Nivolumab plus Ipilimumab in Advanced Melanoma
Jedd D. Wolchok,Harriet Kluger,Margaret K. Callahan,Michael A. Postow,Naiyer A. Rizvi,Alexander M. Lesokhin,Neil H. Segal,Charlotte E. Ariyan,Ruth-Ann Gordon,Kathleen Reed,Matthew M. Burke,Anne Caldwell,Stephanie Anne Kronenberg,Blessing Agunwamba,Xiaoling Zhang,Israel Lowy,Hector David Inzunza,William Feely,Christine Horak,Quan Hong,Alan J. Korman,Jon M. Wigginton,Ashok Kumar Gupta,Mario Sznol +23 more
TLDR
Conurrent therapy with nivolumab and ipilimumab had a manageable safety profile and provided clinical activity that appears to be distinct from that in published data on monotherapy, with rapid and deep tumor regression in a substantial proportion of patients.Abstract:
A total of 53 patients received concurrent therapy with nivolumab and ipilimumab, and 33 received sequenced treatment. The objective-response rate (according to modified World Health Organization criteria) for all patients in the concurrent-regimen group was 40%. Evidence of clinical activity (conventional, unconfirmed, or immune-related response or stable disease for ≥24 weeks) was observed in 65% of patients. At the maximum doses that were associated with an acceptable level of adverse events (nivolumab at a dose of 1 mg per kilogram of body weight and ipilimumab at a dose of 3 mg per kilogram), 53% of patients had an objective response, all with tumor reduction of 80% or more. Grade 3 or 4 adverse events related to therapy occurred in 53% of patients in the concurrent-regimen group but were qualitatively similar to previous experience with monotherapy and were generally reversible. Among patients in the sequenced-regimen group, 18% had grade 3 or 4 adverse events related to therapy and the objective-response rate was 20%. CONCLUSIONS Concurrent therapy with nivolumab and ipilimumab had a manageable safety profile and provided clinical activity that appears to be distinct from that in published data on monotherapy, with rapid and deep tumor regression in a substantial proportion of patients. (Funded by Bristol-Myers Squibb and Ono Pharmaceutical; ClinicalTrials.gov number, NCT01024231.)read more
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Journal ArticleDOI
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
TL;DR: Among previously untreated patients with metastatic melanoma, nivolumab alone or combined with ipilimumab resulted in significantly longer progression-free survival than ipILimumab alone, and in patients with PD-L1-negative tumors, the combination of PD-1 and CTLA-4 blockade was more effective than either agent alone.
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Mutational landscape determines sensitivity to PD-1 blockade in non–small cell lung cancer
Naiyer A. Rizvi,Naiyer A. Rizvi,Matthew D. Hellmann,Matthew D. Hellmann,Alexandra Snyder,Alexandra Snyder,Pia Kvistborg,Vladimir Makarov,Jonathan J. Havel,William Lee,Jianda Yuan,Phillip Wong,Teresa S. Ho,Martin L. Miller,Natasha Rekhtman,Andre L. Moreira,Fawzia Ibrahim,Cameron Bruggeman,Billel Gasmi,Roberta Zappasodi,Yuka Maeda,Chris Sander,Edward B. Garon,Taha Merghoub,Jedd D. Wolchok,Jedd D. Wolchok,Ton N. Schumacher,Timothy A. Chan,Timothy A. Chan +28 more
TL;DR: Treatment efficacy was associated with a higher number of mutations in the tumors, and a tumor-specific T cell response paralleled tumor regression in one patient, suggesting that the genomic landscape of lung cancers shapes response to anti–PD-1 therapy.
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Microenvironmental regulation of tumor progression and metastasis.
TL;DR: The paradoxical roles of the tumor microenvironment during specific stages of cancer progression and metastasis are discussed, as well as recent therapeutic attempts to re-educate stromal cells within the TME to have anti-tumorigenic effects.
Journal ArticleDOI
PD-1 blockade induces responses by inhibiting adaptive immune resistance
Paul C. Tumeh,Christina L. Harview,Jennifer H. Yearley,I. Peter Shintaku,Emma Taylor,Lidia Robert,Bartosz Chmielowski,Marko Spasic,Gina Henry,Voicu Ciobanu,Alisha N. West,Manuel Carmona,Christine Kivork,Elizabeth Seja,Grace Cherry,Antonio Gutierrez,Tristan Grogan,Christine Mateus,Gorana Tomasic,John A. Glaspy,Ryan O. Emerson,Harlan Robins,Robert H. Pierce,David Elashoff,Caroline Robert,Antoni Ribas +25 more
TL;DR: It is shown that pre-existing CD8+ T cells distinctly located at the invasive tumour margin are associated with expression of the PD-1/PD-L1 immune inhibitory axis and may predict response to therapy.
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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
TL;DR: The anti-PD-1 antibody pembrolizumab prolonged progression-free survival and overall survival and had less high-grade toxicity than did ipilimumab in patients with advanced melanoma.
References
More filters
Journal ArticleDOI
Gastrosplenic Fistula From Hodgkin's Lymphoma
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
Single-institution experience with ipilimumab in advanced melanoma patients in the compassionate use setting lymphocyte count after 2 doses correlates with survival
Geoffrey Y. Ku,Jianda Yuan,David B. Page,Sebastian Edoardo Artur Schroeder,Katherine S. Panageas,Richard D. Carvajal,Paul B. Chapman,Gary K. Schwartz,James P. Allison,James P. Allison,Jedd D. Wolchok +10 more
TL;DR: The authors report on advanced refractory melanoma patients treated in a compassionate use trial of ipilimumab at the Memorial Sloan‐Kettering Cancer Center.
Journal ArticleDOI
CTLA-4 and PD-1 Receptors Inhibit T-Cell Activation by Distinct Mechanisms.
Jens M. Chemnitz,James L. Riley,Kenneth A. Frauwirth,Inbal Braunstein,Sumire V. Kobayashi,Peter S. Linsley,Craig B. Thompson,Richard V. Parry +7 more
TL;DR: The data suggest that CTLA-4 and PD-1 inhibit T cell activation through distinct and potentially synergistic mechanisms.
Journal ArticleDOI
How to Use a Subgroup Analysis: Users’ Guide to the Medical Literature
TL;DR: 5 criteria to use when assessing the validity of subgroup analyses are provided, which will help clinicians deciding whether to use sub group analyses to guide their patient care.
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