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Melanoma and Cutaneous Malignancies

What Is the Role of Cytotoxic T Lymphocyte–Associated Antigen 4 Blockade in Patients with Metastatic Melanoma?

^aInstitute Gustave Roussy, Villejuif, France; ^bDepartment of Oncology, Dijon Hospital, Dijon, France

Key Words. Cytotoxic T lymphocyte–associated antigen 4 • Melanoma • Metastasis • Biomarkers

Correspondence: Caroline Robert, M.D., Ph.D., Dermatology Unit, Institute Gustave Roussy, 39 Rue Camille Desmoulins, 94805 Villejuif Cedex, France. Telephone: 33-1-42-11-42-10; Fax: 33-1-42-11-50-02; e-mail: caroline.robert{at}igr.fr

Received February 20, 2009; accepted for publication June 23, 2009; first published online in THE ONCOLOGIST Express on August 1, 2009.

Disclosures: Caroline Robert: Consultant/advisory role: Bayer, Pfizer, Bristol-Myers Squibb; Honoraria: Bayer, Pfizer, Bristol-Myers Squibb; Francois Ghiringhelli: None.

The article discusses unlabeled, investigational, or alternative use of a product, device or technique: tremelimumab (CP-675,206, Bristol-Myers Squibb) and ipilimumab (MDX-010, Pfizer) for metastatic melanoma.

The content of this article has been reviewed by independent peer reviewers to ensure that it is balanced, objective, and free from commercial bias. No financial relationships relevant to the content of this article have been disclosed by the independent peer reviewers.

With increasing knowledge of the molecular basis of the immune system and mechanisms of tumor tolerance, novel approaches to treating malignant diseases refractory to standard therapies are being investigated. Monoclonal antibodies (mAbs) that bind cytotoxic T lymphocyte–associated antigen (CTLA)-4 can block inhibitory signals normally generated through this receptor, thus prolonging and sustaining T-cell activation and proliferation. These antibodies are being developed and tested in patients with metastatic melanoma. This article reviews data published or presented at scientific congresses describing the clinical safety and antitumor activity of two different anti–CTLA-4 mAbs: tremelimumab (CP-675,206) and ipilimumab (MDX-010). Overall, although the response rate has not been consistently higher than the response rates associated with other treatments, the induction of durable responses and the favorable safety profile observed with anti–CTLA-4 mAbs are encouraging. However, the true advantage of these new drugs may depend largely on the characterization of predictive biomarkers of activity and subsequent targeting of responsive patients.