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Eur J Cancer. 2015 Nov;51(17):2689-97. doi: 10.1016/j.ejca.2015.08.012. Epub 2015 Sep 10.

Long term survival with cytotoxic T lymphocyte-associated antigen 4 blockade using tremelimumab.

Author information

1
Department of Medical Oncology, City of Hope National Medical Center, Duarte, CA, USA.
2
Department of Melanoma Medical Oncology, The University of Texas-MD Anderson Cancer Center, Houston, TX, USA.
3
Department of Medicine Statistics Core, University of California Los Angeles, Los Angeles, CA, USA.
4
St. Luke's Medical Center Cancer Center, Houston, TX, USA.
5
Department of Medicine, Division of Hematology/Oncology, Jonsson Comprehensive Cancer Center at UCLA, Los Angeles, CA, USA.
6
Department of Radiology, University of California Los Angeles, Los Angeles, CA, USA.
7
Department of Melanoma Medical Oncology, The University of Texas-MD Anderson Cancer Center, Houston, TX, USA; California Pacific Medical Center, San Francisco, CA, USA.
8
Department of Medicine, Division of Hematology/Oncology, Jonsson Comprehensive Cancer Center at UCLA, Los Angeles, CA, USA. Electronic address: aribas@mednet.ucla.edu.

Abstract

PURPOSE:

One of the hallmarks of cancer immunotherapy is the long duration of responses, evident with cytokines like interleukin-2 or a variety of cancer vaccines. However, there is limited information available on very long term outcomes of patients treated with anti-cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) antibodies. Tremelimumab is an anti-CTLA-4 antibody of immunoglobulin G2 (IgG2) isotype initially tested in patients with advanced melanoma over 12 years ago.

METHODS:

We reviewed the outcomes of patients with advanced melanoma enrolled in four phase 1 and 2 tremelimumab trials at two sites to determine response rates and long-term survival.

RESULTS:

A total of 143 patients were enrolled at two institutions from 2002 to 2008. Tremelimumab administration varied between a single dose of 0.01 mg/kg and 15 mg/kg every 3 months. Median overall survival was 13 months (95% confidence interval (CI), 10-16.6), ranging from less than a month to 12+ years. An objective response rate of 15.6% was observed, with median duration of response of 6.5 years, range of 3-136+ months. The Kaplan-Meier estimated 5 year survival rate was 20% (95% CI, 13-26%), with 10 and 12.5 year survival rates of 16% (95% CI, 9-23%).

CONCLUSIONS:

CTLA-4 blockade with tremelimumab can lead to very long duration of objective anti-tumour responses beyond 12 years.

KEYWORDS:

Anti-CTLA-4 therapy; Immunotherapy; Melanoma; Tremelimumab

Comment in

PMID:
26364516
PMCID:
PMC4821004
DOI:
10.1016/j.ejca.2015.08.012
[Indexed for MEDLINE]
Free PMC Article

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