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Nat Rev Clin Oncol. 2016 Aug;13(8):473-86. doi: 10.1038/nrclinonc.2016.58. Epub 2016 May 4.

Safety profiles of anti-CTLA-4 and anti-PD-1 antibodies alone and in combination.

Author information

1
Dermatology Service, Department of Medicine, Gustave Roussy, 114 Rue Edouard Vaillant, 94805 Villejuif, France.
2
University of Pittsburgh, 4200 Fifth Avenue, Pittsburgh, Pennsylvania 15260, USA.
3
AP-HP, Internal Medicine Department, University Hospital of Bicêtre, 78 Rue du General Leclerc, 94270 Le Kremlin-Bicetre, France.
4
Paris Sud University, 63 Rue Gabriel Peri, 94270 Le Kremlin Bicêtre, France.
5
INSERM Unit U1184, 63 Rue Gabriel Peri, 94270 Le Kremlin Bicêtre, France.
6
Thoracic and Vascular Surgery Service, Centre Chirurgical Marie Lannelongue, 133 Avenue de la Resistance, 92350 Le Plessis-Robinson, France.
7
AP-HP, Department of Gastroenterology, University Hospital of Bicêtre, Paris Sud University, 78 Rue du General Leclerc, 94270 Le Kremlin-Bicetre, France.
8
Department of Nephrology, Pitié-Salpêtrière Hospital, 47-83 Boulevard de l'hopital, 75013 Paris, France.
9
Drug Development Department (DITEP), Gustave Roussy, 114 Rue Edouard Vaillant, 94805 Villejuif, France.
10
INSERM Unit U981, 114 Rue Edouard Vaillant, 94805 Villejuif, France.
11
Department of Nuclear Medicine and Endocrine Oncology, Gustave Roussy, 114 Rue Edouard Vaillant, 94805 Villejuif, France.
12
Biostatistic and Epidemiology Unit, Gustave Roussy, 114 Rue Edouard Vaillant, 94805 Villejuif, France.

Abstract

Inhibition of immune checkpoints using anti-programmed cell death-1 (PD-1) or anti cytotoxic-T-lymphocyte-associated antigen 4 (CTLA-4) monoclonal antibodies has revolutionized the management of patients with advanced-stage melanoma and is among the most promising treatment approaches for many other cancers. Use of CTLA-4 and PD-1 inhibitors, either as single agents, or in combination, has been approved by the US FDA for the treatment of metastatic melanoma. Treatment with these novel immunotherapies results in a unique and distinct spectrum of adverse events, which are mostly related to activation of the immune system and are, therefore, an unwanted consequence of their mechanisms of action. Adverse effects of CTLA-4 and/or PD-1 inhibition are most commonly observed in the skin, gastrointestinal tract, liver and endocrine systems and include pruritus, rash, nausea, diarrhoea and thyroid disorders. In this Review, the authors describe the adverse event profile of checkpoint inhibitors targeting CTLA-4 and PD-1, used both as monotherapies and in combination and aim to provide some general guidelines, based upon the mechanisms of action of these therapies and on the management of these immune-related adverse events.

PMID:
27141885
DOI:
10.1038/nrclinonc.2016.58
[Indexed for MEDLINE]
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