Efficacy and safety of ipilimumab monotherapy in patients with pretreated advanced melanoma: a multicenter single-arm phase II study

被引：406

作者：

O'Day, S. J. ^{[1
]}

Maio, M. ^{[2
]}

Chiarion-Sileni, V. ^{[3
]}

Gajewski, T. F. ^{[4
,5
]}

Pehamberger, H. ^{[6
]}

Bondarenko, I. N. ^{[7
]}

Queirolo, P. ^{[8
]}

Lundgren, L. ^{[9
]}

Mikhailov, S. ^{[10
]}

Roman, L. ^{[11
]}

Verschraegen, C. ^{[12
]}

Humphrey, R. ^{[13
]}

Ibrahim, R. ^{[13
]}

de Pril, V. ^{[14
]}

Hoos, A. ^{[13
]}

Wolchok, J. D. ^{[15
,16
]}

机构：

[1] Angeles Clin & Res Inst, Santa Monica, CA 90404 USA

[2] Univ Hosp Siena, Div Med Oncol & Immunotherapy, Dept Oncol, Ist Toscano Tumori, Siena, Italy

[3] IOV IRCCS, Melanoma & Skin Canc Unit, Padua, Italy

[4] Univ Chicago, Dept Pathol, Chicago, IL 60637 USA

[5] Univ Chicago, Dept Med, Chicago, IL 60637 USA

[6] Med Univ Vienna, Dept Dermatol, Vienna, Austria

[7] Dnepropetrovsk State Med Acad, Dnepropetrovsk, Ukraine

[8] Natl Inst Canc Res, Dept Med Oncol A, Genoa, Italy

[9] Univ Lund Hosp, Dept Oncol, S-22185 Lund, Sweden

[10] Stavropol Reg Clin Oncol Ctr, Stavropol, Russia

[11] Leningrad Reg Oncol Ctr, St Petersburg, Russia

[12] Univ New Mexico, Ctr Canc, Albuquerque, NM 87131 USA

[13] Bristol Myers Squibb Co, Wallingford, CT 06492 USA

[14] Bristol Myers Squibb Co, Braine Lalleud, Belgium

[15] Mem Sloan Kettering Canc Ctr, Dept Med, New York, NY 10021 USA

[16] Mem Sloan Kettering Canc Ctr, Ludwig Ctr Canc Immunotherapy, New York, NY 10021 USA

来源：

ANNALS OF ONCOLOGY | 2010年 / 21卷 / 08期

关键词：

cytotoxic T-lymphocyte antigen-4; immunotherapy; ipilimumab; metastatic melanoma; phase II clinical trial; UNRESECTABLE STAGE-III; METASTATIC MELANOMA; ANTI-CTLA-4; ANTIBODY; ANTIGEN-4; PROGNOSTIC-FACTORS; CLINICAL-RESPONSE; TUMOR-REGRESSION; AUTOIMMUNITY; CONFIDENCE; SURVIVAL;

D O I：

10.1093/annonc/mdq013

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Background: This phase II study evaluated the safety and activity of ipilimumab, a fully human mAb that blocks cytotoxic T-lymphocyte antigen-4, in patients with advanced melanoma. Patients and methods: Patients with previously treated, unresectable stage III/stage IV melanoma received 10 mg/kg ipilimumab every 3 weeks for four cycles (induction) followed by maintenance therapy every 3 months. The primary end point was best overall response rate (BORR) using modified World Health Organization (WHO) criteria. We also carried out an exploratory analysis of proposed immune-related response criteria (irRC). Results: BORR was 5.8% with a disease control rate (DCR) of 27% (N = 155). One-and 2-year survival rates (95% confidence interval) were 47.2% (39.5% to 55.1%) and 32.8% (25.4% to 40.5%), respectively, with a median overall survival of 10.2 months (7.6-16.3). Of 43 patients with disease progression by modified WHO criteria, 12 had disease control by irRC (8% of all treated patients), resulting in a total DCR of 35%. Adverse events (AEs) were largely immune related, occurring mainly in the skin and gastrointestinal tract, with 19% grade 3 and 3.2% grade 4. Immune-related AEs were manageable and generally reversible with corticosteroids. Conclusion: Ipilimumab demonstrated clinical activity with encouraging long-term survival in a previously treated advanced melanoma population.

引用

页码：1712 / 1717

页数：6

共 32 条

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