Axel Hauschild

9031 Background: Ipilimumab is a recently approved immunotherapy that has shown an overall survival benefit in previously treated and treatment-naïve patients with metastatic melanoma in two phase III trials. However, results of registrational trials might not address all questions regarding safety and efficacy of ipilimumab in advanced melanoma patients seen in daily routine. We performed a multicenter, phase II clinical trial of ipilimumab in patients with different subtypes of metastatic melanoma. Methods: Pretreated patients with unresectable stage III or stage IV with cutaneous, mucosal, ocular or unknown primary melanoma (MUP) were included into this study (CA184-137; supported by BMS). Treatment-naïve patients with metastatic ocular melanoma were eligible, too. Four cycles ipilimumab should be administered at a dose of 3 mg/kg 3 weeks apart. Tumor assessments according to RECIST 1.1 version were conducted at baseline, weeks 12, 24, 36 and 48. Adverse events (AEs), including immune-related AEs were graded according to National Cancer Institute Common Toxicity Criteria v.4.0. Primary endpoint was the overall survival (OS) rate at 12 months. Results: Between May 2011 to December 2013, 156 patients were enrolled in 25 German centers and received at least one dose of ipilimumab, including 83 cutaneous, 7 mucosal, 53 ocular melanomas and 13 MUP. After a median follow-up of 7 months (range 0.1-26.4), 12-month OS rates were 37% for cutaneous, 14% for mucosal, and 22% for ocular melanomas and 27% for MUP. The median OS from the first dose of ipilimumab was 6.9 months (95% CI 5.7-8.1). The overall response rates among 104 evaluable patients were 16% for cutaneous, 17% for mucosal, 9% for ocular melanomas and 11% for MUP. There were one patient with complete response (1%), 13 patients with partial response (13%), and 23 patients with stable disease (22%). Treatment-related AEs were observed in 106 patients (68%), including 39 grade 3-4 events (25%). There was a drug-related death due to pancytopenia. Conclusions: Ipilimumab is a treatment option for patients with cutaneous, ocular, mucosal and unknown primary melanoma with manageable toxicity. Clinical trial information: NCT01355120.

BACKGROUND.: Dacarbazine (DTIC) and pegylated interferon (IFN)–α‐2a have both demonstrated some efficacy as single agents in metastatic melanoma. To the authors' knowledge, the current study is the first to test a combination of these 2 agents in a phase 2 trial.METHODS.: Twenty–eight patients with stage IV melanoma without brain metastases were treated with DTIC (at a dose of 850 mg/m² every 3 weeks) combined with weekly pegylated IFN–α‐2a at a dose of 180 μg. The study was initiated to evaluate the efficacy and tolerability of the combination. The primary study endpoint was objective response.RESULTS.: Twenty–five patients were evaluable for response. Two patients (8.0%) achieved a complete response that continued for >480 days and 746 days, respectively. Four patients (16.0%) demonstrated a partial response, and another patient experienced stable disease. Six of 7 nonprogressive patients had either not received treatment or had not developed disease progression during adjuvant IFN treatment for stage II/III disease. The median duration of response was 236 days, the median progression‐free survival was 56 days, and the overall survival time was 403 days. Few grade 3 toxicities and only 1 grade 4 toxicity were observed (according to National Cancer Institute Common Toxicity Criteria).CONCLUSIONS.: The combination of DTIC and pegylated IFN–α‐2a was found to be well tolerated in patients with metastatic melanoma. The response rate of 24%, including 2 long‐lasting complete responses, is encouraging, but must be confirmed in larger trials. Cancer 2008. © 2008 American Cancer Society.

Summary: In the treatment of malignant melanoma, various stage‐dependent diagnostic and therapeutic procedures are widely accepted.The situation becomes more complicated in pregnant women due to potential hazardous side effects to the fetus. We report on a 36‐year‐old woman, who was admitted with a high‐risk malignant melanoma on the right cheek. Prior to surgery we performed computed tomography (CT)‐scans that were unremarkable with the exception of “two small cysts of the uterus” The primary melanoma was excised and a sentinel node biopsy was performed under general anesthesia using radioactive tracers. Afterwards, adjuvant therapy with interferon alpha 2b was initiated. Five weeks later our patient reported that she was pregnant with twins in their eleventh week of gestation, although she previously denied several questions regarding a potential pregnancy. She declined the offer of an abortion and elected to continue with the interferon treatment against our medical advice. In the 36^th week of gestation, she developed regional lymph node metastases. Consequently, labor was induced, resulting in the delivery of healthy twins. Six months later our patient developed lung metastases. Despite several chemotherapy regimens, she died one year later. An interdisciplinary approach to obtaining informed consent and managing female high risk melanoma patients with potential or present pregnancy is presented.

We describe a 50‐year‐old female patient who developed extensive lymphomatous infiltrates on her forehead, scalp and face within a few months. Histology and immunohistochemistry of skin tumours revea...

Summary We report an 80‐year‐old man suffering from an angiosarcoma of the scalp. Because of the wide extent of the lesions, surgery was not performed. Instead, the patient was treated with electron‐...