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
Reads0
Chats0
TLDR
Ipilimumab, with or without a gp100 peptide vaccine, as compared with gp100 alone, improved overall survival in patients with previously treated metastatic melanoma.Abstract:
Background An improvement in overall survival among patients with metastatic melanoma has been an elusive goal. In this phase 3 study, ipilimumab — which blocks cytotoxic T-lymphocyte–associated antigen 4 to potentiate an antitumor T-cell response — administered with or without a glycoprotein 100 (gp100) peptide vaccine was compared with gp100 alone in patients with previously treated metastatic melanoma. Methods A total of 676 HLA-A*0201–positive patients with unresectable stage III or IV melanoma, whose disease had progressed while they were receiving therapy for metastatic disease, were randomly assigned, in a 3:1:1 ratio, to receive ipilimumab plus gp100 (403 patients), ipilimumab alone (137), or gp100 alone (136). Ipilimumab, at a dose of 3 mg per kilogram of body weight, was administered with or without gp100 every 3 weeks for up to four treatments (induction). Eligible patients could receive reinduction therapy. The primary end point was overall survival. Results The median overall survival was 10.0 months among patients receiving ipilimumab plus gp100, as compared with 6.4 months among patients receiving gp100 alone (hazard ratio for death, 0.68; P<0.001). The median overall survival with ipilimumab alone was 10.1 months (hazard ratio for death in the comparison with gp100 alone, 0.66; P = 0.003). No difference in overall survival was detected between the ipilimumab groups (hazard ratio with ipilimumab plus gp100, 1.04; P = 0.76). Grade 3 or 4 immune-related adverse events occurred in 10 to 15% of patients treated with ipilimumab and in 3% treated with gp100 alone. There were 14 deaths related to the study drugs (2.1%), and 7 were associated with immune-related adverse events. Conclusions Ipilimumab, with or without a gp100 peptide vaccine, as compared with gp100 alone, improved overall survival in patients with previously treated metastatic melanoma. Adverse events can be severe, long-lasting, or both, but most are reversible with appropriate treatment. (Funded by Medarex and Bristol-Myers Squibb; ClinicalTrials.gov number, NCT00094653.)read more
Citations
More filters
Journal ArticleDOI
PD-1 Inhibitor–Related Pneumonitis in Advanced Cancer Patients: Radiographic Patterns and Clinical Course
Mizuki Nishino,Nikhil H. Ramaiya,Mark M. Awad,Lynette M. Sholl,Jennifer A. Maattala,Myriam Taibi,Hiroto Hatabu,Patrick A. Ott,Philippe Armand,F. Stephen Hodi +9 more
TL;DR: PD-1 inhibitor–related pneum onitis showed a spectrum of radiographic patterns, reflecting pneumonitis grades, and was the most common pattern across tumor types and therapeutic regimens.
Journal ArticleDOI
Intrinsic and extrinsic control of peripheral T‐cell tolerance by costimulatory molecules of the CD28/ B7 family
Hélène Bour-Jordan,Jonathan H. Esensten,Marc Martinez-Llordella,Cristina Penaranda,Melanie Stumpf,Jeffrey A. Bluestone +5 more
TL;DR: Positive and negative costimulation by members of the CD28 family is critical for the development of productive immune responses against foreign pathogens and their proper termination to prevent inflammation‐induced tissue damage.
Journal ArticleDOI
Robust tumor immunity to melanoma mediated by interleukin-9-producing T cells
Rahul Purwar,Christoph Schlapbach,Sheng Xiao,Hong Soon Kang,Wassim Elyaman,Xiaodong Jiang,Anton M. Jetten,Samia J. Khoury,Robert C. Fuhlbrigge,Vijay K. Kuchroo,Rachael A. Clark,Thomas S. Kupper +11 more
TL;DR: A role for IL-9 in tumor immunity and insight into potential therapeutic strategies is suggested and higher numbers of TH9 cells in normal human skin and blood compared to metastatic lesions of subjects with progressive stage IV melanoma are found.
Journal ArticleDOI
Overall Survival in Patients With Advanced Melanoma Who Received Nivolumab Versus Investigator's Choice Chemotherapy in CheckMate 037: A Randomized, Controlled, Open-Label Phase III Trial.
James Larkin,David R. Minor,Sandra P. D'Angelo,Bart Neyns,Michael Smylie,Wilson H. Miller,Ralf Gutzmer,Gerald P. Linette,Bartosz Chmielowski,Christopher D. Lao,Paul Lorigan,Kenneth F. Grossmann,Jessica C. Hassel,Mario Sznol,Adil Daud,Jeffrey A. Sosman,Nikhil I. Khushalani,Dirk Schadendorf,Christoph Hoeller,Dana Walker,George Kong,Christine Horak,Jeffrey S. Weber,Jeffrey S. Weber +23 more
TL;DR: The coprimary overall survival (OS) end point of CheckMate 037 is reported, which has previously shown that nivolumab resulted in more patients achieving an objective response compared with chemotherapy regimens in ipilimumab-refractory patients with advanced melanoma.
Journal ArticleDOI
Induction of T-cell Immunity Overcomes Complete Resistance to PD-1 and CTLA-4 Blockade and Improves Survival in Pancreatic Carcinoma.
Rafael Winograd,Katelyn T. Byrne,Rebecca A. Evans,Pamela M. Odorizzi,Anders R.L. Meyer,David L. Bajor,Cynthia Clendenin,Ben Z. Stanger,Emma E. Furth,E. John Wherry,Robert H. Vonderheide +10 more
TL;DR: It is suggested that in pancreatic carcinoma, a nonimmunogenic tumor, baseline refractoriness to checkpoint inhibitors can be rescued by the priming of a T-cell response with αCD40/chemotherapy.
References
More filters
Journal ArticleDOI
Toxicity and response criteria of the Eastern Cooperative Oncology Group
Martin M. Oken,Richard H. Creech,Douglass C. Tormey,John Horton,Thomas E. Davis,Eleanor T. McFadden,Paul P. Carbone +6 more
TL;DR: The Eastern Cooperative Oncology Group criteria for toxicity and response are presented to facilitate future reference and to encourage further standardization among those conducting clinical trials.
Journal ArticleDOI
Cancer immunotherapy: moving beyond current vaccines.
TL;DR: Results in cancer vaccine trials are considered and alternate strategies that mediate cancer regression in preclinical and clinical models are highlighted.
Journal ArticleDOI
Guidelines for the Evaluation of Immune Therapy Activity in Solid Tumors: Immune-Related Response Criteria
Jedd D. Wolchok,Axel Hoos,Steven J. O'Day,Jeffrey S. Weber,Omid Hamid,Céleste Lebbé,Michele Maio,Michael Binder,Oliver Bohnsack,Geoffrey M. Nichol,R. Humphrey,F. Stephen Hodi +11 more
TL;DR: Systematic criteria, designated immune-related response criteria, were defined in an attempt to capture additional response patterns observed with immune therapy in advanced melanoma beyond those described by Response Evaluation Criteria in Solid Tumors or WHO criteria.
Journal ArticleDOI
Melanoma biology and new targeted therapy
TL;DR: The incidence of melanoma is rising steadily in western populations — the number of cases worldwide has doubled in the past 20 years — and these advances are being exploited to provide targeted drugs and new therapeutic approaches.
Journal ArticleDOI
Ipilimumab monotherapy in patients with pretreated advanced melanoma: a randomised, double-blind, multicentre, phase 2, dose-ranging study
Jedd D. Wolchok,Bart Neyns,Gerald P. Linette,Sylvie Negrier,Jose Lutzky,Luc Thomas,William Waterfield,Dirk Schadendorf,Michael Smylie,Troy H. Guthrie,Jean-Jacques Grob,Jason Chesney,Kevin M. Chin,Kun Chen,Axel Hoos,Steven J. O'Day,Céleste Lebbé +16 more
TL;DR: Ipilimumab elicited a dose-dependent effect on efficacy and safety measures in pretreated patients with advanced melanoma, lending support to further studies at a dose of 10 mg/kg.
Related Papers (5)
Safety, activity, and immune correlates of anti-PD-1 antibody in cancer.
Suzanne L. Topalian,F. Stephen Hodi,Julie R. Brahmer,Scott N. Gettinger,David Smith,David F. McDermott,John D. Powderly,Richard D. Carvajal,Jeffrey A. Sosman,Michael B. Atkins,Philip D. Leming,David R. Spigel,Scott J. Antonia,Leora Horn,Charles G. Drake,Drew M. Pardoll,Lieping Chen,William H. Sharfman,Robert A. Anders,Janis M. Taube,Tracee L. McMiller,Haiying Xu,Alan J. Korman,Maria Jure-Kunkel,Shruti Agrawal,Dan McDonald,Georgia Kollia,Ashok Kumar Gupta,Jon M. Wigginton,Mario Sznol +29 more
Combined Nivolumab and Ipilimumab or Monotherapy in Untreated Melanoma.
James Larkin,Vanna Chiarion-Sileni,Rene Gonzalez,Jean-Jacques Grob,C. Lance Cowey,Christopher D. Lao,Dirk Schadendorf,Reinhard Dummer,Michael Smylie,Piotr Rutkowski,Pier Francesco Ferrucci,A. Hill,John Wagstaff,Matteo S. Carlino,John B A G Haanen,Michele Maio,Ivan Marquez-Rodas,Grant A. McArthur,Paolo A. Ascierto,Georgina V. Long,Margaret K. Callahan,Michael A. Postow,Michael A. Postow,Kenneth F. Grossmann,Mario Sznol,Brigitte Dréno,Lars Bastholt,Arvin Yang,Linda Rollin,Christine Horak,F. Stephen Hodi,Jedd D. Wolchok,Jedd D. Wolchok +32 more
Safety and Activity of Anti–PD-L1 Antibody in Patients with Advanced Cancer
Julie R. Brahmer,Scott S. Tykodi,Scott S. Tykodi,Laura Q.M. Chow,Wen-Jen Hwu,Suzanne L. Topalian,Patrick Hwu,Charles G. Drake,Luis H. Camacho,John S. Kauh,Kunle Odunsi,Henry C. Pitot,Omid Hamid,Shailender Bhatia,Renato G. Martins,Keith D. Eaton,Shuming Chen,Theresa M. Salay,Suresh Alaparthy,Joseph F. Grosso,Alan J. Korman,Susan M. Parker,Shruti Agrawal,Stacie M. Goldberg,Drew M. Pardoll,Ashok Kumar Gupta,Jon M. Wigginton +26 more
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
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