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
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
TL;DR: Anti-PD-1 antibody produced objective responses in approximately one in four to one in five patients with non-small-cell lung cancer, melanoma, or renal-cell cancer; the adverse-event profile does not appear to preclude its use.
Journal ArticleDOI
The blockade of immune checkpoints in cancer immunotherapy
TL;DR: Preliminary clinical findings with blockers of additional immune-checkpoint proteins, such as programmed cell death protein 1 (PD1), indicate broad and diverse opportunities to enhance antitumour immunity with the potential to produce durable clinical responses.
Journal ArticleDOI
Nivolumab versus Docetaxel in Advanced Nonsquamous Non–Small-Cell Lung Cancer
Hossein Borghaei,Luis Paz-Ares,Leora Horn,D. R. Spigel,M. Steins,Neal Ready,L.Q. Chow,Everett E. Vokes,Enriqueta Felip,Esther Holgado,F. Barlesi,M. Kohlhufl,Oscar Arrieta,Marco Angelo Burgio,J. Fayette,H. Lena,Elena Poddubskaya,David E. Gerber,Scott N. Gettinger,Charles M. Rudin,Naiyer A. Rizvi,L. Crina,G. R. Blumenschein,Scott J. Antonia,C. Dorange,C. T. Harbison,F. Graf Finckenstein,Julie R. Brahmer +27 more
TL;DR: Nivolumab was associated with even greater efficacy than docetaxel across all end points in subgroups defined according to prespecified levels of tumor-membrane expression (≥1, ≥5%, and ≥10%) of the PD-1 ligand.
Journal ArticleDOI
Pembrolizumab versus Chemotherapy for PD-L1–Positive Non–Small-Cell Lung Cancer
Martin Reck,Delvys Rodriguez-Abreu,Andrew G. Robinson,Rina Hui,Tibor Csőszi,Andrea Fülöp,Maya Gottfried,Nir Peled,Ali Tafreshi,Sinead Cuffe,Mary O'Brien,Suman Rao,Katsuyuki Hotta,Melanie A. Leiby,Gregory M. Lubiniecki,Yue Shentu,Reshma A. Rangwala,Julie R. Brahmer +17 more
TL;DR: Pembrolizumab is a humanized monoclonal antibody against programmed death 1 (PD-1) that has antitumor activity in advanced non-small-cell lung cancer (NSCLC), with increased activity in tumors that express PD-L1 as mentioned in this paper.
Journal ArticleDOI
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
TL;DR: Antibody-mediated blockade of PD-L1 induced durable tumor regression and prolonged stabilization of disease in patients with advanced cancers, including non-small-cell lung cancer, melanoma, and renal-cell cancer.
References
More filters
Journal ArticleDOI
Single-agent interleukin-2 in the treatment of metastatic melanoma.
TL;DR: This systematic review suggests that patients with a good performance status, a normal lactate dehydrogenase level, less than three organs involved or cutaneous and/or subcutaneous metastases, have the highest probability of responding and achieving a durable complete response to single-agent interleukin-2.
Journal ArticleDOI
Current management of metastatic melanoma.
TL;DR: New strategies are needed to improve treatment response rates and duration of overall survival in patients with metastatic melanoma.
Journal ArticleDOI
EORTC 18961: Post-operative adjuvant ganglioside GM2-KLH21 vaccination treatment vs observation in stage II (T3-T4N0M0) melanoma: 2nd interim analysis led to an early disclosure of the results
A. M. M. Eggermont,Stefan Suciu,W. Ruka,J. Marsden,Alessandro Testori,Pippa Corrie,Steinar Aamdal,P.A. Ascierto,Poulam M. Patel,Alan Spatz +9 more
TL;DR: The largest adjuvant phase III trial to date in stage II melanoma the efficacy and toxicity of Ganglioside GM2-KLH21 Vaccination (VAC) Treatment vs Observat...
Journal ArticleDOI
Results of a multicenter, randomized, double-blind phase 2/3 study of lenalidomide in the treatment of pretreated relapsed or refractory metastatic malignant melanoma.
Tim Eisen,Uwe Trefzer,Anne Hamilton,Peter Hersey,Michael Millward,Robert Knight,Jarl U. Jungnelius,John A. Glaspy +7 more
TL;DR: The results of an international, multicenter, randomized, double‐blind, controlled study assessing the efficacy and safety of lenalidomide treatment in patients with refractory stage IV metastatic malignant melanoma are reported.
Journal ArticleDOI
Novel immunotherapies as potential therapeutic partners for traditional or targeted agents: cytotoxic T-lymphocyte antigen-4 blockade in advanced melanoma.
TL;DR: Novel combinations of molecular targeted agents that inhibit the proliferation and survival of metastatic melanoma cells offer potential partners for anti-CTLA-4 antibodies in combined modality regimens.
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