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Melanoma: HELP
Articles by Carmen Loquai
Based on 56 articles published since 2008
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Between 2008 and 2019, C. Loquai wrote the following 56 articles about Melanoma.
 
+ Citations + Abstracts
Pages: 1 · 2 · 3
1 Guideline S3-guideline "diagnosis, therapy and follow-up of melanoma" -- short version. 2013

Pflugfelder, Annette / Kochs, Corinna / Blum, Andreas / Capellaro, Marcus / Czeschik, Christina / Dettenborn, Therese / Dill, Dorothee / Dippel, Edgar / Eigentler, Thomas / Feyer, Petra / Follmann, Markus / Frerich, Bernhard / Ganten, Maria-Katharina / Gärtner, Jan / Gutzmer, Ralf / Hassel, Jessica / Hauschild, Axel / Hohenberger, Peter / Hübner, Jutta / Kaatz, Martin / Kleeberg, Ulrich R / Kölbl, Oliver / Kortmann, Rolf-Dieter / Krause-Bergmann, Albrecht / Kurschat, Peter / Leiter, Ulrike / Link, Hartmut / Loquai, Carmen / Löser, Christoph / Mackensen, Andreas / Meier, Friedegund / Mohr, Peter / Möhrle, Matthias / Nashan, Dorothee / Reske, Sven / Rose, Christian / Sander, Christian / Satzger, Imke / Schiller, Meinhard / Schlemmer, Heinz-Peter / Strittmatter, Gerhard / Sunderkötter, Cord / Swoboda, Lothar / Trefzer, Uwe / Voltz, Raymond / Vordermark, Dirk / Weichenthal, Michael / Werner, Andreas / Wesselmann, Simone / Weyergraf, Ansgar J / Wick, Wolfgang / Garbe, Claus / Schadendorf, Dirk / Anonymous5740759. ·Department of Dermatology, University Hospital Tübingen, Germany. ·J Dtsch Dermatol Ges · Pubmed #23721604.

ABSTRACT: -- No abstract --

2 Review Radiotherapy with BRAF inhibitor therapy for melanoma: progress and possibilities. 2016

Zahnreich, Sebastian / Mayer, Arnulf / Loquai, Carmen / Grabbe, Stephan / Schmidberger, Heinz. ·Department of Radiation Oncology & Radiotherapy, University Medical Center Johannes Gutenberg University Mainz, Germany. · Department of Dermatology, University Medical Center Johannes Gutenberg University Mainz, Germany. ·Future Oncol · Pubmed #26616061.

ABSTRACT: The introduction of small molecule BRAF(V600) kinase inhibitors represents a milestone in the targeted therapy of patients with metastatic melanoma by a significant increase in therapeutic efficacy in terms of overall and progression-free survival compared with conventional chemotherapy. Beside BRAF(V600) inhibitor treatment, radiotherapy is a further mainstay for the therapy of metastatic melanoma and thus a concomitant or sequential application of BRAF(V600) inhibitors and radiotherapy is inevitable. Recent reports show a significant radiosensitization of the irradiated healthy tissue in patients with melanoma after the combination of radiotherapy and BRAF(V600) inhibitors, evoking concern in clinical practice. We review interactions of BRAF(V600) inhibitors and radiation with regard to antitumor effects and an increased radiotoxicity in the healthy tissue.

3 Clinical Trial Encorafenib plus binimetinib versus vemurafenib or encorafenib in patients with BRAF-mutant melanoma (COLUMBUS): a multicentre, open-label, randomised phase 3 trial. 2018

Dummer, Reinhard / Ascierto, Paolo A / Gogas, Helen J / Arance, Ana / Mandala, Mario / Liszkay, Gabriella / Garbe, Claus / Schadendorf, Dirk / Krajsova, Ivana / Gutzmer, Ralf / Chiarion-Sileni, Vanna / Dutriaux, Caroline / de Groot, Jan Willem B / Yamazaki, Naoya / Loquai, Carmen / Moutouh-de Parseval, Laure A / Pickard, Michael D / Sandor, Victor / Robert, Caroline / Flaherty, Keith T. ·Department of Dermatology, University Hospital Zürich Skin Cancer Center, Zürich, Switzerland. Electronic address: reinhard.dummer@usz.ch. · Melanoma Unit, Cancer Immunotherapy and Innovative Therapies, Istituto Nazionale Tumori IRCCS Fondazione Pascale, Naples, Italy. · Department of Internal Medicine, National and Kapodistrian University of Athens, Laikon Hospital, Athens, Greece. · Department of Medical Oncology, Hospital Clinic of Barcelona, Barcelona, Spain. · Department of Oncology and Haematology, Papa Giovanni XXIII Cancer Center Hospital, Bergamo, Italy. · Department of Dermatology, National Institute of Oncology, Budapest, Hungary. · Department of Dermatology, University Hospital Tüebingen, Tüebingen, Germany. · Department of Dermatology, University Hospital Essen, Essen, Germany; German Cancer Consortium, Heidelberg, Germany. · Department of Dermato-oncology, University Hospital Prague, Charles University First Medical Faculty, Prague, Czech Republic. · Department of Dermatology and Allergy, Skin Cancer Center Hannover, Hannover Medical School, Hannover, Germany. · Melanoma Cancer Unit, Oncology Institute of Veneto IRCCS, Padua, Italy. · Department of Oncologic Dermatology, Centre Hospitalier Universitaire de Bordeaux, Hôpital Saint-André, Bordeaux, France. · Department of Medical Oncology, Isala, Zwolle, Netherlands. · Department of Dermatologic Oncology, National Cancer Center Hospital, Tokyo, Japan. · Department of Dermatology, University Medical Center Mainz, Mainz, Germany. · Translational Clinical Oncology, Novartis Pharma AG, Basel, Switzerland. · Array BioPharma, Boulder, CO, USA. · Service of Dermatology, Department of Medicine, Paris-Sud University, Gustave Roussy, Villejuif, France. · Cancer Center, Massachusetts General Hospital, Boston, MA, USA. ·Lancet Oncol · Pubmed #29573941.

ABSTRACT: BACKGROUND: Combined BRAF-MEK inhibitor therapy is the standard of care for BRAF METHODS: COLUMBUS was conducted as a two-part, randomised, open-label phase 3 study at 162 hospitals in 28 countries. Eligible patients were aged 18 years or older and had histologically confirmed locally advanced (American Joint Committee on Cancer [AJCC] stage IIIB, IIIC, or IV), unresectable or metastatic cutaneous melanoma, or unknown primary melanoma; a BRAF FINDINGS: Between Dec 30, 2013, and April 10, 2015, 577 of 1345 screened patients were randomly assigned to either the encorafenib plus binimetinib group (n=192), the encorafenib group (n=194), or the vemurafenib group (n=191). With a median follow-up of 16·6 months (95% CI 14·8-16·9), median progression-free survival was 14·9 months (95% CI 11·0-18·5) in the encorafenib plus binimetinib group and 7·3 months (5·6-8·2) in the vemurafenib group (hazard ratio [HR] 0·54, 95% CI 0·41-0·71; two-sided p<0·0001). The most common grade 3-4 adverse events seen in more than 5% of patients in the encorafenib plus binimetinib group were increased γ-glutamyltransferase (18 [9%] of 192 patients), increased creatine phosphokinase (13 [7%]), and hypertension (11 [6%]); in the encorafenib group they were palmoplantar erythrodysaesthesia syndrome (26 [14%] of 192 patients), myalgia (19 [10%]), and arthralgia (18 [9%]); and in the vemurafenib group it was arthralgia (11 [6%] of 186 patients). There were no treatment-related deaths except for one death in the combination group, which was considered possibly related to treatment by the investigator. INTERPRETATION: Encorafenib plus binimetinib and encorafenib monotherapy showed favourable efficacy compared with vemurafenib. Overall, encorafenib plus binimetinib appears to have an improved tolerability profile compared with encorafenib or vemurafenib. Encorafenib plus binimetinib could represent a new treatment option for patients with BRAF-mutant melanoma. FUNDING: Array BioPharma, Novartis.

4 Clinical Trial Ipilimumab 10 mg/kg versus ipilimumab 3 mg/kg in patients with unresectable or metastatic melanoma: a randomised, double-blind, multicentre, phase 3 trial. 2017

Ascierto, Paolo A / Del Vecchio, Michele / Robert, Caroline / Mackiewicz, Andrzej / Chiarion-Sileni, Vanna / Arance, Ana / Lebbé, Céleste / Bastholt, Lars / Hamid, Omid / Rutkowski, Piotr / McNeil, Catriona / Garbe, Claus / Loquai, Carmen / Dreno, Brigitte / Thomas, Luc / Grob, Jean-Jacques / Liszkay, Gabriella / Nyakas, Marta / Gutzmer, Ralf / Pikiel, Joanna / Grange, Florent / Hoeller, Christoph / Ferraresi, Virginia / Smylie, Michael / Schadendorf, Dirk / Mortier, Laurent / Svane, Inge Marie / Hennicken, Delphine / Qureshi, Anila / Maio, Michele. ·Istituto Nazionale Tumori Fondazione Pascale, Naples, Italy. Electronic address: paolo.ascierto@gmail.com. · Medical Oncology, National Cancer Institute, Milan, Italy. · Gustave Roussy Cancer Campus Grand Paris, Villejuif, France. · Department of Diagnostics and Cancer Immunology, Greater Poland Cancer Centre, Poznan Medical University, Poznan, Poland. · IOV-IRCCS, Melanoma Oncology Unit, Padova, Italy. · Hospital Clinic and Institut d'Investigacions Biomèdiques August Pi I Sunyer, Barcelona, Spain. · AP-HP Dermatology CIC Departments, Saint-Louis Hospital, INSERM U976, Université Paris Diderot, Paris, France. · Odense University Hospital, Odense, Denmark. · The Angeles Clinic and Research Institute, Los Angeles, CA, USA. · Maria Sklodowska-Curie Memorial Cancer Center, Warsaw, Poland. · Chris O'Brien Lifehouse and Royal Prince Alfred Hospital, Camperdown, NSW, Australia; Melanoma Institute Australia, Sydney, NSW, Australia. · Eberhard Karls University, Tübingen, Germany. · University Medical Center, Mainz, Germany. · Department of Oncodermatology, INSERM Research Unit 892, Nantes University Hospital, Nantes, France. · Department of Dermatology, Centre Hospitalier Lyon-Sud, Pierre-Bénite, France. · Hospital de la Timone, Marseille, France. · National Institute of Oncology, Budapest, Hungary. · Oslo University Hospital, Oslo, Norway. · Medizinische Hochschule Hannover, Hannover, Germany. · Wojewodzkie Centrum Oncologii, Gdańsk, Poland. · Department of Dermatology, Reims University Hospital, Reims, France. · Medical University of Vienna, Vienna, Austria. · Istituti Fisioterapici Ospitalieri, Rome, Italy. · Cross Cancer Institute, Edmonton, AB, Canada. · University Hospital Essen, Essen, Germany. · Hôspital Claude Huriez, Lille, France. · Herlev Hospital, University of Copenhagen, Herlev, Denmark. · Bristol-Myers Squibb, Princeton, NJ, USA. · University Hospital of Siena, Istituto Toscano Tumori, Siena, Italy. ·Lancet Oncol · Pubmed #28359784.

ABSTRACT: BACKGROUND: A phase 2 trial suggested increased overall survival and increased incidence of treatment-related grade 3-4 adverse events with ipilimumab 10 mg/kg compared with ipilimumab 3 mg/kg in patients with advanced melanoma. We report a phase 3 trial comparing the benefit-risk profile of ipilimumab 10 mg/kg versus 3 mg/kg. METHODS: This randomised, double-blind, multicentre, phase 3 trial was done in 87 centres in 21 countries worldwide. Patients with untreated or previously treated unresectable stage III or IV melanoma, without previous treatment with BRAF inhibitors or immune checkpoint inhibitors, were randomly assigned (1:1) with an interactive voice response system by the permuted block method using block size 4 to ipilimumab 10 mg/kg or 3 mg/kg, administered by intravenous infusion for 90 min every 3 weeks for four doses. Patients were stratified by metastasis stage, previous treatment for metastatic melanoma, and Eastern Cooperative Oncology Group performance status. The patients, investigators, and site staff were masked to treatment assignment. The primary endpoint was overall survival in the intention-to-treat population and safety was assessed in all patients who received at least one dose of study treatment. This study is completed and was registered with ClinicalTrials.gov, number NCT01515189. FINDINGS: Between Feb 29, and July 9, 2012, 727 patients were enrolled and randomly assigned to ipilimumab 10 mg/kg (365 patients; 364 treated) or ipilimumab 3 mg/kg (362 patients; all treated). Median follow-up was 14·5 months (IQR 4·6-42·3) for the ipilimumab 10 mg/kg group and 11·2 months (4·9-29·4) for the ipilimumab 3 mg/kg group. Median overall survival was 15·7 months (95% CI 11·6-17·8) for ipilimumab 10 mg/kg compared with 11·5 months (9·9-13·3) for ipilimumab 3 mg/kg (hazard ratio 0·84, 95% CI 0·70-0·99; p=0·04). The most common grade 3-4 treatment-related adverse events were diarrhoea (37 [10%] of 364 patients in the 10 mg/kg group vs 21 [6%] of 362 patients in the 3 mg/kg group), colitis (19 [5%] vs nine [2%]), increased alanine aminotransferase (12 [3%] vs two [1%]), and hypophysitis (ten [3%] vs seven [2%]). Treatment-related serious adverse events were reported in 133 (37%) patients in the 10 mg/kg group and 66 (18%) patients in the 3 mg/kg group; four (1%) versus two (<1%) patients died from treatment-related adverse events. INTERPRETATION: In patients with advanced melanoma, ipilimumab 10 mg/kg resulted in significantly longer overall survival than did ipilimumab 3 mg/kg, but with increased treatment-related adverse events. Although the treatment landscape for advanced melanoma has changed since this study was initiated, the clinical use of ipilimumab in refractory patients with unmet medical needs could warrant further assessment. FUNDING: Bristol-Myers Squibb.

5 Clinical Trial Ipilimumab alone or in combination with nivolumab after progression on anti-PD-1 therapy in advanced melanoma. 2017

Zimmer, Lisa / Apuri, Susmitha / Eroglu, Zeynep / Kottschade, Lisa A / Forschner, Andrea / Gutzmer, Ralf / Schlaak, Max / Heinzerling, Lucie / Krackhardt, Angela M / Loquai, Carmen / Markovic, Svetomir N / Joseph, Richard W / Markey, Kelly / Utikal, Jochen S / Weishaupt, Carsten / Goldinger, Simone M / Sondak, Vernon K / Zager, Jonathan S / Schadendorf, Dirk / Khushalani, Nikhil I. ·Department of Dermatology, University Hospital, University Duisburg-Essen, Germany & German Cancer Consortium (DKTK), Heidelberg, Germany. Electronic address: lisa.zimmer@uk-essen.de. · Hematology/Oncology Fellowship Program, H Lee Moffitt Cancer Center and Research Institute/University of South Florida, Tampa, FL, USA. · Department of Cutaneous Oncology, Moffitt Cancer Center, Tampa, FL, USA. · Department of Oncology, Hematology and Immunology, Mayo Clinic, Rochester, MN, USA. · Department of Dermatology, University Hospital Tübingen, Germany. · Department of Dermatology and Allergy, Skin Cancer Center Hannover, Hannover Medical School, Germany. · Department of Dermatology, University Hospital Cologne, Skin Cancer Center, Center for Integrated Oncology (CIO) Köln Bonn, Germany. · Department of Dermatology, University Hospital Erlangen, Friedrich-Alexander-University Erlangen-Nürnberg (FAU), Germany. · III. Medical Department, Technische Universität München (TUM) Munich, Germany. · Department of Dermatology, University Hospital Mainz, Germany. · 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. · Department of Dermatology, University Hospital Münster, Germany. · Department of Dermatology, University Hospital Zurich, Switzerland. · Department of Dermatology, University Hospital, University Duisburg-Essen, Germany & German Cancer Consortium (DKTK), Heidelberg, Germany. ·Eur J Cancer · Pubmed #28214657.

ABSTRACT: BACKGROUND: The anti-programmed cell death-1 (PD-1) inhibitors pembrolizumab and nivolumab alone or in combination with ipilimumab have shown improved objective response rates and progression-free survival compared to ipilimumab only in advanced melanoma patients. Anti-PD-1 therapy demonstrated nearly equal clinical efficacy in patients who had progressed after ipilimumab or were treatment-naïve. However, only limited evidence exists regarding the efficacy of ipilimumab alone or in combination with nivolumab after treatment failure to anti-PD-therapy. PATIENTS AND METHODS: A multicenter retrospective study in advanced melanoma patients who were treated with nivolumab (1 or 3 mg/kg) and ipilimumab (1 mg or 3 mg/kg) or ipilimumab (3 mg/kg) alone after treatment failure to anti-PD-1 therapy was performed. Patient, tumour, pre- and post-treatment characteristics were analysed. RESULTS: In total, 47 patients were treated with ipilimumab (ipi-group) and 37 patients with ipilimumab and nivolumab (combination-group) after treatment failure to anti-PD-1 therapy. Overall response rates for the ipi- and the combination-group were 16% and 21%, respectively. Disease control rate was 42% for the ipi-group and 33% for the combination-group. One-year overall survival rates for the ipi- and the combination-group were 54% and 55%, respectively. CONCLUSIONS: Ipilimumab should be considered as a viable treatment option for patients with failure to prior anti-PD-1 therapy, including those with progressive disease as best response to prior anti-PD-1. In contrast, the combination of ipilimumab and nivolumab appears significantly less effective in this setting compared to treatment-naïve patients.

6 Clinical Trial Health-related quality of life in the randomised KEYNOTE-002 study of pembrolizumab versus chemotherapy in patients with ipilimumab-refractory melanoma. 2016

Schadendorf, Dirk / Dummer, Reinhard / Hauschild, Axel / Robert, Caroline / Hamid, Omid / Daud, Adil / van den Eertwegh, Alfons / Cranmer, Lee / O'Day, Steven / Puzanov, Igor / Schachter, Jacob / Blank, Christian / Salama, April / Loquai, Carmen / Mehnert, Janice M / Hille, Darcy / Ebbinghaus, Scot / Kang, S Peter / Zhou, Wei / Ribas, Antoni. ·University Hospital Essen, Hufelandstrasse 55, D-45147 Essen, Germany. Electronic address: dirk.schadendorf@uk-essen.de. · Department of Dermatology, University Hospital Zurich, Gloriastrasse 31, 8091 Zurich, Switzerland. Electronic address: Reinhard.Dummer@usz.ch. · Department of Dermatology, Venereology, and Allergology, University Hospital Schleswig-Holstein, Kiel Campus, Arnold-Heller Strasse 3, 24105 Kiel, Germany. Electronic address: ahauschild@dermatology.uni-kiel.de. · Gustave Roussy Cancer Campus and Paris-Sud University, 114 Rue Edouard Vaillant, 94800 Villejuif, France. Electronic address: Caroline.Robert@gustaveroussyr.fr. · The Angeles Clinic and Research Institute, 2001 Santa Monica Blvd, Ste 560W, Santa Monica, CA 90404, USA. Electronic address: ohamid@theangelesclinic.org. · University of California, San Francisco School of Medicine, 1600 Divisadero St, NZ Bldg A, San Francisco, CA 94115, USA. Electronic address: Adil.Daud@ucsf.edu. · Department of Medical Oncology, VU University Medical Center Amsterdam, De Boelelaan 1118, 1081 HZ Amsterdam, The Netherlands. Electronic address: vandeneertwegh@VUMC.nl. · Department of Hematology/Oncology, University of Arizona Cancer Center at UMC North, 3838 N. Campbell Ave, Tucson, AZ 85724, USA. Electronic address: lcranmer@uacc.arizona.edu. · The Los Angeles Skin Cancer Institute, The Beverly Hills Cancer Center, 8900 Wilshire Blvd, Beverly Hills, CA 90211, USA. Electronic address: stevenjoday@gmail.com. · Vanderbilt-Ingram Cancer Center, 2220 Pierce Ave, 777 Preston Research Building, Nashville, TN 37232, USA. Electronic address: igor.puzanov@vanderbilt.edu. · Department of Oncology, Ella Institute for Melanoma, Sheba Medical Center, Derech Sheba 2, Tel-Hashomer, Ramat-Gan, Israel. Electronic address: Jacob.Schachter@sheba.health.gov.il. · Department of Medical Oncology, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands. Electronic address: c.blank@nki.nl. · Division of Medical Oncology, Duke Cancer Institute, Duke University Medical Center, Box 3198, 20 Duke Medicine Circle, Durham, NC 27710, USA. Electronic address: april.salama@duke.edu. · Skin Clinic, Universitätsmedizin Mainz, Langenbeckstrasse 1, 55131 Mainz, Germany. Electronic address: carmen.loquai@unimedizin-mainz.de. · Rutgers Cancer Institute of New Jersey, 195 Little Albany Street, New Brunswick, NJ 08901, USA. Electronic address: mehnerja@cinj.rutgers.edu. · Merck & Co., Inc., 2000 Galloping Hill Road, Kenilworth, NJ 07033, USA. Electronic address: darcy_hille@merck.com. · Merck & Co., Inc., 2000 Galloping Hill Road, Kenilworth, NJ 07033, USA. Electronic address: scot_ebbinghaus@merck.com. · Merck & Co., Inc., 2000 Galloping Hill Road, Kenilworth, NJ 07033, USA. Electronic address: s.peter.kang@merck.com. · Merck & Co., Inc., 2000 Galloping Hill Road, Kenilworth, NJ 07033, USA. Electronic address: wei.zhou2@merck.com. · Department of Medicine, Division of Hematology-Oncology, Jonsson Comprehensive Cancer Center (JCCC) at the University of California, Los Angeles (UCLA), 10833 Le Conte Ave, Los Angeles, CA 90095, USA. Electronic address: aribas@mednet.ucla.edu. ·Eur J Cancer · Pubmed #27596353.

ABSTRACT: BACKGROUND: In KEYNOTE-002, pembrolizumab significantly prolonged progression-free survival and was associated with a better safety profile compared with chemotherapy in patients with advanced melanoma that progressed after ipilimumab. We present health-related quality of life (HRQoL) outcomes from KEYNOTE-002. METHODS: Patients were randomly assigned 1:1:1 to pembrolizumab 2 or 10 mg/kg every 3 weeks (Q3W) or investigator-choice chemotherapy. HRQoL was assessed using the European Organisation for Research and Treatment of Cancer Quality-of-Life Questionnaire-Core 30 instrument. A constrained longitudinal data analysis model was implemented to assess between-arm differences in HRQoL scores. The study is registered with ClinicalTrials.gov, number NCT01704287. RESULTS: Of the 540 patients enrolled, 520 were included in the HRQoL analysis. Baseline global health status (GHS) was similar across treatment arms. Compliance rates at week 12 were 76.6% (n = 108), 82.3% (n = 121), and 86.4% (n = 133) for the control, pembrolizumab 2 mg/kg Q3W, and pembrolizumab 10 mg/kg Q3W arms, respectively. From baseline to week 12, GHS/HRQoL scores were maintained to a higher degree in the pembrolizumab arms compared with the chemotherapy arm (decrease of -2.6 for each pembrolizumab arm versus -9.1 for chemotherapy; P = 0.01 for each pembrolizumab arm versus chemotherapy). Fewer patients treated with pembrolizumab experienced deterioration in GHS at week 12 (31.8% for pembrolizumab 2 mg/kg, 26.6% for 10 mg/kg, and 38.3% for chemotherapy), with similar trends observed for the individual functioning and symptoms scales. CONCLUSIONS: HRQoL was better maintained with pembrolizumab than with chemotherapy in KEYNOTE-002, supporting the use of pembrolizumab in patients with ipilimumab-refractory melanoma.

7 Clinical Trial Open-label, multicenter, single-arm phase II DeCOG-study of ipilimumab in pretreated patients with different subtypes of metastatic melanoma. 2015

Zimmer, Lisa / Eigentler, Thomas K / Kiecker, Felix / Simon, Jan / Utikal, Jochen / Mohr, Peter / Berking, Carola / Kämpgen, Eckhart / Dippel, Edgar / Stadler, Rudolf / Hauschild, Axel / Fluck, Michael / Terheyden, Patrick / Rompel, Rainer / Loquai, Carmen / Assi, Zeinab / Garbe, Claus / Schadendorf, Dirk. ·Department of Dermatology, University Hospital, University Duisburg-Essen, Essen, Germany. lisa.zimmer@uk-essen.de. · Department of Dermatology, Center for Dermatooncology, University Medical Center Tübingen, Tübingen, Germany. thomas.eigentler@med.uni-tuebingen.de. · Department of Dermatology and Allergy, Skin Cancer Center, Charité-Universitätsmedizin Berlin, Berlin, Germany. felix.kiecker@charite.de. · Department of Dermatology, Venereology and Allergology, University Hospital Leipzig, Leipzig, Germany. Jan.simon@medizin.uni-leipzig.de. · Skin Cancer Unit, German Cancer Research Center (DKFZ), Heidelberg, Germany. jochen.utikal@umm.de. · Department of Dermatology, Venereology and Allergology, University Medical Center Mannheim, Ruprecht-Karl University of Heidelberg, Mannheim, Germany. jochen.utikal@umm.de. · Department of Dermatology, Elbekliniken Stade Buxtehude, Buxtehude, Germany. peter.mohr@elbekliniken.de. · Department of Dermatology and Allergy, Ludwig-Maximilian University, Munich, Germany. carola.berking@med.uni-muenchen.de. · Department of Dermatology, Dermatologikum Berlin, Berlin, Germany. Kaempgen@dermatologikum-berlin.de. · Department of Dermatology, Klinikum Ludwigshafen, Skin Cancer Center Rheinpfalz, Ludwigshafen, Germany. dippele@klilu.de. · Department of Dermatology, Medical Centre Minden, Minden, Germany. rudolf.stadler@muehlenkreiskliniken.de. · University Department of Dermatology, Kiel, Germany. ahauschild@dermatology.uni-kiel.de. · Department of Dermatology Hornheide, Münster, Germany. michael.fluck@fachklinik-hornheide.de. · Department of Dermatology, University of Lübeck, Lübeck, Germany. patrick.terheyden@uksh.de. · Department of Dermatology, Clinical Centre Kassel, Kassel, Germany. rompel@klinikum-kassel.de. · Department of Dermatology, University Medical Center, Johannes Gutenberg-University, Mainz, Germany. Carmen.Loquai@unimedizin-mainz.de. · Department of Dermatology, Center for Dermatooncology, University Medical Center Tübingen, Tübingen, Germany. zeinab.jradi.assi@gmail.com. · Department of Dermatology, Center for Dermatooncology, University Medical Center Tübingen, Tübingen, Germany. claus.garbe@uni-tuebingen.de. · Department of Dermatology, University Hospital, University Duisburg-Essen, Essen, Germany. dirk.schadendorf@uk-essen.de. ·J Transl Med · Pubmed #26541511.

ABSTRACT: BACKGROUND: Ipilimumab 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 METHODS: We 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. RESULTS: 103 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. CONCLUSIONS: Ipilimumab 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.

8 Clinical Trial Intermittent High-Dose Intravenous Interferon Alfa-2b for Adjuvant Treatment of Stage III Melanoma: Final Analysis of a Randomized Phase III Dermatologic Cooperative Oncology Group Trial. 2015

Mohr, Peter / Hauschild, Axel / Trefzer, Uwe / Enk, Alexander / Tilgen, Wolfgang / Loquai, Carmen / Gogas, Helen / Haalck, Thomas / Koller, Josef / Dummer, Reinhard / Gutzmer, Ralf / Brockmeyer, Norbert / Hölzle, Erhard / Sunderkötter, Cord / Mauch, Cornelia / Stein, Annette / Schneider, Lars A / Podda, Maurizio / Göppner, Daniela / Schadendorf, Dirk / Weichenthal, Michael. ·Peter Mohr, Elbe-Klinikum Buxtehude, Buxtehude · Axel Hauschild and Michael Weichenthal, University Hospital Schleswig-Holstein, Kiel · Uwe Trefzer, Charité-Universitätsmedizin Berlin, Berlin · Alexander Enk, University Hospital Heidelberg, Heidelberg · Wolfgang Tilgen, University Hospital, Homburg/Saarland · Carmen Loquai, University of Mainz, Mainz · Thomas Haalck, Universitätsklinikum Hamburg-Eppendorf, Hamburg · Ralf Gutzmer, Hannover Medical School, Hannover · Norbert Brockmeyer, Ruhr-Universität Bochum, Bochum · Erhard Hölzle, Oldenburg Hospital, Oldenburg · Cord Sunderkötter, University of Münster, Münster · Cornelia Mauch, University of Cologne, Cologne · Annette Stein, Universitätsklinikum Carl Gustav Carus, Dresden · Lars A. Schneider, University of Ulm, Ulm · Maurizio Podda, Darmstadt Hospital, Darmstadt · Daniela G[uml]oppner, University Hospital Magdeburg, Magdeburg · Dirk Schadendorf, University Hospital Essen, Essen, Germany · Helen Gogas, Hellenic Cooperative Oncology Group, Athens, Greece · Josef Koller, Paracelsus Medical University, Salzburg, Austria · and Reinhard Dummer, University Hospital of Zurich, Zurich, Switzerland. ·J Clin Oncol · Pubmed #26503196.

ABSTRACT: PURPOSE: To evaluate the efficacy, safety, tolerability, and quality of life (QoL) in patients receiving intravenous, intermittent high-dose interferon alfa-2b (IFN-α-2b [iHDI]) compared with standard high-dose IFN-α-2b (HDI). PATIENT AND METHODS: Patients with stage III resected lymph node or in-transit metastasis from cutaneous malignant melanoma were randomly assigned to receive either a standard HDI regimen or three courses of IFN-α-2b 20 MIU/m(2) administered intravenously 5 days a week for 4 weeks then repeated every 4 months. Distant metastasis-free survival was the primary end point for efficacy analysis. In addition, relapse-free survival, overall survival, safety as determined by Common Terminology Criteria for Adverse Events criteria, and QoL were secondary end points. RESULTS: Of 649 patients enrolled, 22 patients were excluded from the intent-to-treat analysis. The remaining 627 patients were well balanced between the arms according to sex, age, and stage. After a median follow-up of 55 months, a multivariable Cox model revealed no significant differences for distant metastasis-free survival (hazard ratio [HR], 1.21; P = .12) or overall survival (HR, 1.01; P = .85). In contrast, the difference for relapse-free survival was significant (HR, 1.27; P = .03), favoring standard HDI. Early termination of treatment because of adverse events or QoL occurred significantly more often with HDI than with iHDI (26.0% v 14.8%; P < .001). CONCLUSION: Although the safety and QoL profiles for the intermittent regimen were favorable, no significant difference was observed for survival while the HR for relapse with iHDI was increased. Therefore, an iHDI regimen, as tested here, cannot be recommended as adjuvant treatment for high-risk melanoma.

9 Clinical Trial A randomized, controlled phase III trial of nab-Paclitaxel versus dacarbazine in chemotherapy-naïve patients with metastatic melanoma. 2015

Hersh, E M / Del Vecchio, M / Brown, M P / Kefford, R / Loquai, C / Testori, A / Bhatia, S / Gutzmer, R / Conry, R / Haydon, A / Robert, C / Ernst, S / Homsi, J / Grob, J J / Kendra, K / Agarwala, S S / Li, M / Clawson, A / Brachmann, C / Karnoub, M / Elias, I / Renschler, M F / Hauschild, A. ·Department of Medicine, Arizona Cancer Center, Tucson, USA ehersh@azcc.arizona.edu. · Department of Medical Oncology, Fondazione IRCCS National Tumor Institute, Milan, Italy. · Cancer Clinical Trials Unit, Royal Adelaide Hospital and School of Medicine, University of Adelaide, Adelaide. · Sydney West Cancer Trials Centre/Westmead Hospital and Melanoma Institute Australia, University of Sydney, North Sydney, Australia. · Department of Dermatology, University of Mainz, Mainz, Germany. · Melanoma and Muscle Cutaneous Sarcoma Division, European Institute of Oncology, Milan, Italy. · Department of Medicine, Seattle Cancer Care Alliance, Seattle, USA. · Department of Dermatology and Oncology, Hannover Medical School, Hannover, Germany. · Division of Hematology and Oncology, University of Alabama at Birmingham, Birmingham, USA. · Department of Medical Oncology, Alfred Hospital, Melbourne, Australia. · Demartology Unit, Department of Medicine, The Gustave Roussy Cancer Institute, Villejuif, France. · Department of Medical Oncology, London Health Sciences Center-London Regional Cancer Program, London, Canada. · Department of Medical Oncology, Banner MD Anderson Cancer Center, Gilbert, USA. · Department of Dermatology, Timone Hospital, APHM and Aix-Marseille University, Marseille, France. · Department of Internal Medicine, Division of Medical Oncology, Ohio State University Comprehensive Cancer Center, Columbus. · Department of Hematology and Oncology, St Luke's Cancer Center and Temple University, Bethlehem. · Biometrics and Data Operations/Translational Medicine/Biometrics and Data Operations/Clinical Research & Development/Global Medical Affairs, Celgene Corporation, Summit, USA. · Department of Dermatology, University Medical Center Schleswig-Holstein, Kiel, Germany. ·Ann Oncol · Pubmed #26410620.

ABSTRACT: BACKGROUND: The efficacy and safety of nab-paclitaxel versus dacarbazine in patients with metastatic melanoma was evaluated in a phase III randomized, controlled trial. PATIENTS AND METHODS: Chemotherapy-naïve patients with stage IV melanoma received nab-paclitaxel 150 mg/m(2) on days 1, 8, and 15 every 4 weeks or dacarbazine 1000 mg/m(2) every 3 weeks. The primary end point was progression-free survival (PFS) by independent radiologic review; the secondary end point was overall survival (OS). RESULTS: A total of 529 patients were randomized to nab-paclitaxel (n = 264) or dacarbazine (n = 265). Baseline characteristics were well balanced. The majority of patients were men (66%), had an Eastern Cooperative Oncology Group status of 0 (71%), and had M1c stage disease (65%). The median PFS (primary end point) was 4.8 months with nab-paclitaxel and 2.5 months with dacarbazine [hazard ratio (HR), 0.792; 95.1% confidence interval (CI) 0.631-0.992; P = 0.044]. The median OS was 12.6 months with nab-paclitaxel and 10.5 months with dacarbazine (HR, 0.897; 95.1% CI 0.738-1.089; P = 0.271). Independently assessed overall response rate was 15% versus 11% (P = 0.239), and disease control rate (DCR) was 39% versus 27% (P = 0.004) for nab-paclitaxel versus dacarbazine, respectively. The most common grade ≥3 treatment-related adverse events were neuropathy (nab-paclitaxel, 25% versus dacarbazine, 0%; P < 0.001), and neutropenia (nab-paclitaxel, 20% versus dacarbazine, 10%; P = 0.004). There was no correlation between secreted protein acidic and rich in cysteine (SPARC) status and PFS in either treatment arm. CONCLUSIONS: nab-Paclitaxel significantly improved PFS and DCR compared with dacarbazine, with a manageable safety profile.

10 Clinical Trial Pembrolizumab versus investigator-choice chemotherapy for ipilimumab-refractory melanoma (KEYNOTE-002): a randomised, controlled, phase 2 trial. 2015

Ribas, Antoni / Puzanov, Igor / Dummer, Reinhard / Schadendorf, Dirk / Hamid, Omid / Robert, Caroline / Hodi, F Stephen / Schachter, Jacob / Pavlick, Anna C / Lewis, Karl D / Cranmer, Lee D / Blank, Christian U / O'Day, Steven J / Ascierto, Paolo A / Salama, April K S / Margolin, Kim A / Loquai, Carmen / Eigentler, Thomas K / Gangadhar, Tara C / Carlino, Matteo S / Agarwala, Sanjiv S / Moschos, Stergios J / Sosman, Jeffrey A / Goldinger, Simone M / Shapira-Frommer, Ronnie / Gonzalez, Rene / Kirkwood, John M / Wolchok, Jedd D / Eggermont, Alexander / Li, Xiaoyun Nicole / Zhou, Wei / Zernhelt, Adriane M / Lis, Joy / Ebbinghaus, Scot / Kang, S Peter / Daud, Adil. ·University of California, Los Angeles, Los Angeles, CA, USA. Electronic address: aribas@mednet.ucla.edu. · Vanderbilt-Ingram Cancer Center, Nashville, TN, USA. · University of Zürich, Zürich, Switzerland. · University Hospital Essen, Essen, Germany. · The Angeles Clinic and Research Institute, Los Angeles, CA, USA. · Gustave Roussy and Paris-Sud University, Villejuif, France. · Dana-Farber Cancer Institute, Boston, MA, USA. · Sheba Medical Center, Tel Hashomer, Israel. · New York University Cancer Institute, New York, NY, USA. · University of Colorado Denver, Aurora, CO, USA. · University of Arizona Cancer Center, Tucson, AZ, USA. · Netherlands Cancer Institute, Amsterdam, Netherlands. · Beverly Hills Cancer Center, Beverly Hills, CA, USA. · Istituto Nazionale Tumori Fondazione G. Pascale, Napoli, Italy. · Duke Cancer Institute, Durham, NC, USA. · Seattle Cancer Care Alliance/University of Washington, Seattle, WA, USA. · University Medical Center, Mainz, Germany. · Universitätsklinikum Tübingen, Tübingen, Germany. · Abramson Cancer Center of the University of Pennsylvania, Philadelphia, PA, USA. · Crown Princess Mary Cancer Centre, Westmead and Blacktown Hospitals, and Melanoma Institute Australia, Westmead, NSW, Australia. · St Luke's Cancer Center, Bethlehem, PA, USA; Temple University, Philadelphia, PA, USA. · University of North Carolina, Chapel Hill, NC, USA. · University of Pittsburgh, Pittsburgh, PA, USA. · Memorial Sloan Kettering Cancer Center, New York, NY, USA. · Merck & Co, Kenilworth, NJ, USA. · University of California, San Francisco, San Francisco, CA, USA. ·Lancet Oncol · Pubmed #26115796.

ABSTRACT: BACKGROUND: Patients with melanoma that progresses on ipilimumab and, if BRAF(V600) mutant-positive, a BRAF or MEK inhibitor or both, have few treatment options. We assessed the efficacy and safety of two pembrolizumab doses versus investigator-choice chemotherapy in patients with ipilimumab-refractory melanoma. METHODS: We carried out a randomised phase 2 trial of patients aged 18 years or older from 73 hospitals, clinics, and academic medical centres in 12 countries who had confirmed progressive disease within 24 weeks after two or more ipilimumab doses and, if BRAF(V600) mutant-positive, previous treatment with a BRAF or MEK inhibitor or both. Patients had to have resolution of all ipilimumab-related adverse events to grade 0-1 and prednisone 10 mg/day or less for at least 2 weeks, an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1, and at least one measurable lesion to be eligible. Using a centralised interactive voice response system, we randomly assigned (1:1:1) patients in a block size of six to receive intravenous pembrolizumab 2 mg/kg or 10 mg/kg every 3 weeks or investigator-choice chemotherapy (paclitaxel plus carboplatin, paclitaxel, carboplatin, dacarbazine, or oral temozolomide). Randomisation was stratified by ECOG performance status, lactate dehydrogenase concentration, and BRAF(V600) mutation status. Individual treatment assignment between pembrolizumab and chemotherapy was open label, but investigators and patients were masked to assignment of the dose of pembrolizumab. We present the primary endpoint at the prespecified second interim analysis of progression-free survival in the intention-to-treat population. This study is registered with ClinicalTrials.gov, number NCT01704287. The study is closed to enrolment but continues to follow up and treat patients. FINDINGS: Between Nov 30, 2012, and Nov 13, 2013, we enrolled 540 patients: 180 patients were randomly assigned to receive pembrolizumab 2 mg/kg, 181 to receive pembrolizumab 10 mg/kg, and 179 to receive chemotherapy. Based on 410 progression-free survival events, progression-free survival was improved in patients assigned to pembrolizumab 2 mg/kg (HR 0·57, 95% CI 0·45-0·73; p<0·0001) and those assigned to pembrolizumab 10 mg/kg (0·50, 0·39-0·64; p<0·0001) compared with those assigned to chemotherapy. 6-month progression-free survival was 34% (95% CI 27-41) in the pembrolizumab 2 mg/kg group, 38% (31-45) in the 10 mg/kg group, and 16% (10-22) in the chemotherapy group. Treatment-related grade 3-4 adverse events occurred in 20 (11%) patients in the pembrolizumab 2 mg/kg group, 25 (14%) in the pembrolizumab 10 mg/kg group, and 45 (26%) in the chemotherapy group. The most common treatment-related grade 3-4 adverse event in the pembrolizumab groups was fatigue (two [1%] of 178 patients in the 2 mg/kg group and one [<1%] of 179 patients in the 10 mg/kg group, compared with eight [5%] of 171 in the chemotherapy group). Other treatment-related grade 3-4 adverse events include generalised oedema and myalgia (each in two [1%] patients) in those given pembrolizumab 2 mg/kg; hypopituitarism, colitis, diarrhoea, decreased appetite, hyponatremia, and pneumonitis (each in two [1%]) in those given pembrolizumab 10 mg/kg; and anaemia (nine [5%]), fatigue (eight [5%]), neutropenia (six [4%]), and leucopenia (six [4%]) in those assigned to chemotherapy. INTERPRETATION: These findings establish pembrolizumab as a new standard of care for the treatment of ipilimumab-refractory melanoma. FUNDING: Merck Sharp & Dohme.

11 Clinical Trial A randomised, phase II study of intetumumab, an anti-αv-integrin mAb, alone and with dacarbazine in stage IV melanoma. 2011

O'Day, S / Pavlick, A / Loquai, C / Lawson, D / Gutzmer, R / Richards, J / Schadendorf, D / Thompson, J A / Gonzalez, R / Trefzer, U / Mohr, P / Ottensmeier, C / Chao, D / Zhong, B / de Boer, C J / Uhlar, C / Marshall, D / Gore, M E / Lang, Z / Hait, W / Ho, P / Anonymous1060700. ·The Angeles Clinic and Research Institute, 2001 Santa Monica Boulevard, Suite 560W, Santa Monica, CA, USA. soday@theangelesclinic.org ·Br J Cancer · Pubmed #21750555.

ABSTRACT: BACKGROUND: α(v) integrins are involved in angiogenesis and melanoma tumourigenesis. Intetumumab (CNTO 95) is a fully human anti-α(v)-integrin monoclonal antibody. METHODS: In a multicentre, randomised, phase II study, stage IV melanoma patients were randomised 1:1:1:1 to 1000 mg m(-2) dacarbazine+placebo (n=32), 1000 mg m(-2) dacarbazine+10 mg kg(-1) intetumumab (n=32), 10 mg kg(-1) intetumumab (n=33), or 5 mg kg(-1) intetumumab (n=32) q3w. The primary endpoint was progression-free survival (PFS). Secondary endpoints included overall survival (OS), objective response rate (ORR), adverse events, and pharmacokinetics. RESULTS: No statistically significant differences in efficacy were observed between groups. In the dacarbazine+placebo, dacarbazine+intetumumab, 10 mg kg(-1) intetumumab, and 5 mg kg(-1) intetumumab groups, median PFS was 1.8, 2.5, 1.4, and 1.4 months; median OS was 8, 11, 15, and 9.8 months; and ORR of complete+partial response was 10, 3, 6, and 0%. Nonlinear intetumumab pharmacokinetics and potential intetumumab-dacarbazine interactions were observed. Transient, asymptomatic, nonrecurring, grade 1-2, uveitic reactions that resolved spontaneously or with topical steroids were seen in 22-30% of intetumumab-treated patients. Low-grade infusion-reaction symptoms (headache, fatigue, nausea, vomiting, fever, chills) were observed, as expected, in 16-73% of dacarbazine-treated patients. No intetumumab-related myelosuppression, laboratory/electrocardiogram abnormalities, or deaths occurred. CONCLUSION: With its favourable safety profile and a nonsignificant trend towards improved OS, intetumumab merits further investigation in advanced melanoma.

12 Article Long-term survival of patients after ipilimumab and hypofractionated brain radiotherapy for brain metastases of malignant melanoma: sequence matters. 2018

Schmidberger, Heinz / Rapp, Matthias / Ebersberger, Anne / Hey-Koch, Silla / Loquai, Carmen / Grabbe, Stephan / Mayer, Arnulf. ·Department of Radiation Oncology, University Medical Center of the Johannes Gutenberg University, Langenbeckstr. 1, 55131, Mainz, Germany. · Department of Dermatology, University Medical Center of the Johannes Gutenberg University, Mainz, Germany. · Department of Radiation Oncology, University Medical Center of the Johannes Gutenberg University, Langenbeckstr. 1, 55131, Mainz, Germany. arnmayer@uni-mainz.de. ·Strahlenther Onkol · Pubmed #30298365.

ABSTRACT: PURPOSE: Since the introduction of ipilimumab (IPI) for the treatment of patients with metastatic malignant melanoma, we have observed remarkable responses after hypofractionated whole brain irradiation (WBRT) or stereotactic radiotherapy (STX) for brain metastases of malignant melanoma. We sought to investigate the impact of the sequence of these treatment modalities. METHODS: We retrospectively evaluated the survival of melanoma patients with brain metastases who were treated with WBRT or STX and received IPI in close temporal relation between October 2010 and March 2015. Follow-up was obtained until November 2016. A total of 27 patients with advanced melanoma and brain metastases who were treated with WBRT before 2010, and who had not received IPI, served as historical controls. RESULTS: We identified a total of 41 patients of whom 15 were treated with STX, 7 with a combination of STX and WBRT and 19 with WBRT alone. All patients received at least 2 doses of IPI. The median time interval between radiotherapy and IPI was 2 months. Patients treated with IPI after radiotherapy had a censored median survival of 11 months, compared with 3 months for the patients who received IPI prior to radiotherapy. Patients who received IPI before radiotherapy showed a similar survival as historical controls, who had not received IPI. We observed long-term survivors after radiotherapy of brain metastases followed by IPI. CONCLUSIONS: These data suggest that the sequence of RT and immune checkpoint inhibition with IPI may be crucial for the success of combined modality treatment of melanoma brain metastases.

13 Article Fear of cancer progression in patients with stage IA malignant melanoma. 2018

Wagner, Tobias / Augustin, Matthias / Blome, Christine / Forschner, Andrea / Garbe, Claus / Gutzmer, Ralf / Hauschild, Axel / Heinzerling, Lucie / Livingstone, Elisabeth / Loquai, Carmen / Schadendorf, Dirk / Terheyden, Patrick / Mueller-Brenne, Tina / Kähler, Katharina C. ·German Center for Health Services Research in Dermatology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany. · Department of Dermatology, Eberhard-Karls University of Tuebingen, Tuebingen, Germany. · Skin Cancer Center Hannover, Hannover Medical School, Hannover, Germany. · Department of Dermatology, Skin Cancer Center, University of Kiel, Kiel, Germany. · Department of Dermatology, University Hospital Erlangen, Erlangen, Germany. · Department of Dermatology, University Hospital Essen, Essen, Germany. · Department of Dermatology, University Medical Center Mainz, Mainz, Germany. · Department of Dermatology, University Hospital (UKSH), Luebeck, Germany. ·Eur J Cancer Care (Engl) · Pubmed #30126009.

ABSTRACT: We aimed to determine the prevalence and importance of fear of cancer progression (FoP) in melanoma patients with stage IA tumours to assess psychosocial and demographic factors associated with severity of FoP and to determine the relationship of FoP and quality of life (QoL). One hundred and thirty-six patients with stage IA melanoma completed the short version of the Fear of Progression Questionnaire (FoP-Q-SF), the Hospital Anxiety and Depression Scale (HADS) and the EORTC-QLQ-C30. We found a mean FoP-Q-SF sum score of 30.2 points (±8.4 points SD). In this study, 33% of patients reported high FoP at or above the cutoff-value of 34 points. Higher FoP was found in women (p < 0.01), young (p = 0.03) and employed (p = 0.02) patients. Being confronted with a cancer diagnosis in closely related persons predicted higher FoP (p < 0.01). FoP correlated positively with the HADS anxiety (r = 0.50, p < 0.01) and depression scales (r = 0.26, p < 0.01) and negatively with the EORTC-QLQ-C30 global health state (r = -0.32, p < 0.01). FoP is considerably prevalent in low-risk melanoma patients and associated with reduced QoL, cancer in related persons, women sex and participation in working life. Considerably high levels of FoP, even in patients with low-risk malignancies, underline the need for psychosocial support and psychotherapeutic interventions for melanoma patients.

14 Article Willingness to pay for a cure of low-risk melanoma patients in Germany. 2018

Augustin, Matthias / Blome, Christine / Forschner, Andrea / Gutzmer, Ralf / Hauschild, Axel / Heinzerling, Lucie / Livingstone, Elisabeth / Loquai, Carmen / Schadendorf, Dirk / Utikal, Jochen / Wagner, Tobias / Wilden, Sophia / Kähler, Katharina C. ·Institute for Health Services Research in Dermatology and Nursing (IVDP), University Medical Center Hamburg, Germany. · Department of Dermatology, Eberhard-Karls University of Tübingen, Tübingen, Germany. · Skin Cancer Center Hannover, Department of Dermatology, Hannover Medical School, Hannover, Germany. · Skin Cancer Center, Department of Dermatology, University Hospital Schleswig-Holstein (UKSH), Campus Kiel, Kiel, Germany. · Department of Dermatology, University Hospital Erlangen, Erlangen, Germany. · Department of Dermatology, University Hospital Essen, University Duisburg-Essen, Essen, Germany. · Department of Dermatology, University of Mainz, Mainz, Germany. · Skin Cancer Unit, German Cancer Research Center (DKFZ), Heidelberg, Germany. · Department of Dermatology, Venereology and Allergology, University Medical Center Mannheim, Mannheim, Germany. ·PLoS One · Pubmed #29795621.

ABSTRACT: Malignant melanoma is potentially life-threatening but in most cases curable if detected early. Willingness to pay (WTP) is a preference-based construct that reflects burden of disease by assessment of the monetary value for a hypothetical cure from disease. Since WTP (directly as total amount of money) has not been assessed so far in patients with low risk melanoma, it was interesting to gain insights in this patient population and then, in a second step, compare it directly with the WTP of their treating dermato-oncologists. WTP was assessed in 125 patients with low-risk melanoma and additionally in 105 treating physicians, asking for the one-time and continuous payments they would be willing to make for a sustainable cure, both as absolute sums and as percentages of monthly income. The median WTP based on one-time payment was €10,000 for patients and €100,000 for physicians; relative numbers were 100% versus 300% of monthly income. For continuous monthly payments, WTP was €500 for patients and €1000 for physicians, relative numbers 25% and 50% of income, respectively. Even after controlling for income differences, there was a significantly higher WTP in physicians for all four questions. Compared to patients with chronic skin diseases such as vitiligo, rosacea, atopic eczema and psoriasis, patients with low-risk melanoma showed a significantly higher WTP. Our data suggest that there is a relevant burden of disease even in patients with low-risk tumors. Higher WTP of physicians underlines the prevalence of differences in disease perception.

15 Article Ipilimumab in metastatic melanoma patients with pre-existing autoimmune disorders. 2018

Kähler, Katharina C / Eigentler, Thomas K / Gesierich, Anja / Heinzerling, Lucie / Loquai, Carmen / Meier, Friedegund / Meiss, Frank / Pföhler, Claudia / Schlaak, Max / Terheyden, Patrick / Thoms, Kai M / Ziemer, Mirjana / Zimmer, Lisa / Gutzmer, Ralf / Anonymous4140938. ·Department of Dermatology, Campus Kiel, University Hospital Schleswig-Holstein (UKSH), Rosalind-Franklind-Str. 7, 24105, Kiel, Germany. kkaehler@dermatology.uni-kiel.de. · Department of Dermatology, Eberhard-Karls University of Tübingen, Tübingen, Germany. · Department of Dermatology, University Hospital Würzburg, Würzburg, Germany. · Department of Dermatology, University Hospital Erlangen, Erlangen, Germany. · Department of Dermatology, University Medical Center of Mainz, Mainz, Germany. · Department of Dermatology, University of Dresden, Dresden, Germany. · Department of Dermatology, Medical Center - Faculty of Medicine, University of Freiburg, Freiburg, Germany. · Department of Dermatology, Saarland University Medical School, Homburg/saar, Germany. · Department of Dermatology, Skin Cancer Center at Center of Integrated Oncology (CIO), University Hospital Cologne, Cologne-Bonn, Germany. · Department of Dermatology, Campus LübeckUniversity, Hospital (UKSH), Lübeck, Germany. · Department of Dermatology, University Medical Center Göttingen, Göttingen, Germany. · Department of Dermatology, University Hospital Leipzig, Leipzig, Germany. · Department of Dermatology, Essen, Germany and German Cancer Consortium (DKTK), University Duisburg-Essen, University Hospital Essen, Heidelberg, Germany. · Department of Dermatology and Allergy, Skin Cancer Center Hannover, Hannover Medical School, Hanover, Germany. ·Cancer Immunol Immunother · Pubmed #29487980.

ABSTRACT: BACKGROUND: Ipilimumab and programmed death (PD) 1-antibodies are effective treatment options in metastatic melanoma. The safety and efficacy of ipilimumab in patients with pre-existing autoimmune disorders (AD) has only been evaluated in a selected number of patients. METHODS: We performed a retrospective analysis in 14 German skin cancer centers for patients with metastatic melanoma and pre-existing AD treated with ipilimumab. RESULTS: 41 patients with 44 pre-existing AD were treated with ipilimumab (thyroiditis n = 15, rheumatoid n = 11, dermatologic n = 10, Crohn's disease/ulcerative colitis n = 3, neurological n = 2, sarcoidosis n = 2, pancreatitis n = 1). 3 out of 41 patients had two AD, 11 patients required immunosuppressants at the time of induction of ipilimumab. 12 patients (29.2%) experienced a flare of their pre-existing AD, mainly patients with rheumatoid or dermatologic diseases. Additional immune-related adverse events (irAEs) occurred in 12 patients (29.2%). In 23 patients (56%) neither a change of their AD nor additional irAEs were observed. Objective responses were seen in five patients (one complete remission, four partial remissions, 12.1%). CONCLUSION: This is the largest series of patients with pre-existing AD and treatment with ipilimumab reported. Flares of pre-existing AD were observed but manageable. Response rates and occurrence of new irAEs were comparable to previous trials. Thus, in this patient subgroup, ipilimumab can be a treatment option after a thorough discussion of pros and cons and taking severity and activity of the preexisting AD into account.

16 Article Clinical outcome of concomitant vs interrupted BRAF inhibitor therapy during radiotherapy in melanoma patients. 2018

Hecht, Markus / Meier, Friedegund / Zimmer, Lisa / Polat, Bülent / Loquai, Carmen / Weishaupt, Carsten / Forschner, Andrea / Gutzmer, Ralf / Utikal, Jochen S / Goldinger, Simone M / Geier, Michael / Hassel, Jessica C / Balermpas, Panagiotis / Kiecker, Felix / Rauschenberg, Ricarda / Dietrich, Ursula / Clemens, Patrick / Berking, Carola / Grabenbauer, Gerhard / Schadendorf, Dirk / Grabbe, Stephan / Schuler, Gerold / Fietkau, Rainer / Distel, Luitpold V / Heinzerling, Lucie. ·Department of Radiation Oncology, University Hospital Erlangen, Erlangen, Germany. · Department of Dermatology, University Hospital Dresden, Dresden, Germany. · Department of Dermatology, University Hospital Essen, Essen, Germany. · Department of Radiation Oncology, University Hospital Würzburg, Würzburg, Germany. · Department of Dermatology, University Medical Center Mainz, Mainz, Germany. · Department of Dermatology, University Hospital Münster, Münster, Germany. · Department of Dermatology, University Hospital Tübingen, Tübingen, Germany. · Skin Cancer Center Hannover, Department of Dermatology and Allergy, Hannover Medical School, Hannover, Germany. · 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. · Department of Dermatology, University Hospital Zürich, Zürich, Switzerland. · Department of Radiation Oncology, Ordensklinikum Linz, Linz, Austria. · Department of Dermatology, University Hospital Heidelberg, Heidelberg, Germany. · Department of Radiation Oncology, University Hospital Frankfurt, Frankfurt, Germany. · Department of Dermatology, University Hospital Berlin, Berlin, Germany. · Department of Radiation Oncology, Hospital Feldkirch, Feldkirch, Austria. · Department of Dermatology, University Hospital LMU Munich, München, Germany. · Department of Radiation Oncology, Hospital Coburg, Coburg, Germany. · Department of Dermatology, University Hospital Erlangen, Erlangen, Germany. ·Br J Cancer · Pubmed #29438368.

ABSTRACT: This corrects the article DOI: 10.1038/bjc.2017.85.

17 Article Long-term survival with modern therapeutic agents against metastatic melanoma-vemurafenib and ipilimumab in a daily life setting. 2018

Lang, B M / Peveling-Oberhag, A / Faidt, D / Hötker, A M / Weyer-Elberich, V / Grabbe, S / Loquai, C. ·Department of Dermatology, University Medical Center of the Johannes Gutenberg University Mainz, Langenbeckstr. 1, 55131, Mainz, Germany. berenice.lang@unimedizin-mainz.de. · Department of Dermatology, University Medical Center of the Johannes Gutenberg University Mainz, Langenbeckstr. 1, 55131, Mainz, Germany. · Department of Radiology, University Medical Center of the Johannes Gutenberg University Mainz, Langenbeckstr. 1, 55131, Mainz, Germany. · Institute for Medical Biostatistics, Epidemiology and Informatics, University Medical Center of the Johannes Gutenberg University Mainz, Langenbeckstr. 1, 55131, Mainz, Germany. ·Med Oncol · Pubmed #29387968.

ABSTRACT: Despite new therapeutic options, metastatic melanoma remains to be one of the most fatal tumors. With the development of BRAF inhibitors and immune checkpoint inhibitors, overall survival could be prolonged significantly for the first time. Clinical studies implied that even long-term survival is possible with both types of drugs, but predictive markers are so far missing. In this study, we analyzed survival data from patients that received the first-in-class substances vemurafenib and ipilimumab, respectively, during the time period from registration of the drugs until availability of combination treatments. We aimed to evaluate the possibility of long-term survival in a daily life setting and to characterize patients that benefit from these drugs in order to gain insight into predictive attributes. Eighty patients were evaluated who were treated with either vemurafenib (n = 40) or ipilimumab (n = 40), and overall survival was analyzed. Subgroup analysis was performed for patients who were still alive 24 months after induction of therapy (long-term survival). Median overall survival (OS) was 8.0 months for patients treated with vemurafenib and 10.0 months for patients treated with ipilimumab (log-rank P value = 0.689). Long-term survival was achieved in 32.5% of patients (42.3% vemurafenib, 57.7% ipilimumab). Negative predictors of long-term survival in the vemurafenib group were brain and liver metastases, as well as elevated LDH, S100ß and liver enzymes. For ipilimumab, an increase in lymphocytes and eosinophils during course of treatment correlated with long-term survival. Our real-life experience shows that long-term survival is possible with using both therapeutic agents, vemurafenib and ipilimumab. Pattern of metastases and laboratory values might be of interest in decision making for a specific therapeutic approach. Combination of drugs and observational studies in larger patient cohorts are necessary to further validate our findings.

18 Article Personalized RNA mutanome vaccines mobilize poly-specific therapeutic immunity against cancer. 2017

Sahin, Ugur / Derhovanessian, Evelyna / Miller, Matthias / Kloke, Björn-Philipp / Simon, Petra / Löwer, Martin / Bukur, Valesca / Tadmor, Arbel D / Luxemburger, Ulrich / Schrörs, Barbara / Omokoko, Tana / Vormehr, Mathias / Albrecht, Christian / Paruzynski, Anna / Kuhn, Andreas N / Buck, Janina / Heesch, Sandra / Schreeb, Katharina H / Müller, Felicitas / Ortseifer, Inga / Vogler, Isabel / Godehardt, Eva / Attig, Sebastian / Rae, Richard / Breitkreuz, Andrea / Tolliver, Claudia / Suchan, Martin / Martic, Goran / Hohberger, Alexander / Sorn, Patrick / Diekmann, Jan / Ciesla, Janko / Waksmann, Olga / Brück, Alexandra-Kemmer / Witt, Meike / Zillgen, Martina / Rothermel, Andree / Kasemann, Barbara / Langer, David / Bolte, Stefanie / Diken, Mustafa / Kreiter, Sebastian / Nemecek, Romina / Gebhardt, Christoffer / Grabbe, Stephan / Höller, Christoph / Utikal, Jochen / Huber, Christoph / Loquai, Carmen / Türeci, Özlem. ·Biopharmaceutical New Technologies (BioNTech) Corporation, An der Goldgrube 12, 55131 Mainz, Germany. · TRON - Translational Oncology at the University Medical Center of Johannes Gutenberg University gGmbH, Freiligrathstraße 12, 55131 Mainz, Germany. · University Medical Center of the Johannes Gutenberg University, Langenbeckstraße 1, 55131 Mainz, Germany. · EUFETS GmbH, Vollmersbachstraße 66, 55743 Idar-Oberstein, Germany. · Medical University of Vienna, Spitalgasse 23, 1090 Vienna, Austria. · German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany. · University Medical Center Mannheim, Heidelberg University, Theodor-Kutzer-Ufer 1-3, 68135 Mannheim, Germany. · CI3 - Cluster for Individualized Immunointervention e.V, Hölderlinstraße 8, 55131 Mainz, Germany. ·Nature · Pubmed #28678784.

ABSTRACT: T cells directed against mutant neo-epitopes drive cancer immunity. However, spontaneous immune recognition of mutations is inefficient. We recently introduced the concept of individualized mutanome vaccines and implemented an RNA-based poly-neo-epitope approach to mobilize immunity against a spectrum of cancer mutations. Here we report the first-in-human application of this concept in melanoma. We set up a process comprising comprehensive identification of individual mutations, computational prediction of neo-epitopes, and design and manufacturing of a vaccine unique for each patient. All patients developed T cell responses against multiple vaccine neo-epitopes at up to high single-digit percentages. Vaccine-induced T cell infiltration and neo-epitope-specific killing of autologous tumour cells were shown in post-vaccination resected metastases from two patients. The cumulative rate of metastatic events was highly significantly reduced after the start of vaccination, resulting in a sustained progression-free survival. Two of the five patients with metastatic disease experienced vaccine-related objective responses. One of these patients had a late relapse owing to outgrowth of β2-microglobulin-deficient melanoma cells as an acquired resistance mechanism. A third patient developed a complete response to vaccination in combination with PD-1 blockade therapy. Our study demonstrates that individual mutations can be exploited, thereby opening a path to personalized immunotherapy for patients with cancer.

19 Article Prognostic factors and outcomes in metastatic uveal melanoma treated with programmed cell death-1 or combined PD-1/cytotoxic T-lymphocyte antigen-4 inhibition. 2017

Heppt, Markus V / Heinzerling, Lucie / Kähler, Katharina C / Forschner, Andrea / Kirchberger, Michael C / Loquai, Carmen / Meissner, Markus / Meier, Friedegund / Terheyden, Patrick / Schell, Beatrice / Herbst, Rudolf / Göppner, Daniela / Kiecker, Felix / Rafei-Shamsabadi, David / Haferkamp, Sebastian / Huber, Margit A / Utikal, Jochen / Ziemer, Mirjana / Bumeder, Irmgard / Pfeiffer, Christiane / Schäd, Susanne G / Schmid-Tannwald, Christoph / Tietze, Julia K / Eigentler, Thomas K / Berking, Carola. ·Department of Dermatology and Allergy, University Hospital Munich (LMU), Frauenlobstr. 9-11, 80337 Munich, Germany. Electronic address: Markus.Heppt@med.uni-muenchen.de. · Department of Dermatology, University Hospital Erlangen, Friedrich-Alexander-University Erlangen-Nürnberg (FAU), Ulmenweg 18, 91054 Erlangen, Germany. Electronic address: Lucie.Heinzerling@uk-erlangen.de. · Department of Dermatology, University Hospital Schleswig-Holstein, Campus Kiel, Rosalind-Franklin-Str. 7, 24105 Kiel, Germany. Electronic address: kkaehler@dermatology.uni-kiel.de. · Department of Dermatology, Center for Dermatooncology, University Hospital Tübingen, Liebermeisterstr. 25, 72076 Tübingen, Germany. Electronic address: andrea.forschner@med.uni-tuebingen.de. · Department of Dermatology, University Hospital Erlangen, Friedrich-Alexander-University Erlangen-Nürnberg (FAU), Ulmenweg 18, 91054 Erlangen, Germany. Electronic address: Michael.Kirchberger@uk-erlangen.de. · Department of Dermatology, University Medical Center Mainz, Langenbeckstr. 1, 55131 Mainz, Germany. Electronic address: Carmen.Loquai@unimedizin-mainz.de. · Department of Dermatology, Venereology and Allergology, Goethe University, Theodor-Stern Kai 7, 60590 Frankfurt am Main, Germany. Electronic address: Markus.Meissner@kgu.de. · Department of Dermatology, Skin Cancer Center, National Center for Tumor Diseases, Medical Faculty and University Hospital Carl Gustav Carus, TU Dresden, Fetscherstr. 74, 01307 Dresden, Germany. Electronic address: Friedegund.Meier@uniklinikum-dresden.de. · Department of Dermatology, University of Lübeck, Ratzeburger Allee 160, 23538 Lübeck, Germany. Electronic address: Patrick.Terheyden@uksh.de. · Department of Dermatology, SRH Wald-Klinikum Gera GmbH, Str. des Friedens 122, 07548 Gera, Germany. Electronic address: Beatrice.Schell@wkg.srh.de. · HELIOS Skin Cancer Center Erfurt, HELIOS Clinic Erfurt, Nordhäuser Str. 74, 99089 Erfurt, Germany. Electronic address: rudolf.herbst@helios-kliniken.de. · Department of Dermatology and Allergology, Justus Liebig University, University Medical Center Gießen and Marburg, Gaffkystr. 14, 35392 Gießen, Germany. Electronic address: Daniela.Goeppner@med.ovgu.de. · Department of Dermatology and Allergy, Skin Cancer Center, Charité Universitätsmedizin, Charitéplatz 1, 10117 Berlin, Germany. Electronic address: felix.kiecker@charite.de. · Department of Dermatology, Medical Center - University of Freiburg, Hauptstr. 7, 79104 Freiburg, Germany. Electronic address: david.rafei-shamsabadi@uniklinik-freiburg.de. · Department of Dermatology, University Hospital Regensburg, Franz-Josef-Strauß-Allee 11, 93053 Regensburg, Germany. Electronic address: Sebastian.Haferkamp@klinik.uni-regensburg.de. · Department of Dermatology and Allergic Diseases, Ulm University, Albert-Einstein-Allee 23, 89081 Ulm, Germany. Electronic address: margit.huber@uniklinik-ulm.de. · Skin Cancer Unit, German Cancer Research Center (DKFZ) and Department of Dermatology, Venereology and Allergology, University Medical Center Mannheim, Ruprecht-Karl University of Heidelberg, Theodor-Kutzer-Ufer 1-3, 68167 Mannheim, Germany. Electronic address: Jochen.Utikal@umm.de. · Department of Dermatology, Venereology, and Allergology, University Hospital Leipzig, Philipp-Rosenthal-Str. 23, 04103 Leipzig, Germany. Electronic address: Mirjana.Ziemer@medizin.uni-leipzig.de. · Clinic of Internal Medicine, University Hospital Munich (LMU), Ziemssenstr. 1, 80336 Munich, Germany. Electronic address: praxis@onkologie-ebersberg.de. · Department of Dermatology, Klinikum Augsburg, Sauerbruchstr. 6, 86179 Augsburg, Germany. Electronic address: Christiane.Pfeiffer@klinikum-augsburg.de. · Department of Dermatology and Venereology, University Medical Center Rostock, Strempelstr.13, 18057 Rostock, Germany. Electronic address: susanne.schaed@uni-rostock.de. · Institute for Clinical Radiology, University Hospital Munich (LMU), Ziemssenstr. 1, 80336 Munich, Germany. Electronic address: Christoph.Schmid-Tannwald@med.uni-muenchen.de. · Department of Dermatology and Allergy, University Hospital Munich (LMU), Frauenlobstr. 9-11, 80337 Munich, Germany. Electronic address: Julia.Tietze@med.uni-muenchen.de. · Department of Dermatology, Center for Dermatooncology, University Hospital Tübingen, Liebermeisterstr. 25, 72076 Tübingen, Germany. Electronic address: thomas.eigentler@med.uni-tuebingen.de. · Department of Dermatology and Allergy, University Hospital Munich (LMU), Frauenlobstr. 9-11, 80337 Munich, Germany. Electronic address: Carola.Berking@med.uni-muenchen.de. ·Eur J Cancer · Pubmed #28648699.

ABSTRACT: BACKGROUND: Uveal melanoma (UM) is an ocular malignancy with high potential for metastatic spread. In contrast to cutaneous melanoma, immunotherapy has not yet shown convincing efficacy in patients with UM. Combined immune checkpoint blockade with checkpoint programmed cell death-1 (PD-1) and checkpoint cytotoxic T-lymphocyte antigen-4 (CTLA-4) inhibition has not been systematically assessed for UM to date. PATIENTS AND METHODS: Patients with metastatic UM treated with either PD-1 inhibitor monotherapy or combined PD-1 inhibitor and ipilimumab (an anti-CTLA-4 monoclonal antibody) were included from 20 German skin cancer centres. Records from 96 cases were analysed for treatment outcomes. Clinical and blood parameters associated with overall survival (OS) or treatment response were identified with multivariate Cox regression and binary logistic regression. RESULTS: Eighty-six patients were treated with PD-1 inhibitors only (n = 54 for pembrolizumab, n = 32 for nivolumab) with a centrally confirmed response rate of 4.7%. Median OS was 14 months for pembrolizumab-treated and 10 months for nivolumab-treated patients (p = 0.765). Fifteen patients were treated with combined immune checkpoint blockade with partial response observed in two cases. Median OS was not reached in this group. Multivariate Cox regression identified Eastern Cooperative Oncology Group (ECOG) performance status (p = 0.002), elevated serum levels of lactate dehydrogenase (LDH) (p = 0.002) and C-reactive protein (CRP) (p = 0.001), and a relative eosinophil count (REC) <1.5% (p = 0.002) as independent risk factors for poor survival. Patients with elevated CRP and LDH and a REC <1.5% were at highest risk for disease progression and death (p = 0.001). CONCLUSIONS: Blood markers predict survival in metastatic UM treated with immune checkpoint blockade. Normal serum levels of LDH and CRP and a high REC may help identify patients with better prognosis.

20 Article Prognostic factors and treatment outcomes in 444 patients with mucosal melanoma. 2017

Heppt, Markus V / Roesch, Alexander / Weide, Benjamin / Gutzmer, Ralf / Meier, Friedegund / Loquai, Carmen / Kähler, Katharina C / Gesierich, Anja / Meissner, Markus / von Bubnoff, Dagmar / Göppner, Daniela / Schlaak, Max / Pföhler, Claudia / Utikal, Jochen / Heinzerling, Lucie / Cosgarea, Ioana / Engel, Jutta / Eckel, Renate / Martens, Alexander / Mirlach, Laura / Satzger, Imke / Schubert-Fritschle, Gabriele / Tietze, Julia K / Berking, Carola. ·Department of Dermatology and Allergy, Munich University Hospital (LMU), Frauenlobstr. 9-11, 80337 Munich, Germany. Electronic address: Markus.Heppt@med.uni-muenchen.de. · Department of Dermatology, University Hospital Essen, Hufelandstr. 55, 45122 Essen, Germany; German Cancer Consortium (DKTK), Germany. Electronic address: alexander.roesch@uk-essen.de. · Department of Dermatology, Center for Dermatooncology, University Hospital Tübingen, Liebermeisterstr. 25, 72076 Tübingen, Germany. Electronic address: benjamin.weide@med.uni-tuebingen.de. · Department for Dermatology and Allergy, Skin Cancer Center Hannover (HTZH), Hannover Medical School, Carl-Neuberg-Str. 1, 30625 Hannover, Germany. Electronic address: Gutzmer.Ralf@mh-hannover.de. · Department of Dermatology, Skin Cancer Center, National Center for Tumor Diseases, Medical Faculty and University Hospital Carl Gustav Carus, TU Dresden, Fetscherstr. 74, 01307 Dresden, Germany. Electronic address: Friedegund.Meier@uniklinikum-dresden.de. · Department of Dermatology, University Medical Center Mainz, Langenbeckstr. 1, 55131 Mainz, Germany. Electronic address: Carmen.Loquai@unimedizin-mainz.de. · Department of Dermatology, University Hospital Schleswig-Holstein, Campus Kiel, Rosalind-Franklin-Str. 7, 24105 Kiel, Germany. Electronic address: kkaehler@dermatology.uni-kiel.de. · Department of Dermatology, University Hospital Würzburg, Josef-Schneider-Str. 2, 97080 Würzburg, Germany. Electronic address: Gesierich_A@ukw.de. · Department of Dermatology, Venereology and Allergology, Goethe University, Theodor-Stern Kai 7, 60590 Frankfurt am Main, Germany. Electronic address: Markus.Meissner@kgu.de. · Department of Dermatology, Medical Center - University of Freiburg, Hauptstr. 7, 79104 Freiburg, Germany. Electronic address: dagmar.bubnoff@uniklinik-freiburg.de. · Department of Dermatology and Allergology, Justus Liebig University, University Medical Center Gießen and Marburg, Gaffkystr. 14, 35392 Gießen, Germany. Electronic address: Daniela.Goeppner@derma.med.uni-giessen.de. · Department of Dermatology and Venereology, Skin Cancer Center at the Center of Integrated Oncology (CIO) Köln Bonn, University Hospital of Cologne, Kerpener Str. 62, 50937 Cologne, Germany. Electronic address: max.schlaak@uk-koeln.de. · Saarland University Medical School, Department of Dermatology, Kirrberger Str. 100, 66421 Homburg, Saar, Germany. Electronic address: Claudia.Pfoehler@uniklinikum-saarland.de. · Skin Cancer Unit, German Cancer Research Center (DKFZ) and Department of Dermatology, Venereology and Allergology, University Medical Center Mannheim, Ruprecht-Karl University of Heidelberg, Theodor-Kutzer-Ufer 1-3, 68167 Mannheim, Germany. Electronic address: Jochen.Utikal@umm.de. · Department of Dermatology, University Hospital Erlangen, Friedrich-Alexander-University Erlangen-Nürnberg (FAU), Ulmenweg 18, 91054 Erlangen, Germany. Electronic address: Lucie.Heinzerling@uk-erlangen.de. · Department of Dermatology, University Hospital Essen, Hufelandstr. 55, 45122 Essen, Germany; German Cancer Consortium (DKTK), Germany. Electronic address: ioana.cosgarea@uk-essen.de. · Munich Cancer Registry (MCR) of the Munich Tumor Centre (TZM), Department of Medical Information Processing, Biometry and Epidemiology (IBE), University Hospital of Munich, Ludwig-Maximilian-University (LMU), Marchioninistr. 15, 81337 Munich, Germany. Electronic address: engel@ibe.med.uni-muenchen.de. · Munich Cancer Registry (MCR) of the Munich Tumor Centre (TZM), Department of Medical Information Processing, Biometry and Epidemiology (IBE), University Hospital of Munich, Ludwig-Maximilian-University (LMU), Marchioninistr. 15, 81337 Munich, Germany. Electronic address: eckel@ibe.med.uni-muenchen.de. · Department of Dermatology, Center for Dermatooncology, University Hospital Tübingen, Liebermeisterstr. 25, 72076 Tübingen, Germany. Electronic address: alexander.martens@med.uni-tuebingen.de. · Department of Dermatology and Allergy, Munich University Hospital (LMU), Frauenlobstr. 9-11, 80337 Munich, Germany. Electronic address: Laura.Mirlach@med.uni-muenchen.de. · Department for Dermatology and Allergy, Skin Cancer Center Hannover (HTZH), Hannover Medical School, Carl-Neuberg-Str. 1, 30625 Hannover, Germany. Electronic address: Satzger.Imke@mh-hannover.de. · Munich Cancer Registry (MCR) of the Munich Tumor Centre (TZM), Department of Medical Information Processing, Biometry and Epidemiology (IBE), University Hospital of Munich, Ludwig-Maximilian-University (LMU), Marchioninistr. 15, 81337 Munich, Germany. Electronic address: Gabriele.Schubert-Fritschle@med.uni-muenchen.de. · Department of Dermatology and Allergy, Munich University Hospital (LMU), Frauenlobstr. 9-11, 80337 Munich, Germany. Electronic address: Julia.Tietze@med.uni-muenchen.de. · Department of Dermatology and Allergy, Munich University Hospital (LMU), Frauenlobstr. 9-11, 80337 Munich, Germany. Electronic address: Carola.Berking@med.uni-muenchen.de. ·Eur J Cancer · Pubmed #28600969.

ABSTRACT: BACKGROUND: Mucosal melanoma (MM) is a rare but diverse cancer entity. Prognostic factors are not well established for Caucasians with MM. PATIENTS AND METHODS: We analysed the disease course of 444 patients from 15 German skin cancer centres. Disease progression was determined with the cumulative incidence function. Survival times were estimated with the Kaplan-Meier method. Prognostic parameters were identified with multivariate Cox regression analysis. RESULTS: Common anatomic sites of primary tumours were head and neck (MMHN, 37.2%), female genital tract (MMFG, 30.4%) and anorectal region (MMAN, 21.8%). MMAN patients showed the highest vertical tumour thickness (p = 0.001), had a more advanced nodal status (p = 0.014) and a higher percentage of metastatic disease (p = 0.001) at diagnosis. Mutations of NRAS (13.8%), KIT (8.6%) and BRAF (6.4%) were evenly distributed across all tumour site groups. Local relapses were observed in 32.4% and most commonly occurred in the MMHN group (p = 0.016). Male gender (p = 0.047), advanced tumour stage (p = 0.001), nodal disease (p = 0.001) and incomplete resection status (p = 0.001) were independent risk factors for disease progression. Overall survival (OS) was highest in the MMFG group (p = 0.030) and in patients without ulceration (p = 0.004). Multivariate risk factors for OS were M stage at diagnosis (p = 0.002) and incomplete resection of the primary tumour (p = 0.001). CONCLUSION: In this large series of MM patients in a European population, anorectal MM was associated with the poorest prognosis.

21 Article Acquired IFNγ resistance impairs anti-tumor immunity and gives rise to T-cell-resistant melanoma lesions. 2017

Sucker, Antje / Zhao, Fang / Pieper, Natalia / Heeke, Christina / Maltaner, Raffaela / Stadtler, Nadine / Real, Birgit / Bielefeld, Nicola / Howe, Sebastian / Weide, Benjamin / Gutzmer, Ralf / Utikal, Jochen / Loquai, Carmen / Gogas, Helen / Klein-Hitpass, Ludger / Zeschnigk, Michael / Westendorf, Astrid M / Trilling, Mirko / Horn, Susanne / Schilling, Bastian / Schadendorf, Dirk / Griewank, Klaus G / Paschen, Annette. ·Department of Dermatology, University Hospital Essen, University Duisburg-Essen, 45122 Essen, Germany. · German Cancer Consortium (DKTK), partner site Essen/Düsseldorf, 45122 Essen, Germany. · Institute of Virology, University Hospital Essen, University Duisburg-Essen, 45122 Essen, Germany. · Division of Dermatooncology, Department of Dermatology, University Medical Center Tübingen, 72076 Tübingen, Germany. · Department of Dermatology and Allergy, Skin Cancer Center Hannover, Hannover Medical School, 30625 Hannover, Germany. · German Cancer Research Center (DKFZ), Skin Cancer Unit, Heidelberg and University Medical Center Mannheim, Department of Dermatology, Venereology and Allergology, Ruprecht-Karl University of Heidelberg, 68167 Mannheim, Germany. · Skin Cancer Center, Department of Dermatology, University of Mainz Medical Center, 55131 Mainz, Germany. · First Department of Medicine,National and Kapodistrian University of Athens, 11527 Athens, Greece. · Institute of Cell Biology, University Hospital Essen, University of Duisburg-Essen, 45122 Essen, Germany. · Institute of Human Genetics, University Hospital Essen, University Duisburg-Essen, West German Cancer Center and the German Cancer Consortium (DKTK), 45122 Essen, Germany. · Institute of Medical Microbiology, University Hospital Essen, University of Duisburg-Essen, 45122 Essen, Germany. · Department of Dermatology, Venereology and Allergology, University Hospital Würzburg, 97080 Würzburg, Germany. ·Nat Commun · Pubmed #28561041.

ABSTRACT: Melanoma treatment has been revolutionized by antibody-based immunotherapies. IFNγ secretion by CD8

22 Article Interactions from complementary and alternative medicine in patients with melanoma. 2017

Loquai, Carmen / Schmidtmann, Irene / Garzarolli, Marlene / Kaatz, Martin / Kähler, Katharina C / Kurschat, Peter / Meiss, Frank / Micke, Oliver / Muecke, Ralph / Muenstedt, Karsten / Nashan, Dorothee / Stein, Annette / Stoll, Christoph / Dechent, Dagmar / Huebner, Jutta. ·aDepartment of Dermatology bDepartment of Medical Biometrie, Epidemiology and Informatics, University Medical Center Mainz, Mainz cDepartment of Dermatology, University Medical Center Dresden, Dresden dDepartment of Dermatology, Wald Klinikum Gera, Gera eDepartment of Dermatology, University Medical Center Kiel, Kiel fDepartment of Dermatology, University Hospital Cologne, Cologne gDepartment of Dermatology, University Medical Center Freiburg, Freiburg hDepartment of Radio-Oncology, Franziskus Hospital Bielefeld, Bielefeld iDepartment of Radio-Oncology, Ruhr University Bochum, Bochum jDepartment of Gynecology and Obstetrics, Clinic Offenburg, Offenburg kDepartment of Dermatology, Klinikum Dortmund gGmbH, Dortmund lPractice of Dermatology, Dresden mClinic Herzoghoehe Bayreuth, Bayreuth nInstitute of Occupational Medicine, University Hospital, RWTH Aachen University, Aachen oDr. Senckenberg Chronomedical Insitute, J.W. Goethe University Frankfurt, Frankfurt, Germany. ·Melanoma Res · Pubmed #28252553.

ABSTRACT: Biological-based (BbCAM) methods from complementary and alternative medicine (CAM) may interact with cancer treatments, reduce efficacy, or enhance adverse effects. Although CAM usage has been evaluated well in other cancer entities, data on melanoma patients are still missing. The aim of this study was to determine CAM usage of melanoma patients using a standardized questionnaire to identify potential interactions with established and new systemic melanoma therapies. This multicenter study was carried out in seven German skin cancer centers. During routine care contact, CAM usage of former and current melanoma treatment was assessed in melanoma patients. The probability of interaction was classified into four categories ranging from 'interaction unlikely' (I), 'possible' (II), 'likely' (III), or 'no data' (IV). The questionnaire was filled out by 1157 patients, of whom 1089 were eligible for evaluation. CAM usage was reported by 41% of melanoma patients, of whom 63.1% took BbCAM such as vitamins, trace elements, supplements, or phytotherapeuticals. Of 335 patients with former or current therapy, 28.1% used BbCAM. The melanoma treatment included interferon, radiotherapy, chemotherapy, BRAF-inhibitor, or other tyrosine kinase inhibitors and ipilimumab. On the basis of our model of likelihood of interaction, we found that 23.9% of those on cancer therapy and 85.1% of those also using BbCAM were at some risk of interactions. The main limitation of our study is that no reliable and comprehensive database on clinical relevant interactions with CAM in oncology exists. Most patients receiving a melanoma-specific treatment and using BbCAM methods are at risk for interactions, which raises concerns on the safety and treatment efficacy of these patients. To protect melanoma patients from potential harm by the combination of their cancer treatment and CAM usage, patients should systematically be encouraged to report their CAM use, while oncologists should be trained on evidence of CAM, and patient guidance for saver CAM use.

23 Article Use of complementary and alternative medicine: A multicenter cross-sectional study in 1089 melanoma patients. 2017

Loquai, Carmen / Dechent, Dagmar / Garzarolli, Marlene / Kaatz, Martin / Kaehler, Katharina C / Kurschat, Peter / Meiss, Frank / Micke, Oliver / Muecke, Ralph / Muenstedt, Karsten / Stein, Annette / Nashan, Dorothée / Stoll, Christoph / Schmidtmann, Irene / Huebner, Jutta. ·Department of Dermatology, University Medical Center Mainz, Germany. Electronic address: carmen.loquai@unimedizin-mainz.de. · Institute of Occupational Medicine, University Hospital, RWTH Aachen University, Germany. · Department of Dermatology, University Medical Center Dresden, Germany. · Department of Dermatology, Wald Klinikum Gera, Germany. · Department of Dermatology, University Hospital Schleswig-Holstein, Campus Kiel, Germany. · Department of Dermatology, University of Cologne, Germany. · Department of Dermatology, Medical Center - University of Freiburg, Germany. · Department of Radio-Oncology, Franziskus Hospital Bielefeld, Germany. · Department of Radio-Oncology, Ruhr University Bochum, Germany. · Department of Gynecology and Obstetrics, Clinic Offenburg, Germany. · Practice of Dermatology, Dresden, Germany. · Department of Dermatology, Klinikum Dortmund gGmbH, Germany. · Clinic Herzoghoehe Bayreuth, Germany. · Institute for Medical Biostatistics, Epidemiology and Informatics, University Medical Center Mainz, Germany. · Dr. Senckenberg Chronomedical Institute, J.W. Goethe University, Germany. ·Eur J Cancer · Pubmed #27984769.

ABSTRACT: BACKGROUND: About half of patients with cancer use complementary and alternative medicine (CAM). So far, data on melanoma patients are missing. OBJECTIVE: The aim of our study was to evaluate the prevalence and predictors for the use of CAM in this patient group. METHODS: All patients with melanoma being attended at one of 7 skin cancer centres in Germany between March 2012 and March 2013 were invited to take part in a survey using a structured questionnaire on CAM. The physicians filled in a second part on the diagnosis, state and former and current therapy. RESULTS: Nearly half of the 1089 participants (41.0%) used CAM and half of those using CAM (56.8%) marked that this made them feel better. Biological-based CAMs which consists of substances taken were used by 25.9% of all patients (63.1% of those using CAM). Predictors of CAM use were education, psychological support, interest in CAM and previous CAM use. CAM users show higher physical activity, more often use psychosocial help and have contact with a self-help group. Family and friends (41.0%) as well as print media (41.7%) are the main sources of information. Most important reasons to use CAM are to strengthen one's own forces (57.7%) or the immune system (63.4%) and to be able to do something for oneself (53.7%). CONCLUSION: Communication on CAM should become a regular topic in counselling melanoma patients. To increase safety, patients and physicians must have access to evidence-based information on these methods and their interactions with modern cancer treatments.

24 Article New-onset third-degree atrioventricular block because of autoimmune-induced myositis under treatment with anti-programmed cell death-1 (nivolumab) for metastatic melanoma. 2017

Behling, Juliane / Kaes, Joachim / Münzel, Thomas / Grabbe, Stephan / Loquai, Carmen. ·Departments of aDermatology bCardiology, University Hospital Mainz, Johannes Gutenberg - Universität Mainz, Mainz, Germany. ·Melanoma Res · Pubmed #27977496.

ABSTRACT: There has been considerable progress in treating malignant melanoma over the last few years. The immune-checkpoint-inhibitors nivolumab and pembrolizumab have been approved by the Food and Drug Administration in 2014 for the therapy of metastatic melanoma. Anti-programmed cell death-1-blocking antibodies are known to cause immune-related adverse events. Physicians should be aware of common and rare side effects and pay attention to new ones. We therefore report a severe and life-threatening side effect of anti-programmed cell death-1 immunotherapy with nivolumab that has not been previously reported: the development of a third-degree atrioventricular block. After a second infusion with nivolumab, our patient developed a troponin I-positive and autoantibody-positive myositis and a few days later a new-onset third-degree atrioventricular block. This is most likely because of an autoimmune-induced myositis with a cardiac impairment in terms of a myocarditis, which led to an impairment of the conduction of cardiac electrical stimuli.

25 Article Preferences of German melanoma patients for interferon (IFN) α-2b toxicities (the DeCOG "GERMELATOX survey") versus melanoma recurrence to quantify patients' relative values for adjuvant therapy. 2016

Kaehler, Katharina C / Blome, Christine / Forschner, Andrea / Gutzmer, Ralf / Haalck, Thomas / Heinzerling, Lucie / Kornek, Thomas / Livingstone, Elisabeth / Loquai, Carmen / Maul, Lara Valeska / Lang, Berenice M / Schadendorf, Dirk / Stade, Barbara / Terheyden, Patrick / Utikal, Jochen / Wagner, Tobias / Hauschild, Axel / Garbe, Claus / Augustin, Matthias. ·aDepartment of Dermatology, University Hospital Schleswig-Holstein (UKSH), Campus Kiel, Kiel bInstitute for Health Services Research in Dermatology and Nursing (IVDP), University Medical Center Hamburg, Hamburg cDepartment of Dermatology, Eberhard-Karls University of Tuebingen, Tuebingen dSkin Cancer Center Hannover, Hannover eUniversity of Hamburg, Hamburg fDepartment of Dermatology, University Hospital Erlangen, Erlangen gTABEA Clinic, Hamburg hDepartment of Dermatology, University Hospital Essen, Essen iDepartment of Dermatology, University of Mainz, Mainz jMSD Sharp & Dohme GmbH, Munich kDepartment of Dermatology, University Hospital (UKSH), Campus Lübeck, Luebeck lSkin Cancer Unit, German Cancer Research Center (DKFZ) mDepartment of Dermatology, Venereology and Allergology, University Medical Center Mannheim, Ruprecht-Karl University of Heidelberg, Heidelberg, Germany. ·Medicine (Baltimore) · Pubmed #27861370.

ABSTRACT: Currently interferon alfa-2b (IFNα-2b) is an approved adjuvant drug for high-risk melanoma patients that leads to an improvement in disease-free survival (DFS). However, it is unclear whether it also impacts overall survival. Widespread use of adjuvant high-dose IFNα has been tempered by its significant toxicity and its limited efficacy. Current therapeutic strategies like immune checkpoint blockade or targeted therapy may also be useful in the adjuvant setting. Therefore, it is important to weigh the trade-offs between possible side effects and therapeutic benefit.We assessed patient utilities for health states associated with IFN therapy. Utilities are measures of preference for a specific health state on a scale of 0 (death) to 1 (perfect health).Utilities were determined for health states associated with adjuvant IFN among 130 German low-risk melanoma patients using the standard gamble technique. Four IFNα-2b toxicity scenarios and the following 3 posttreatment outcomes were assessed: disease-free health and melanoma recurrence (with or without previous use of IFNα-2b) resulting in cancer death. Patients were asked to trade-off the improvement in 5-year DFS and the IFN-related side effects.Utilities for melanoma recurrence (mean 0.60) were significantly lower than for all IFNα-2b toxicity scenarios (mean 0.81-0.90). Patients were willing to tolerate mild-to-moderate and severe toxicity for a 50% and 75% chance of 5-year DFS, respectively. Both utilities and threshold benefits were mostly independent from patient characteristics like gender, income, and social situation. Significant impact was only observed by age and previous personal experience with cancer.On average, German patients were willing to trade even severe IFNα-2b toxicity for reducing the rate of melanoma recurrence. This result points out the importance of a relapse-free survival for melanoma patients. The utilities measured in our study can be applied to decision-making processes in clinical trials of new adjuvant drugs.

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