadiusz Spychała,Jonathan R. Stretch,Joshua M. Stuart,Wiktoria Maria Suchorska,Antje Sucker,S. Onur Sumer,Yichao Sun,Maria Synott,Barbara Tabak,Teresa R. Tabler,Angela Tam,Donghui Tan,Jiabin Tang,Roy Tarnuzzer,Katherine Tarvin,Honorata Tatka,Barry S. Taylor,M. Teresiak,Nina Thiessen,John F. Thompson,Leigh B. Thorne,Vesteinn Thorsson,Jeffrey M. Trent,Timothy J. Triche,Kenneth Y. Tsai,Peiling Tsou,David Van Den Berg,Eliezer M. Van Allen,Umadevi Veluvolu,Roeland Verhaak,Douglas Voet,Olga Voronina,Vonn Walter,Jessica Walton,Yunhu Wan,Yuling Wang,Zhining Wang,Scot Waring,Ian R. Watson,Nils Weinhold,John N. Weinstein,Daniel J. Weisenberger,Peter White,Matthew D. Wilkerson,James S. Wilmott,Lisa Wise,Maciej Wiznerowicz,Scott E. Woodman,Chang Jiun Wu,Chia Chin Wu,Junyuan Wu,Ye Wu,Ruibin Xi,Andrew Wei Xu,Da Yang,Liming Yang,Lixing Yang,Travis I. Zack,Jean C. Zenklusen,Hailei Zhang,Jianhua Zhang,Wei Zhang,Xiaobei Zhao,Jingchun Zhu,Kelsey Zhu,Lisa Zimmer,Erik Zmuda,Lihua Zou +351 more
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
Dabrafenib in BRAF-mutated metastatic melanoma: a multicentre, open-label, phase 3 randomised controlled trial
Axel Hauschild,Jean-Jacques Grob,Lev V. Demidov,Thomas Jouary,Ralf Gutzmer,Michael Millward,Piotr Rutkowski,Christian U. Blank,Wilson H. Miller,Eckhart Kaempgen,Salvador Martín-Algarra,Boguslawa Karaszewska,Cornelia Mauch,Vanna Chiarion-Sileni,Anne-Marie Martin,Suzanne Swann,Patricia Haney,Beloo Mirakhur,Mary E. Guckert,Vicki L. Goodman,Paul B. Chapman +20 more
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