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
Improved Endpoints for Cancer Immunotherapy Trials
Axel Hoos,Alexander M.M. Eggermont,Sylvia Janetzki,F. Stephen Hodi,Ramy Ibrahim,Aparna Anderson,R. Humphrey,Brent A. Blumenstein,Lloyd Old,Jedd D. Wolchok +9 more
TL;DR: A body of clinical and laboratory data was generated that supports three novel endpoint recommendations that may improve tools for cancer immunotherapy trials and may offer a more realistic and useful model for clinical investigation.
Journal ArticleDOI
Durable Cancer Regression Off-Treatment and Effective Reinduction Therapy with an Anti-PD-1 Antibody
Evan J. Lipson,William H. Sharfman,Charles G. Drake,Ira Wollner,Janis M. Taube,Robert A. Anders,Haiying Xu,Sheng Yao,Alice Pons,Lieping Chen,Drew M. Pardoll,Julie R. Brahmer,Suzanne L. Topalian +12 more
TL;DR: These data represent the most prolonged observation to date of patients with solid tumors responding to anti- PD-1 immunotherapy and the first report of successful reinduction therapy following delayed tumor progression, and underscore the potential for immune checkpoint blockade with anti-PD-1 to reset the equilibrium between tumor and the host immune system.
Journal ArticleDOI
Tim‐3 and its role in regulating anti‐tumor immunity
TL;DR: Tim‐3 has gained prominence as a potential candidate for cancer immunotherapy, where it has been shown that in vivo blockade of Tim‐3 with other check‐point inhibitors enhances anti‐tumor immunity and suppresses tumor growth in several preclinical tumor models.
Journal ArticleDOI
Targeted delivery of a PD-1-blocking scFv by CAR-T cells enhances anti-tumor efficacy in vivo
Sarwish Rafiq,Oladapo Yeku,Hollie J. Jackson,Terence J. Purdon,Dayenne G. van Leeuwen,Dylan J. Drakes,Mei Song,Matthew M. Miele,Zhuoning Li,Pei Wang,Su Yan,Jingyi Xiang,Xiaojing Ma,Venkatraman E. Seshan,Ronald C. Hendrickson,Cheng Liu,Renier J. Brentjens,Renier J. Brentjens +17 more
TL;DR: This work modified CAR-T cells to secrete PD-1-blocking single-chain variable fragments (scFv), which acted in both a paracrine and autocrine manner to improve the anti-tumor activity of CAR- T cells and bystander tumor-specific T cells in clinically relevant syngeneic and xenogeneic mouse models of PD-L1+ hematologic and solid tumors.
Journal ArticleDOI
Toxicities of Immunotherapy for the Practitioner
TL;DR: The toxicities that are unique to immunotherapies are summarized, emphasizing the need to familiarize the oncology practitioner with the spectrum of adverse events seen with newly approved and emerging modalities.
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