Open-label, multicenter, single-arm phase II DeCOG-study of ipilimumab in pretreated patients with different subtypes of metastatic melanoma

Journal of Translational Medicine

Research

Michael Fluck¹  Carola Berking²  Felix Kiecker³  Claus Garbe⁴  Zeinab Assi⁴  Thomas K. Eigentler⁴  Rainer Rompel⁵  Eckhart Kämpgen⁶  Peter Mohr⁷  Edgar Dippel⁸  Rudolf Stadler⁹  Dirk Schadendorf^1,10  Lisa Zimmer^1,10  Carmen Loquai^1,11  Patrick Terheyden^1,12  Jan Simon^1,13  Jochen Utikal^1,14  Axel Hauschild^1,15 

[1] Department of Dermatology Hornheide, Münster, Germany;Department of Dermatology and Allergy, Ludwig-Maximilian University, Munich, Germany;Department of Dermatology and Allergy, Skin Cancer Center, Charité-Universitätsmedizin Berlin, Berlin, Germany;Department of Dermatology, Center for Dermatooncology, University Medical Center Tübingen, Tübingen, Germany;Department of Dermatology, Clinical Centre Kassel, Kassel, Germany;Department of Dermatology, Dermatologikum Berlin, Berlin, Germany;Department of Dermatology, Elbekliniken Stade Buxtehude, Buxtehude, Germany;Department of Dermatology, Klinikum Ludwigshafen, Skin Cancer Center Rheinpfalz, Ludwigshafen, Germany;Department of Dermatology, Medical Centre Minden, Minden, Germany;Department of Dermatology, University Hospital, University Duisburg-Essen, Essen, Germany;Department of Dermatology, University Medical Center, Johannes Gutenberg-University, Mainz, Germany;Department of Dermatology, University of Lübeck, Lübeck, Germany;Department of Dermatology, Venereology and Allergology, University Hospital Leipzig, Germany, Leipzig;Skin Cancer Unit, German Cancer Research Center (DKFZ), Heidelberg, Germany;Department of Dermatology, Venereology and Allergology, University Medical Center Mannheim, Ruprecht-Karl University of Heidelberg, Mannheim, Germany;University Department of Dermatology, Kiel, Germany;

关键词: Phase II;    Melanoma;    Cutaneous melanoma;    Mucosal melanoma;    Occult melanoma;    Ipilimumab;    Anti-CTLA-4;   

DOI  :  10.1186/s12967-015-0716-5

 received in 2015-07-03, accepted in 2015-10-26,  发布年份 2015

来源: Springer

【 摘 要 】

BackgroundIpilimumab is an approved immunotherapy that has shown an overall survival benefit in patients with cutaneous metastatic melanoma in two phase III trials. As results of registrational trials might not answer all questions regarding safety and efficacy of ipilimumab in patients with advanced melanoma seen in daily clinical practice, the Dermatologic Cooperative Oncology Group conducted a phase II study to assess the efficacy and safety of ipilimumab in patients with different subtypes of metastatic melanoma.Patients and methodsWe undertook a multicenter phase II study in melanoma patients irrespective of location of the primary melanoma. Here we present data on patients with pretreated metastatic cutaneous, mucosal and occult melanoma who received up to four cycles of ipilimumab administered at a dose of 3 mg/kg in 3 week intervals. Tumor assessments were conducted at baseline, weeks 12, 24, 36 and 48 according to RECIST 1.1 criteria. Adverse events (AEs), including immune-related AEs were graded according to National Cancer Institute Common Toxicity Criteria (CTC) v.4.0. Primary endpoint was the OS rate at 12 months.Results103 pretreated patients received at least one dose of ipilimumab, including 83 cutaneous, seven mucosal and 13 occult melanomas. 1-year OS rates for cutaneous, mucosal and occult melanoma were 38 %, 14 % and 27 %, respectively. Median OS was 6.8 months (95 % CI 5.3–9.9) for cutaneous, 9.6 months (95 % CI 1.6–11.1) for mucosal, and 9.9 months (lower 95 % CI 2.3, upper 95 % CI non-existent) for occult melanoma. Overall response rates for cutaneous, mucosal and occult melanoma were 16 %, 17 % and 11 %, respectively. Eleven patients had partial response (16 %) and ten patients experienced stable disease (14 %), none achieved a complete response. Treatment-related AEs were observed in 71 patients (69 %), including 20 grade 3–4 events (19 %). No new and unexpected safety findings were noted.ConclusionsIpilimumab is a treatment option for pretreated patients with advanced cutaneous melanoma seen in daily routine. Toxicity was manageable when treated as per protocol-specific guidelines.Trial registration: Clinical Trials.gov NCT01355120

【 授权许可】

CC BY   
© Zimmer et al. 2015