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2015 ; 3
(18
): 267
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Immune checkpoint inhibitors: therapeutic advances in melanoma
#MMPMID26605313
Márquez-Rodas I
; Cerezuela P
; Soria A
; Berrocal A
; Riso A
; González-Cao M
; Martín-Algarra S
Ann Transl Med
2015[Oct]; 3
(18
): 267
PMID26605313
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In recent years, new strategies for treating melanoma have been introduced,
improving the outlook for this challenging disease. One of the most important
advances has been the development of immunotherapy. The better understanding of
the role of the immunological system in tumor control has paved the way for
strategies to enhance the immune response against cancer cells. Monoclonal
antibodies (mAbs) against the immune checkpoints cytotoxic T-lymphocyte antigen-4
(CTLA-4) and programmed cell death protein 1 (PD-1) and its ligand (PD-L1) have
demonstrated high activity in melanoma and other tumors. Ipilimumab, an anti
CTLA-4 antibody, was the first drug of this class that was approved. Although the
response rate with ipilimumab is low (less than 20% of patients have objective
responses), 20% of patients have long survival, with similar results in the first
and second line settings. Nivolumab and pembrolizumab, both anti PD-1 inhibitors,
have been approved for the treatment of melanoma, with response rates of 40% and
a demonstrated survival advantage in phase III trials. This has marked a new era
in the treatment of metastatic melanoma and much research is now ongoing with
other drugs targeting checkpoint inhibitors. In addition, the agonist of
activating molecules on T cells and their combinations are being investigated.
Herein we review the clinical development of checkpoint inhibitors and their
approval for treatment of metastatic melanoma.
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