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Melanoma: HELP
Articles from Elbe Klinikum
Based on 32 articles published since 2010
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These are the 32 published articles about Melanoma that originated from Elbe Klinikum during 2010-2020.
 
+ Citations + Abstracts
Pages: 1 · 2
1 Review Epidemiological evidence of carcinogenicity of sunbed use and of efficacy of preventive measures. 2019

Gandini, S / Doré, J-F / Autier, P / Greinert, R / Boniol, M. ·Molecular and Pharmaco-Epidemiology Unit, Department of Experimental Oncology, European Institute of Oncology, IRCCS, Milan, Italy. · Centre de Recherche en Cancérologie de Lyon, Inserm U1052, Lyon, France. · International Prevention Research Institute, Lyon, France. · Department of Molecular Cell biology, Dermatology Center Buxtehude, Elbekliniken Stade/Buxtehude, Klinikum Buxtehude, Buxtehude, Germany. ·J Eur Acad Dermatol Venereol · Pubmed #30811691.

ABSTRACT: The International Agency for Research on Cancer classified, in July 2009, exposure to artificial tanning devices (sunbeds) as carcinogenic to humans. This classification was based on evidence from epidemiological and experimental animal studies. The present chapter will review these epidemiological evidences. The summary risk estimates from 27 epidemiological studies obtained through a meta-analysis showed an increased risk of melanoma: summary relative risk (SRR) = 1.20 [95% confidence interval (CI) 1.08-1.34]. The risk was higher when exposure took place at younger age (SRR = 1.59; 95% CI 1.36-1.85). The risk was independent of skin sensitivity or population and a dose response was evident. A meta-analysis of 12 studies was conducted for non-melanoma skin cancers and showed a significantly increased risk for basal cell carcinoma (SRR = 1.29; 95% CI 1.08-1.53) and for squamous cell carcinoma (SRR = 1.67; 95% CI 1.29-2.17). As for melanoma, the risk for other skin cancers increased for first exposures at young age. Epidemiological studies have gradually strengthened the evidence for a causal relationship between indoor tanning and skin cancer and they fit with prior knowledge on relationship between UV exposure and skin cancer. Additionally, several case-control studies provided consistent evidence of a positive association between use of sunbed and ocular melanoma, also with greater risk for first exposures at younger age. Preventive measures based on information on risk or by requiring parental authorization for young users proved to be inefficient in several studies. The significant impact of strong actions or total ban, such as performed in Iceland, or a total ban of sunbed use, as in Brazil or Australian states, needs to be further assessed.

2 Review ECCO essential requirements for quality cancer care: Melanoma. 2018

Wouters, Michel W / Michielin, Olivier / Bastiaannet, Esther / Beishon, Marc / Catalano, Orlando / Del Marmol, Veronique / Delgado-Bolton, Roberto / Dendale, Rémi / Trill, Maria Die / Ferrari, Andrea / Forsea, Ana-Maria / Kreckel, Hannelore / Lövey, József / Luyten, Gre / Massi, Daniela / Mohr, Peter / Oberst, Simon / Pereira, Philippe / Prata, João Paulo Paiva / Rutkowski, Piotr / Saarto, Tiina / Sheth, Sapna / Spurrier-Bernard, Gilly / Vuoristo, Meri-Sisko / Costa, Alberto / Naredi, Peter. ·European Society of Surgical Oncology (ESSO); Department of Surgery, Netherlands Cancer Institute, Amsterdam, The Netherlands. · European Society for Medical Oncology (ESMO); Department of Oncology, CHUV, University Hospital of Lausanne, Lausanne, Switzerland. · International Society of Geriatric Oncology (SIOG); Department of Surgery/Department of Medical Oncology, Leiden University Medical Centre, Leiden, The Netherlands. · European School of Oncology (ESO), Milan, Italy. · European Society of Radiology (ESR); Department of Radiology, National Cancer Institute Fondazione Pascale, Naples, Italy. · Association of European Cancer Leagues (ECL); Euromelanoma, European Academy of Dermatology and Venereology (EADV); Department of Dermatology and Venereology, Erasme Hospital, ULB, Brussels, Belgium. · European Association of Nuclear Medicine (EANM); Department of Diagnostic Imaging (Radiology) and Nuclear Medicine, San Pedro Hospital and Centre for Biomedical Research of La Rioja (CIBIR), University of La Rioja, Logroño, La Rioja, Spain. · European Society for Radiotherapy and Oncology (ESTRO); Radiation Oncology Department, Institut Curie, Paris, France. · International Psycho-Oncology Society (IPOS); ATRIUM: Psycho-Oncology & Clinical Psychology, Madrid, Spain. · European Society for Paediatric Oncology (SIOPE); Pediatric Oncology Unit, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy. · European Association of Dermato Oncology (EADO); Dermatology Department, Elias University Hospital, Carol Davila University of Medicine and Pharmacy, Bucharest, Romania. · European Society of Oncology Pharmacy (ESOP); Pharmacy Department, University Hospital Giessen and Marburg, Giessen, Germany. · Organisation of European Cancer Institutes (OECI); National Institute of Oncology, Budapest, Hungary. · Ocular Oncology Group (OOG); Department of Ophthalmology, Leiden University Medical Center, Leiden, The Netherlands. · European Society of Pathology (ESP); Division of Pathological Anatomy, Department of Surgery and Translational Medicine, University of Florence, Florence, Italy. · European Society of Skin Cancer Prevention (EUROSKIN); Elbe-Klinikum Buxtehude, Buxtehude, Germany. · Organisation of European Cancer Institutes (OECI); Cambridge Cancer Centre, Cambridge, UK. · Cardiovascular and Interventional Radiological Society of Europe (CIRSE); Clinic for Radiology, Minimally-Invasive Therapies and Nuclear Medicine, SLK-Clinics Heilbronn, Karl-Ruprecht-University of Heidelberg, Heilbronn, Germany. · European Oncology Nursing Society (EONS); Instituto Português de Oncologia de Lisboa Francisco Gentil, Lisbon, Portugal. · European Organisation for Research and Treatment of Cancer (EORTC); Maria Sklodowska-Curie Institute - Oncology Center, Warsaw, Poland. · European Association for Palliative Care (EAPC); Comprehensive Cancer Center, Department of Palliative Care, University of Helsinki and Helsinki University Hospital, Helsinki, Finland. · European CanCer Organisation, Brussels, Belgium. · European CanCer Organisation (ECCO) Patient Advisory Committee; Melanoma Patient Network Europe; Paris, France. · Association of European Cancer Leagues (ECL); Pirkanmaa Cancer Society, Tampere, Finland. · European CanCer Organisation (ECCO); Department of Surgery, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden. Electronic address: peter.naredi@gu.se. ·Crit Rev Oncol Hematol · Pubmed #29458785.

ABSTRACT: BACKGROUND: ECCO essential requirements for quality cancer care (ERQCC) are explanations and descriptions of challenges, organisation and actions that are necessary to give high-quality care to patients who have a specific type of cancer. They are written by European experts representing all disciplines involved in cancer care. ERQCC papers give oncology teams, patients, policymakers and managers an overview of the elements needed in any healthcare system to provide high quality of care throughout the patient journey. References are made to clinical guidelines and other resources where appropriate, and the focus is on care in Europe. MELANOMA: ESSENTIAL REQUIREMENTS FOR QUALITY CARE: CONCLUSION: Taken together, the information presented in this paper provides a comprehensive description of the essential requirements for establishing a high-quality service for melanoma. The ERQCC expert group is aware that it is not possible to propose a 'one size fits all' system for all countries, but urges that access to multidisciplinary teams and specialised treatments is guaranteed to all patients with melanoma.

3 Review Checkpoint-Inhibitoren in der Immuntherapie: Ein Meilenstein in der Behandlung des malignen Melanoms. 2016

Wilden, Sophia M / Lang, Berenice M / Mohr, Peter / Grabbe, Stephan. ·Hautklinik der Universitätsmedizin, Mainz. · Hautklinik, Elbekliniken Buxtehude. ·J Dtsch Dermatol Ges · Pubmed #27373243.

ABSTRACT: Seit Jahrzehnten ist bekannt, dass Tumoren vom Immunsystem erkannt und zerstört werden können. Diese, vor allem in Tierversuchen gewonnene Erkenntnis konnte jedoch in der Vergangenheit nicht zum Nutzen unserer Patienten umgesetzt werden, da immunonkologische Therapieansätze in den letzten Jahrzehnten in der Anwendung beim Menschen stets versagt haben. Daher hat, mit Ausnahme der adjuvanten Interferontherapie, keines dieser Verfahren den Einzug in die klinische Versorgung gefunden. Langzeitüberleben unter guter Lebensqualität war dabei sehr wenigen Patienten vorbehalten. Mit den neuen immunologischen Therapieansätzen wird jedoch sowohl das Langzeitüberleben als auch die Lebensqualität onkologischer Patienten neu definiert. Auf die neuen "Immun-Checkpoint-Inhibitoren" spricht erstmals ein relevanter Teil der behandelten Patienten an und diese zeigen in der Regel langandauernde Remissionen bis hin zur Heilung. Schon jetzt ist klar, dass die Immuntherapie in Zukunft eine der wesentlichen Therapiesäulen bei der Behandlung des metastasierten Melanoms und auch vieler anderer fortgeschrittener Tumoren bilden wird. In dieser Übersicht werden die wichtigsten neuen Therapiemodalitäten besprochen und sowohl deren Wirkprinzip als auch klinische Daten zum Therapieansprechen und zu erwartenden Nebenwirkungen der Therapie referiert.

4 Review Immune checkpoint inhibitors: a milestone in the treatment of melanoma. 2016

Wilden, Sophia M / Lang, Berenice M / Mohr, Peter / Grabbe, Stephan. ·Department of Dermatology, University Medical Center Mainz, Mainz, Germany. · Department of Dermatology, Elbe Hospital, Buxtehude, Germany. ·J Dtsch Dermatol Ges · Pubmed #27373242.

ABSTRACT: It has been known for decades that the immune system is able to detect and destroy tumor cells. In the past, this knowledge - mostly acquired through animal experiments - could not be used to benefit our patients, because immuno-oncological therapeutic approaches in humans had constantly failed over recent decades. With the exception of adjuvant interferon therapy, none of these approaches had found its way into everyday clinical practice, and only very few patients were able to enjoy long-term survival associated with good quality of life. With the advent of novel immunological approaches, the meaning of long-term survival as well as quality of life has been redefined for oncological patients. For the first time, a significant percentage of patients responds to treatment with immune checkpoint inhibitors, showing long-term remission and even cure. It has already become apparent that immunotherapy will in the future be one of the therapeutic mainstays in the treatment of metastatic melanoma as well as many other tumor types. The present review article presents the most important new treatment modalities, their mechanism of action, clinical data regarding treatment response, and adverse events to be expected.

5 Clinical Trial Dabrafenib plus trametinib versus dabrafenib monotherapy in patients with metastatic BRAF V600E/K-mutant melanoma: long-term survival and safety analysis of a phase 3 study. 2017

Long, G V / Flaherty, K T / Stroyakovskiy, D / Gogas, H / Levchenko, E / de Braud, F / Larkin, J / Garbe, C / Jouary, T / Hauschild, A / Chiarion-Sileni, V / Lebbe, C / Mandalà, M / Millward, M / Arance, A / Bondarenko, I / Haanen, J B A G / Hansson, J / Utikal, J / Ferraresi, V / Mohr, P / Probachai, V / Schadendorf, D / Nathan, P / Robert, C / Ribas, A / Davies, M A / Lane, S R / Legos, J J / Mookerjee, B / Grob, J-J. ·Melanoma Institute Australia, The University of Sydney, and Royal North Shore and Mater Hospitals, North Sydney, Australia. · Developmental Therapeutics and Melanoma Programs, Massachusetts General Hospital Cancer Center, Boston, USA. · Moscow City Oncology Hospital #62, Moscow, Russia. · First Department of Medicine, "Laiko" General Hospital, National and Kapodistrian University of Athens, Athens, Greece. · Petrov Research Institute of Oncology, Saint Petersburg, Russia. · Dipartimento di Medicina Oncologica, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy. · Royal Marsden NHS Foundation Trust, London, UK. · Department of Dermatology, University of Tübingen, Tübingen, Germany. · Service D'oncologie Médicale, Hopital Francois Mitterrand, Pau, France. · Department of Dermatology, University Hospital Schleswig-Holstein, Kiel, Germany. · Melanoma and Oesophageal Oncology Unit, Veneto Oncology Institute-IRCCS, Padova, Italy. · APHP Dermatology and CIC Departments, INSERM U976, University Paris Diderot, Paris, France. · Department of Oncology and Hematology, Papa Giovanni XXIII Hospital, Bergamo, Italy. · Medical Oncology Department, Sir Charles Gairdner Hospital, Perth, Australia. · Department of Medical Oncology, Hospital Clinic of Barcelona, Barcelona, Spain. · Dnipropetrovsk State Medical Academy, Clinical Hospital #4, Dnipropetrovsk, Ukraine. · Netherlands Cancer Institute, Amsterdam, The Netherlands. · Department of Oncology-Pathology, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden. · Skin Cancer Unit, German Cancer Research Center (DKFZ) and Department of Dermatology, Venereology and Allergology, University Medical Center Mannheim, Ruprecht-Karls University of Heidelberg, Mannheim and Heidelberg, Germany. · Department of Medical Oncology A, Regina Elena National Cancer Institute, Rome, Italy. · Dermatologisches Zentrum Buxtehude, Elbe Kliniken Buxtehude, Buxtehude, Germany. · Dnipropetrovsk Clinical Oncology Center of Dnipropetrovsk State Council, Dnipropetrovsk, Ukraine. · Department of Dermatology, University Hospital Essen, Essen, Germany. · German Cancer Consortium, Heidelberg, Germany. · Mount Vernon Cancer Centre, Northwood, UK. · Gustave Roussy, Département de Médecine Oncologique, Service de Dermatologie et Université Paris-Sud, Faculté de Médecine, Villejuif, France. · Department of Medicine, Hematology/Oncology, UCLA Jonsson Comprehensive Cancer Center, Los Angeles, USA. · Melanoma Medical Oncology and Systems Biology, The University of Texas MD Anderson Cancer Center, Houston, USA. · Novartis Pharmaceuticals Corporation, East Hanover, USA. · Service de Dermatologie, Centre Hospitalo-Universitaire Timone, Aix-Marseille Université, Marseille, France. ·Ann Oncol · Pubmed #28475671.

ABSTRACT: Background: Previous analysis of COMBI-d (NCT01584648) demonstrated improved progression-free survival (PFS) and overall survival (OS) with combination dabrafenib and trametinib versus dabrafenib monotherapy in BRAF V600E/K-mutant metastatic melanoma. This study was continued to assess 3-year landmark efficacy and safety after ≥36-month follow-up for all living patients. Patients and methods: This double-blind, phase 3 study enrolled previously untreated patients with BRAF V600E/K-mutant unresectable stage IIIC or stage IV melanoma. Patients were randomized to receive dabrafenib (150 mg twice daily) plus trametinib (2 mg once daily) or dabrafenib plus placebo. The primary endpoint was PFS; secondary endpoints were OS, overall response, duration of response, safety, and pharmacokinetics. Results: Between 4 May and 30 November 2012, a total of 423 of 947 screened patients were randomly assigned to receive dabrafenib plus trametinib (n = 211) or dabrafenib monotherapy (n = 212). At data cut-off (15 February 2016), outcomes remained superior with the combination: 3-year PFS was 22% with dabrafenib plus trametinib versus 12% with monotherapy, and 3-year OS was 44% versus 32%, respectively. Twenty-five patients receiving monotherapy crossed over to combination therapy, with continued follow-up under the monotherapy arm (per intent-to-treat principle). Of combination-arm patients alive at 3 years, 58% remained on dabrafenib plus trametinib. Three-year OS with the combination reached 62% in the most favourable subgroup (normal lactate dehydrogenase and <3 organ sites with metastasis) versus only 25% in the unfavourable subgroup (elevated lactate dehydrogenase). The dabrafenib plus trametinib safety profile was consistent with previous clinical trial observations, and no new safety signals were detected with long-term use. Conclusions: These data demonstrate that durable (≥3 years) survival is achievable with dabrafenib plus trametinib in patients with BRAF V600-mutant metastatic melanoma and support long-term first-line use of the combination in this setting.

6 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.

7 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.

8 Clinical Trial Nivolumab versus chemotherapy in patients with advanced melanoma who progressed after anti-CTLA-4 treatment (CheckMate 037): a randomised, controlled, open-label, phase 3 trial. 2015

Weber, Jeffrey S / D'Angelo, Sandra P / Minor, David / Hodi, F Stephen / Gutzmer, Ralf / Neyns, Bart / Hoeller, Christoph / Khushalani, Nikhil I / Miller, Wilson H / Lao, Christopher D / Linette, Gerald P / Thomas, Luc / Lorigan, Paul / Grossmann, Kenneth F / Hassel, Jessica C / Maio, Michele / Sznol, Mario / Ascierto, Paolo A / Mohr, Peter / Chmielowski, Bartosz / Bryce, Alan / Svane, Inge M / Grob, Jean-Jacques / Krackhardt, Angela M / Horak, Christine / Lambert, Alexandre / Yang, Arvin S / Larkin, James. ·Moffitt Cancer Center, Tampa, FL, USA. Electronic address: jeffrey.weber@moffitt.org. · Memorial Sloan-Kettering Cancer Center and Weill Cornell Medical College, New York, NY, USA. · California Pacific Center for Melanoma Research, San Francisco, CA, USA. · Dana-Farber Cancer Institute, Boston, MA, USA. · Medizinische Hochschule Hannover, Hannover, Germany. · Universitair Ziekenhuis Brussel, Brussels, Belgium. · Medical University of Vienna, Vienna, Austria. · Roswell Park Cancer Institute, Buffalo, NY, USA. · Segal Cancer Centre, Jewish General Hospital, McGill University, Montreal, QC, Canada. · University of Michigan, Ann Arbor, MI, USA. · Washington University, St Louis, MO, USA. · Centre Hospitalier Universitaire de Lyon, Lyon, France. · Christie Hospital, Manchester, UK. · Huntsman Cancer Institute, Salt Lake City, UT, USA. · German Cancer Research Centre University Hospital, Heidelberg, Germany. · Medical Oncology and Immunotherapy, University Hospital of Siena, Istituto Toscano Tumori, Siena, Italy. · Yale Cancer Center, New Haven, CT, USA. · Istituto Nazionale Tumori Fondazione G Pascale, Naples, Italy. · Elbe Kliniken Buxtehude, Buxtehude, Germany. · Department of Medicine, University of California, Los Angeles, CA, USA. · Department of Medicine, Mayo Clinic, Scottsdale, AZ, USA. · Department of Oncology, Herlev Hospital, Copenhagen, Denmark. · Aix-Marseille University, Hopital de la Timone, Marseille, France. · Technische Universität München School of Medicine, II Medical Department, Munich, Germany. · Bristol-Myers Squibb, Princeton, NJ, USA. · Bristol-Myers Squibb, Braine-I'Alleud, Belgium. · Royal Marsden Hospital, London, UK. ·Lancet Oncol · Pubmed #25795410.

ABSTRACT: BACKGROUND: Nivolumab, a fully human IgG4 PD-1 immune checkpoint inhibitor antibody, can result in durable responses in patients with melanoma who have progressed after ipilimumab and BRAF inhibitors. We assessed the efficacy and safety of nivolumab compared with investigator's choice of chemotherapy (ICC) as a second-line or later-line treatment in patients with advanced melanoma. METHODS: In this randomised, controlled, open-label, phase 3 trial, we recruited patients at 90 sites in 14 countries. Eligible patients were 18 years or older, had unresectable or metastatic melanoma, and progressed after ipilimumab, or ipilimumab and a BRAF inhibitor if they were BRAF(V 600) mutation-positive. Participating investigators randomly assigned (with an interactive voice response system) patients 2:1 to receive an intravenous infusion of nivolumab 3 mg/kg every 2 weeks or ICC (dacarbazine 1000 mg/m(2) every 3 weeks or paclitaxel 175 mg/m(2) combined with carboplatin area under the curve 6 every 3 weeks) until progression or unacceptable toxic effects. We stratified randomisation by BRAF mutation status, tumour expression of PD-L1, and previous best overall response to ipilimumab. We used permuted blocks (block size of six) within each stratum. Primary endpoints were the proportion of patients who had an objective response and overall survival. Treatment was given open-label, but those doing tumour assessments were masked to treatment assignment. We assessed objective responses per-protocol after 120 patients had been treated with nivolumab and had a minimum follow-up of 24 weeks, and safety in all patients who had had at least one dose of treatment. The trial is closed and this is the first interim analysis, reporting the objective response primary endpoint. This study is registered with ClinicalTrials.gov, number NCT01721746. FINDINGS: Between Dec 21, 2012, and Jan 10, 2014, we screened 631 patients, randomly allocating 272 patients to nivolumab and 133 to ICC. Confirmed objective responses were reported in 38 (31·7%, 95% CI 23·5-40·8) of the first 120 patients in the nivolumab group versus five (10·6%, 3·5-23·1) of 47 patients in the ICC group. Grade 3-4 adverse events related to nivolumab included increased lipase (three [1%] of 268 patients), increased alanine aminotransferase, anaemia, and fatigue (two [1%] each); for ICC, these included neutropenia (14 [14%] of 102), thrombocytopenia (six [6%]), and anaemia (five [5%]). We noted grade 3-4 drug-related serious adverse events in 12 (5%) nivolumab-treated patients and nine (9%) patients in the ICC group. No treatment-related deaths occurred. INTERPRETATION: Nivolumab led to a greater proportion of patients achieving an objective response and fewer toxic effects than with alternative available chemotherapy regimens for patients with advanced melanoma that has progressed after ipilimumab or ipilimumab and a BRAF inhibitor. Nivolumab represents a new treatment option with clinically meaningful durable objective responses in a population of high unmet need. FUNDING: Bristol-Myers Squibb.

9 Article KEYNOTE-716: Phase III study of adjuvant pembrolizumab versus placebo in resected high-risk stage II melanoma. 2020

Luke, Jason J / Ascierto, Paolo A / Carlino, Matteo S / Gershenwald, Jeffrey E / Grob, Jean-Jacques / Hauschild, Axel / Kirkwood, John M / Long, Georgina V / Mohr, Peter / Robert, Caroline / Ross, Merrick / Scolyer, Richard A / Yoon, Charles H / Poklepovic, Andrew / Rutkowski, Piotr / Anderson, James R / Ahsan, Sama / Ibrahim, Nageatte / M Eggermont, Alexander M. ·Cancer Immunotherapeutics Center, UPMC Hillman Cancer Center, University of Pittsburgh, Pittsburgh, PA 15232, USA. · Melanoma, Cancer Immunotherapy and Development Therapeutics Unit, Istituto Nazionale Tumori IRCCS "Fondazione G. Pascale," Naples, Italy. · Department of Medical Oncology, Crown Princess Mary Cancer Centre, Westmead Hospital, Westmead, NSW, Australia. · Blacktown Cancer and Haematology Centre, Blacktown Hospital, Blacktown, NSW, Australia. · Melanoma Institute Australia, Sydney, NSW, Australia. · Sydney Medical School, The University of Sydney, Sydney, NSW, Australia. · Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA. · Department of Dermatology and Skin Cancers, Hôpital de la Timone, Aix-Marseille Université, Marseille, France. · Department of Dermatological Oncology, University Hospital Schleswig-Holstein, Kiel, Germany. · Department of Medical Oncology, Mater Hospital, North Sydney, NSW, Australia. · Department of Medical Oncology, Royal North Shore Hospital, St Leonards, NSW, Australia. · Department of Dermatology, Elbe Kliniken Buxtehude, Buxtehude, Germany. · Dermatology Unit, Department of Oncology, Gustave Roussy Cancer Centre, Villejuif, France. · Department of Medicine, Université Paris-Sud, Orsay, France. · Department of Medicine, Royal Prince Alfred Hospital, Sydney, NSW, Australia. · Department of Surgical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA. · Department of Internal Medicine, VCU Massey Cancer Center, Richmond, VA 23298, USA. · Department of Soft Tissue/Bone Sarcoma and Melanoma, Maria Sklodowska-Curie Institute - Oncology Center, Warsaw, Poland. · Department of Clinical Oncology, Merck & Co., Inc., Kenilworth, NJ 07033, USA. · Department of Medical Oncology, Gustave Roussy Cancer Institute & Université Paris-Saclay, Paris, France. ·Future Oncol · Pubmed #31870188.

ABSTRACT: Patients with high-risk stage II melanoma are at significant risk for recurrence after surgical resection. Adjuvant treatment options to lower the risk for distant metastases are limited. Although adjuvant IFN-α2b is associated with improved relapse-free survival in patients with high-risk melanoma, toxicity and limited overall survival benefits limit its use. Adjuvant treatment with the PD-1 inhibitor pembrolizumab significantly improved recurrence-free survival, compared with placebo, in patients with resected stage III melanoma in the Phase III KEYNOTE-054 trial; efficacy in patients with stage II disease has not been established. This article describes the design and rationale of KEYNOTE-716 (NCT03553836), a two-part, randomized, placebo-controlled, multicenter Phase III study of adjuvant pembrolizumab in patients with surgically resected high-risk stage II melanoma. Clinical trial registry & ID: ClinicalTrials.gov, NCT03553836.

10 Article Intra-Patient Heterogeneity of Circulating Tumor Cells and Circulating Tumor DNA in Blood of Melanoma Patients. 2019

Gorges, Katharina / Wiltfang, Lisa / Gorges, Tobias M / Sartori, Alexander / Hildebrandt, Lina / Keller, Laura / Volkmer, Beate / Peine, Sven / Babayan, Anna / Moll, Ingrid / Schneider, Stefan W / Twarock, Sören / Mohr, Peter / Fischer, Jens W / Pantel, Klaus. ·Institute for Pharmacology and Clinical Pharmacology, University Hospital of the Heinrich-Heine-University, 40225 Düsseldorf, Germany. roeck@hhu.de. · Department of Tumor Biology, University Medical Center Hamburg-Eppendorf, 20251 Hamburg, Germany. l.wiltfang@uke.de. · Department of Tumor Biology, University Medical Center Hamburg-Eppendorf, 20251 Hamburg, Germany. t.gorges@uke.de. · Agena Bioscience GmbH, 22761 Hamburg, Germany. alexander.sartori@agenabio.com. · Department of Dermatology, University Medical Center Hamburg-Eppendorf, 20251 Hamburg, Germany. l.hildebrandt@uke.de. · Department of Tumor Biology, University Medical Center Hamburg-Eppendorf, 20251 Hamburg, Germany. l.keller@uke.de. · Department of Dermatology, Elbe Kliniken, 21614 Buxtehude, Germany. beate.volkmer@elbekliniken.de. · Institute of Transfusion Medicine, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany. s.peine@uke.de. · Department of Tumor Biology, University Medical Center Hamburg-Eppendorf, 20251 Hamburg, Germany. a.babayan@uke.de. · DermatoMed, 22303 Hamburg, Germany. dermatomed@arztzentrum.de. · Department of Dermatology, University Medical Center Hamburg-Eppendorf, 20251 Hamburg, Germany. st.schneider@uke.de. · Institute for Pharmacology and Clinical Pharmacology, University Hospital of the Heinrich-Heine-University, 40225 Düsseldorf, Germany. soeren.twarock@hhu.de. · Department of Dermatology, Elbe Kliniken, 21614 Buxtehude, Germany. peter.mohr@elbekliniken.de. · Institute for Pharmacology and Clinical Pharmacology, University Hospital of the Heinrich-Heine-University, 40225 Düsseldorf, Germany. jens.fischer@uni-duesseldorf.de. · Department of Tumor Biology, University Medical Center Hamburg-Eppendorf, 20251 Hamburg, Germany. pantel@uke.de. ·Cancers (Basel) · Pubmed #31671846.

ABSTRACT: Despite remarkable progress in melanoma therapy, the exceptional heterogeneity of the disease has prevented the development of reliable companion biomarkers for the prediction or monitoring of therapy responses. Here, we show that difficulties in detecting blood-based markers, like circulating tumor cells (CTC), might arise from the translation of the mutational heterogeneity of melanoma cells towards their surface marker expression. We provide a unique method, which enables the molecular characterization of clinically relevant CTC subsets, as well as circulating tumor DNA (ctDNA), from a single blood sample. The study demonstrates the benefit of a combined analysis of ctDNA and CTC counts in melanoma patients, revealing that CTC subsets and ctDNA provide synergistic real-time information on the mutational status, RNA and protein expression of melanoma cells in individual patients, in relation to clinical outcome.

11 Article [Social rights claims for malignant melanoma patients : Providing patient information in German dermatological practices]. 2019

Zander, N / Krensel, M / Schäfer, I / Weyergraf, A / Mohr, P / Strömer, K / Augustin, M. ·Institut für Versorgungsforschung in der Dermatologie und bei Pflegeberufen (IVDP), Universitätsklinikum Hamburg-Eppendorf (UKE), 20246, Hamburg, Deutschland. n.zander@uke.de. · Institut für Versorgungsforschung in der Dermatologie und bei Pflegeberufen (IVDP), Universitätsklinikum Hamburg-Eppendorf (UKE), 20246, Hamburg, Deutschland. · Klinik für Dermatologie und Allergologie, Fachklinik Bad Bentheim, Bad Bentheim, Deutschland. · Hautkrebszentrum Buxtehude, Elbe Kliniken Stade/Buxtehude, Buxtehude, Deutschland. · Berufsverband der Deutschen Dermatologen, Berlin, Deutschland. ·Hautarzt · Pubmed #31267179.

ABSTRACT: BACKGROUND: Treatment of patients with malignant melanoma includes informing the patients about their rights regarding social/disability benefits. In particular, every patient has the right to rehabilitation treatment according to SGB V and IX (SGB: Sozialgesetzbuch; Social Security Code) and to an examination regarding the classification of the disability. OBJECTIVES: The present study examines the extent to which patients with invasive malignant melanoma are informed after initial diagnosis about their social rights to medical rehabilitation measures and the classification of disability. MATERIALS AND METHODS: In the course of a survey in 2014, n = 1800 German dermatological practices were contacted and provided a standardized questionnaire on several care-relevant questions, including the aforementioned ones. RESULTS: Evaluable questionnaires were submitted by n = 424 practices. In all, 52% of dermatologists stated that they regularly provided information on the right to rehabilitation, 15% sometimes, 41% rarely or never. Furthermore, 44% of dermatologists regularly, 17% sometimes and 38% rarely or never informed their patients about the classification of disability. Relevant differences were found in regional comparisons. CONCLUSIONS: Practicing dermatologists seem to transfer the information requirement to the clinics involved in the treatment. It would be beneficial if the information were also provided again by the dermatologists in private practice. In view of the known limited capacity to receive new information from patients with newly diagnosed melanoma, repeated counselling appears to be more patient-friendly.

12 Article Real-World Use of Talimogene Laherparepvec in German Patients with Stage IIIB to IVM1a Melanoma: A Retrospective Chart Review and Physician Survey. 2019

Mohr, Peter / Haferkamp, Sebastian / Pinter, Andreas / Weishaupt, Carsten / Huber, Margit A / Downey, Gerald / Öhrling, Katarina / Loquai, Carmen / Louie, Karly S. ·Department of Dermatology, Elbe-Klinikum Buxtehude, Buxtehude, Germany. peter.mohr@elbekliniken.de. · Department of Dermatology, University Hospital Regensburg, Regensburg, Germany. · Department of Dermatology, Venereology and Allergology, University Hospital Frankfurt, Frankfurt am Main, Germany. · Department of Dermatology, University Hospital of Muenster, Muenster, Germany. · Department of Dermatology and Allergic Diseases, Ulm University, Ulm, Germany. · Amgen Ltd, Cambridge, UK. · Amgen Europe GmbH, Rotkreuz, Switzerland. · Department of Dermatology, University Medical Center Mainz, Mainz, Germany. · Amgen Ltd, Uxbridge, UK. ·Adv Ther · Pubmed #30536143.

ABSTRACT: INTRODUCTION: Talimogene laherparepvec is a first-in-class oncolytic immunotherapy for intratumoral injection with proven efficacy and tolerability in patients with unresectable early metastatic melanoma (stage IIIB-IVM1a) in the pivotal phase III OPTiM study. The objective was to characterize melanoma patients treated with talimogene laherparepvec in routine clinical practice in Germany. METHODS: A retrospective chart review was conducted in unresectable stage IIIB-IVM1a melanoma patients. Data on demographics, disease and medical history, and use of talimogene laherparepvec were collected. A survey was also conducted to understand physician treatment decisions. RESULTS: Data for 27 patients who initiated talimogene laherparepvec between June 2016 and July 2017 were analyzed (median age 68; stage IIIB/C disease 56%). All patients had prior surgery, and over half had repeated resections for recurrent disease (median 3). Overall, 48% of patients received at least one prior local treatment, mainly radiation therapy or electrochemotherapy. Talimogene laherparepvec was first-line systemic therapy in 63% of patients. The most frequent prior systemic treatment was immunotherapy (7/27 patients). At end of follow-up, 13 patients were still on talimogene laherparepvec and 14 patients had discontinued treatment. Among those who discontinued, 8 (57%) did not receive subsequent systemic therapy. Only one patient receiving first-line talimogene laherparepvec received a subsequent systemic therapy. Three patients stopped treatment because of no remaining injectable lesions. Median treatment duration was 22.1 weeks overall and 27.9 weeks in stage IIIB/C disease patients. Nearly all cutaneous lesions (93%) were injected with talimogene laherparepvec compared to subcutaneous (83%) and nodal lesions (77%). No new safety signals were reported. The main reasons given in the physician survey for treating with talimogene laherparepvec were good tolerability, overall efficacy, and lack of contraindications. CONCLUSION: Talimogene laherparepvec is now included as a routine treatment option for unresectable early metastatic melanoma in Germany. This study characterizes the first patients treated with talimogene laherparepvec in Europe and confirms the good tolerability observed in clinical trials. TRIAL REGISTRATION: EUPAS registry, EUPAS17410. FUNDING: Amgen Inc.

13 Article Advanced cutaneous squamous cell carcinoma: A retrospective analysis of patient profiles and treatment patterns-Results of a non-interventional study of the DeCOG. 2018

Hillen, Uwe / Leiter, Ulrike / Haase, Sylvie / Kaufmann, Roland / Becker, Jürgen / Gutzmer, Ralf / Terheyden, Patrick / Krause-Bergmann, Albrecht / Schulze, Hans-Joachim / Hassel, Jessica / Lahner, Nina / Wollina, Uwe / Ziller, Fabian / Utikal, Jochen / Hafner, Christine / Ulrich, Jens / Machens, Hans-Günther / Weishaupt, Carsten / Hauschild, Axel / Mohr, Peter / Pföhler, Claudia / Maurer, Jan / Wolff, Patrick / Windemuth-Kieselbach, Christine / Schadendorf, Dirk / Livingstone, Elisabeth / Anonymous28210943. ·Department of Dermatology, University Hospital Essen, University Duisburg-Essen, 45147 Essen, Germany; Department of Dermatology and Venerology, Vivantes Klinikum Neukölln, 12351 Berlin, Germany. Electronic address: uwe.hillen@vivantes.de. · Department of Dermatology, University Hospital Tübingen, 72076 Tübingen, Germany. · Department of Dermatology, University Hospital Frankfurt, 60590 Frankfurt, Germany; Hautärzte in Konstanz, 78462 Konstanz, Germany. · Department of Dermatology, University Hospital Frankfurt, 60590 Frankfurt, Germany. · Department of Dermatology, University Hospital Graz, 8036 Graz, Austria; Translational Skin Cancer Research, German Cancer Consortium (DKTK), Partner Site Essen/Düsseldorf, Essen, Germany; German Cancer Research Center (DKFZ), Heidelberg, Germany. · Skin Cancer Center, Department of Dermatology and Allergy, Hannover Medical School, 30625 Hannover, Germany. · Department of Dermatology, University Hospital Schleswig-Holstein, Campus Lübeck, 23538 Lübeck, Germany. · Department of Plastic Surgery, Fachklinik Hornheide, 48157 Münster, Germany. · Department of Dermatology, Fachklinik Hornheide, 48157 Münster, Germany. · Department of Dermatology, University Hospital Heidelberg, 69120 Heidelberg, Germany. · Department of Dermatology, Ruhr-University Bochum, 44791 Bochum, Germany. · Department of Dermatology, University Hospital Dresden, 01067 Dresden, Germany. · Department of Dermatology, DRK Krankenhaus Rabenstein, 09117 Chemnitz, 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. · Dept. of Dermatology, University Hospital St. Pölten, Karl Landsteiner University of Health Sciences, 3500 St. Pölten, Austria; Karl Landsteiner Institute of Dermatological Research, Karl Landsteiner Gesellschaft, 3500 St. Pölten, Austria. · Department of Dermatology, Harzklinikum Dorothea Christiane Erxleben, 06484 Quedlinburg, Germany. · Department of Plastic Surgery and Hand Surgery, Klinikum Rechts der Isar, Technische Universität München, 81675 Munich, Germany. · Department of Dermatology, University Hospital Münster, 48149 Münster, Germany. · Department of Dermatology, University Hospital Schleswig-Holstein, Campus Kiel, 24105 Kiel, Germany. · Department of Dermatology, Elbe-Kliniken, 21614 Buxtehude, Germany. · Department of Dermatology, Saarland University Medical School, 66421 Homburg/Saar, Germany. · Department of ENT, Katholisches Klinikum Marienhof, 56073 Koblenz, Germany. · Alcedis GmbH, Medical Research Institute, 35394 Gießen, Germany. · Department of Dermatology, University Hospital Essen, University Duisburg-Essen, 45147 Essen, Germany; Translational Skin Cancer Research, German Cancer Consortium (DKTK), Partner Site Essen/Düsseldorf, Essen, Germany. · Department of Dermatology, University Hospital Essen, University Duisburg-Essen, 45147 Essen, Germany. ·Eur J Cancer · Pubmed #29665511.

ABSTRACT: BACKGROUND: Advanced cutaneous squamous cell carcinoma (aSCC) is an area of unmet medical need and no treatment standards are established. Recently, an anti-PD-1 inhibitor received FDA breakthrough therapy designation. The aim of the study was to describe the clinical course, therapeutic management and prognosis of aSCC under real-life conditions. PATIENTS AND METHODS: In a retrospective study performed in 24 German and Austrian hospitals and doctor's offices, patient and tumour characteristics of patients diagnosed with aSCC between January 1, 2010 and December 31, 2011 and their disease course was documented. Advanced SCC comprised either locally advanced SCCs (laSCC) or metastatic SCCs (mSCC) with any kind of metastatic spread. RESULTS: Data of 190 patients with aSCC were analysed. Median age at time of diagnosis of aSCC was 78 years. LaSCC was diagnosed in 76 patients (40%), 114 patients (60%) had mSCC. Once diagnosed with laSCC, most patients (59%) did not receive any therapy, whereas in 92% of mSCC patients at least one type of therapy was performed. Only 32 patients (29 mSCC, 3 laSCC) received systemic antitumour therapies, mostly EGFR inhibitor-based regimens. Mean duration of response was short (17-months laSCC patients, 3-months mSCC patients). Only 2 patients achieved a complete response, 27% had a partial response, 43% disease stabilisation. At diagnosis of aSCC, ECOG status was 0-1 in most patients. Non-malignant comorbidities influenced the decision on SCC-specific therapy in 39 patients (21%). CONCLUSIONS: Our data show the high medical need for efficient and tolerable antitumour therapies and demonstrate that despite older age and comorbidities, most patients can be expected to be fit for treatment. This study provides a historical context for emerging aSCC treatments.

14 Article PD-L1 status does not predict the outcome of BRAF inhibitor therapy in metastatic melanoma. 2018

Schaper-Gerhardt, Katrin / Okoye, Steven / Herbst, Rudolf / Ulrich, Jens / Terheyden, Patrick / Pföhler, Claudia / Utikal, Jochen S / Kreuter, Alexander / Mohr, Peter / Dippel, Edgar / Satzger, Imke / Sucker, Antje / Schadendorf, Dirk / Ugurel, Selma / Gutzmer, Ralf. ·Skin Cancer Center Hannover, Dept. of Dermatology and Allergy, Hannover Medical School, Carl Neuberg Str. 1, 30625 Hannover, Germany. Electronic address: schaper-gerhardt.katrin@mh-hannover.de. · Skin Cancer Center Hannover, Dept. of Dermatology and Allergy, Hannover Medical School, Carl Neuberg Str. 1, 30625 Hannover, Germany. Electronic address: okoye.steven@mh-hannover.de. · Department of Dermatology, Helios Clinic, Erfurt, Germany. Electronic address: rudolf.herbst@helios-kliniken.de. · Department of Dermatology, Quedlinburg, Germany. Electronic address: jens.ulrich@harzklinikum.com. · Department of Dermatology, University of Lübeck, Lübeck, Germany. Electronic address: Patrick.terheyden@uksh.de. · Department of Dermatology, Saarland University Medical School, Homburg, Germany. Electronic address: Claudia.pfoehler@uks.eu. · Skin Cancer Unit, German Cancer Research Center (DKFZ) and Department of Dermatology, Venereology and Allergology, University Medical Center Mannheim, Ruprecht-Karl University of Heidelberg, 68167 Mannheim, Germany. Electronic address: j.utikal@dkfz-heidelberg.de. · Department of Dermatology, Venereology, and Allergology, HELIOS St. Elisabeth Hospital Oberhausen, University Witten-Herdecke, Germany. Electronic address: alexander.kreuter@helios-kliniken.de. · Department of Dermatology, Elbe Clinic, Buxtehude, Germany. Electronic address: Peter.Mohr@elbekliniken.de. · Department of Dermatology, Ludwigshafen Hospital, Ludwigshafen, Germany. Electronic address: Dippele@klilu.de. · Skin Cancer Center Hannover, Dept. of Dermatology and Allergy, Hannover Medical School, Carl Neuberg Str. 1, 30625 Hannover, Germany. Electronic address: Satzger.imke@mh-hannover.de. · Department of Dermatology, University of Duisburg-Essen, Essen, Germany. Electronic address: antje.sucker@uk-essen.de. · Department of Dermatology, University of Duisburg-Essen, Essen, Germany. Electronic address: dirk.schadendorf@uk-essen.de. · Department of Dermatology, University of Duisburg-Essen, Essen, Germany. Electronic address: selma.ugurel@uk-essen.de. · Skin Cancer Center Hannover, Dept. of Dermatology and Allergy, Hannover Medical School, Carl Neuberg Str. 1, 30625 Hannover, Germany. Electronic address: Gutzmer.ralf@mh-hannover.de. ·Eur J Cancer · Pubmed #29195116.

ABSTRACT: BACKGROUND: Targeted therapies with BRAF plus MEK inhibitors (BRAFi; MEKi) represent the major treatment strategy for patients with BRAF-mutated metastatic melanoma (MM). Previous analyses suggested a correlation between programmed death-ligand 1 (PD-L1) expression in tumour tissues and the outcome of targeted therapies. This study investigated PD-L1 as a potential predictive biomarker of BRAFi-based targeted therapies in MM patients. PATIENTS AND METHODS: We analysed two independent cohorts of BRAF V600-mutated MM patients undergoing BRAFi-based therapies for PD-L1 expression in pre-treatment tumour tissues. The oligocentre cohort 1 included 83 patients whose tumour tissues were analysed retrospectively with the anti-PD-L1 antibody clone E1L3N. The multicentre cohort 2 included 58 patients whose tumour tissues were analysed prospectively within the framework of the "Registry of the Arbeitsgemeinschaft Dermatologische Onkologie" (ADOREG) and "Tissue Registry in Melanoma" (TRIM) project using the anti-PD-L1 antibody clone 28-8. RESULTS: PD-L1 expression in pre-treatment tumour tissue did not correlate with response or survival to BRAFi-based therapies in both MM patient cohorts. This finding was not influenced by retrospective versus prospective immunohistochemistry analyses, oligocentre versus multicentre cohorts or the different anti-PD-L1 antibody clones used. In cohort 1, PD-L1 positivity was detected in tumour tissue of 41.0% and 18.1% of patients (cut-off 1% and 5%, respectively). In cohort 2, 58.6% and 39.7% of patients showed PD-L1 positivity (cut-off 1% and 5%, respectively). CONCLUSION: In two independent cohorts including a total of 141 MM patients, PD-L1 expression in tumour tissue did not correlate with the outcome of BRAFi-based treatment. Therefore, PD-L1 cannot be recommended for the use as a predictive biomarker of BRAFi-based therapy in BRAF V600-mutated MM.

15 Article Real-world treatment patterns and outcomes among metastatic cutaneous melanoma patients treated with ipilimumab. 2018

Mohr, P / Ascierto, P / Arance, A / McArthur, G / Hernaez, A / Kaskel, P / Shinde, R / Stevinson, K. ·Elbe-Klinikum Buxtehude, Buxtehude, Germany. · Istituto Nazionale Tumori Fondazione Pascale, Naples, Italy. · Hospital Clinic Barcelona, Barcelona, Spain. · Peter MacCallum Cancer Centre, East Melbourne, Vic., Australia. · University of Melbourne, Parkville, Vic., Australia. · Mapi, Stockholm, Sweden. · MSD SHARP & DOHME GMBH, Haar, Germany. · Merck & Co. Inc., Kenilworth, NJ, USA. ·J Eur Acad Dermatol Venereol · Pubmed #29044660.

ABSTRACT: BACKGROUND: There is a scarcity of real-world data on treatment patterns and outcomes among advanced melanoma patients treated with immunotherapies including ipilimumab, an anti-CTLA-4 antibody approved since 2011. OBJECTIVE: To evaluate ipilimumab and postipilimumab treatment patterns and outcomes among patients with advanced melanoma in Australia, Germany, Italy and Spain, following regulatory approval. METHODS: Retrospective multicentre, multinational, observational chart review study. Data were extracted from the start of ipilimumab therapy until the end of at least 40 weeks of follow-up, or death. RESULTS: Data from 371 patients (Australia, 103; Germany, 152; Italy, 76; Spain, 40) were analysed. Mean age was 65 years; 62% were male. Eastern Cooperative Oncology Group performance status (ECOG PS) was 0 or 1 for 94%. In 67%, ipilimumab was initially received as second-line or later therapy. Patients received on average 3.4 ipilimumab doses. The ipilimumab-refractory cohort comprised of 226 patients. Of these, 17% in Australia, 47% in Germany, 29% in Italy and 14% in Spain received another antimelanoma treatment after ipilimumab including chemotherapy in 26% and BRAF/other kinase inhibitors in 11%. Ipilimumab-refractory patients who received postipilimumab treatment showed a 40% reduced hazard of dying than those not receiving treatment after ipilimumab (HR 0.60; 95% CI 0.43-0.83), after adjustment for potential confounders. CONCLUSION: During the time observed, ipilimumab was mainly used as second-line or later therapy. A significant proportion of patients received postipilimumab therapy, most of which was chemotherapy. Nevertheless, overall survival following progression on ipilimumab treatment remained poor, highlighting the need for research to develop more effective end-of-life treatment options.

16 Article Association between risk factors and detection of cutaneous melanoma in the setting of a population-based skin cancer screening. 2018

Hübner, Joachim / Waldmann, Annika / Eisemann, Nora / Noftz, Maria / Geller, Alan C / Weinstock, Martin A / Volkmer, Beate / Greinert, Rüdiger / Breitbart, Eckhard W / Katalinic, Alexander. ·Institute of Social Medicine and Epidemiology. · Department of Social and Behavioral Sciences, Harvard T.H. Chan School of Public Health, Boston, Massachusetts. · Center for Dermatoepidemiology, VA Medical Center Providence. · Department of Dermatology, Rhode Island Hospital, Providence. · Departments of Dermatology and Epidemiology, Brown University, Providence, Rhode Island, USA. · Dermatology Center, Division of Molecular Cell Biology, Elbe Clinics Stade-Buxtehude, Buxtehude. · Association of Dermatological Prevention e.V., Hamburg, Germany. · Institute of Cancer Epidemiology, University of Lübeck, Lübeck, Germany. ·Eur J Cancer Prev · Pubmed #28692584.

ABSTRACT: Early detection is considered to improve the prognosis of cutaneous melanoma. The value of population-based screening for melanoma, however, is still controversial. The aim of this study was to evaluate the predictive power of established risk factors in the setting of a population-based screening and to provide empirical evidence for potential risk stratifications. We reanalyzed data (including age, sex, risk factors, and screening results) of 354 635 participants in the Skin Cancer Research to provide Evidence for Effectiveness of Screening in Northern Germany (SCREEN)project conducted in the German state of Schleswig-Holstein (2003-2004). In multivariable analysis, atypical nevi [odds ratio (OR): 17.4; 95% confidence interval (CI): 14.4-20.1], personal history of melanoma (OR: 5.3; 95% CI: 3.6-7.6), and multiple (≥40) common nevi (OR: 1.3; 95% CI: 1.1-1.6) were associated with an increased risk of melanoma detection. Family history and congenital nevi were not significantly associated with melanoma detection in the SCREEN. The effects of several risk-adapted screening strategies were evaluated. Hypothesizing a screening of individuals aged more than or equal to 35 years, irrespective of risk factors (age approach), the number needed to screen is 559 (95% CI: 514-612), whereas a screening of adults (aged ≥20) with at least one risk factor (risk approach) leads to a number needed to screen of 178 (95% CI: 163-196). Converted into one screen-detected melanoma, the number of missed melanomas is 0.15 (95% CI: 0.12-0.18) with the age approach and 0.22 (95% CI: 0.19-0.26) with the risk approach. The results indicate that focusing on individuals at high risk for melanoma may improve the cost-effectiveness and the benefit-to-harm balance of melanoma screening programs.

17 Article Economic burden of advanced melanoma in France, Germany and the UK: a retrospective observational study (Melanoma Burden-of-Illness Study). 2017

Grange, Florent / Mohr, Peter / Harries, Mark / Ehness, Rainer / Benjamin, Laure / Siakpere, Obukohwo / Barth, Janina / Stapelkamp, Ceilidh / Pfersch, Sylvie / McLeod, Lori D / Kaye, James A / Wolowacz, Sorrel / Kontoudis, Ilias. ·aDepartment of Dermatology, Reims University Hospital, Reims bGSK France, Marly le Roi cedex, France cClinic of Dermatology, Elbekliniken Buxtehude, Buxtehude dGSK GmbH & Co KG, Munich, Germany eDepartment of Medical Oncology, Guy's and St Thomas's Hospitals NHS, Foundation Trust, Guy's Hospital, London fGSK UK, Middlesex gHealth Economics, RTI Health Solutions, The Pavilion, Towers Business Park, Manchester, UK hPatient-Centered Outcomes Assessment, RTI Health Solutions, Research Triangle Park, North Carolina iDepartment of Epidemiology, RTI Health Solutions, Waltham, Massachusetts, USA jGSK Vaccines, Rue de l'Institut, Rixensart, Belgium. ·Melanoma Res · Pubmed #28800027.

ABSTRACT: The aim of this study was to estimate the cost-of-illness associated with completely resected stage IIIB/IIIC melanoma with macroscopic lymph node involvement, overall and by disease phase, in France, Germany and the UK. This retrospective observational study included patients aged older than or equal to 18 years first diagnosed with stage IIIB/IIIC cutaneous melanoma between 1 January 2009 and 31 December 2011. Data were obtained from medical records and a patient survey. Direct costs, indirect costs and patient out-of-pocket expenses were estimated in euros (€) (and British pounds, £) by collecting resource use and multiplying by country-specific unit costs. National annual costs were estimated using national disease prevalence from the European cancer registry and other published data. Forty-nine centres provided data on 558 patients (58.2% aged <65 years, 53.6% stage IIIB disease at diagnosis). The mean follow-up duration was 27 months (France), 26 months (Germany) and 22 months (UK). The mean total direct cost per patient during follow-up was €23 582 in France, €32 058 in Germany and €37 970 (£31 123) in the UK. The largest cost drivers were melanoma drugs [mean €14 004, €21 269, €29 750 (£24 385), respectively] and hospitalization/emergency treatment [mean: €6634, €6950, €3449 (£2827), respectively]. The total mean indirect costs per patient were €129 (France), €4,441 (Germany) and €1712 (£1427) (UK). Estimates for annual national direct cost were €13.1 million (France), €30.2 million (Germany) and €27.8 (£22.8) million (UK). The economic burden of stage IIIB/IIIC melanoma with macroscopic lymph node involvement was substantial in all three countries. Total direct costs were the highest during the period with distant metastasis/terminal illness.

18 Article Association of atopy and tentative diagnosis of skin cancer - results from occupational skin cancer screenings. 2017

Schäfer, I / Mohr, P / Zander, N / Fölster-Holst, R / Augustin, M. ·German Center for Health Services Research in Dermatology (CVderm), Institute for Health Services Research in Dermatology and Nursing (IVDP), University Medical Center Hamburg-Eppendorf (UKE), Hamburg, Germany. · Department of Dermatology, Elbe Kliniken Buxtehude, Buxtehude, Germany. · Department of Dermatology, University of Kiel, Kiel, Germany. ·J Eur Acad Dermatol Venereol · Pubmed #28681396.

ABSTRACT: BACKGROUND: The relationship between atopic conditions and carcinoma of the skin has been described inconsistently. Population-based data providing information on atopic diseases as well as on skin cancer are sparse. OBJECTIVE: To determine the correlation between atopy and prevalence of precanceroses, non-melanoma skin cancer and malignant melanoma (MM), while taking into account known risk factors for skin cancer. METHODS: Data from occupational skin cancer screenings were analysed in a cross-sectional study. Dermatologists performed whole body examinations and collected medical histories. Subjects comprised all employees (16-70 years) examined from 2006 to 2014. 'Atopy' was defined by clinical screening diagnosis and/or by participant-reported, pre-existing atopic dermatitis, allergic asthma or other specified allergies confirmed by a physician. Tentative screening diagnoses of skin cancer related to actinic keratosis, basal cell carcinoma and malignant melanoma. RESULTS: The study cohort comprised 90 265 employees (mean age 43 ± 11 years, 58.5% male), 30.7% of whom were ever diagnosed with an atopic disease. Persons with atopic conditions recorded in their medical history and at the time of screening had a significantly lower prevalence of actinic keratosis (AK), basal cell carcinoma (BCC) and MM. After controlling for age, sex and relevant risk factors (skin type, childhood sun burns), atopy remained significantly protective against BCC (OR 0.77) and MM (OR 0.53). CONCLUSION: Design limitations of the study include that all findings of skin cancer were based on clinical examination only and must therefore be considered tentative diagnoses. Furthermore, owing to the cross-sectional study design, causal pathways cannot be proven. However, analyses of data from such a large and general population-based cohort afford valuable insights into the relationship between atopic diseases and skin cancer. They provide the grounds for prospective cohort studies to evaluate and dissect the underlying mechanism.

19 Article Health Care Resource Utilization and Associated Costs Among Metastatic Cutaneous Melanoma Patients Treated with Ipilimumab (INTUITION Study). 2017

McArthur, Grant A / Mohr, Peter / Ascierto, Paolo Antonio / Arance, Ana / Banos Hernaez, Ana / Kaskel, Peter / Weichenthal, Michael / Shinde, Reshma / Stevinson, Kendall. ·Peter MacCallum Cancer Centre, East Melbourne, Australia. · Elbe-Klinikum Buxtehude, Buxtehude, Germany. · Istituto Nazionale Tumori Fondazione Pascale, Naples, Italy. · Hospital Clinic Barcelona, Barcelona, Spain. · Mapi, Stockholm, Sweden. · MSD Sharp & Dohme GmbH, Haar, Germany. · Universitäts-Hautklinik Kiel, Kiel, Germany. · Merck & Co., Inc., Kenilworth, New Jersey, USA. · Merck & Co., Inc., Kenilworth, New Jersey, USA kendall_stevinson@merck.com. ·Oncologist · Pubmed #28526721.

ABSTRACT: BACKGROUND: There are limited real-world data on health care resource utilization (HCRU) among advanced melanoma patients. The objective of this study was to describe HCRU and health care costs associated with the management of advanced melanoma patients receiving ipilimumab. METHODS: This retrospective multinational, observational study included advanced melanoma patients from Australia, Germany, Italy, and Spain who had received at least 1 dose of ipilimumab. Data extracted from medical charts included inpatient admissions, outpatient visits, surgical procedures, laboratory investigations, radiation therapy, imaging studies, and concomitant medications. Cost estimates were based on unit costs from country-specific standard reimbursement sources. Subgroup analyses were performed for BRAF mutation status and ipilimumab refractory patients, who had disease progression within 24 weeks of their last dose of ipilimumab. RESULTS: Mean age of 362 enrolled patients was 60.6 years (standard deviation [SD] 14.4). During a median follow-up period of 30.2 weeks, 57% of patients were admitted to hospital and 16% underwent surgery. Health care resource utilization rates varied substantially across countries and were highest in Germany. Concomitant medications to treat adverse events were commonly used. Subgroup analyses showed higher utilization rates among ipilimumab refractory and BRAF mutant patients. Mean weekly total costs associated with HCRU were lower in the pre-progression period (€107; 95% confidence interval (CI): 79-145) than in the post-progression period (€216; 95% CI: 180-259). CONCLUSION: Health care resource utilization pattern and associated costs among patients treated with ipilimumab varied greatly among countries and between pre- and post-progression periods. There is a high economic burden associated with ipilimumab refractory melanoma. IMPLICATIONS FOR PRACTICE: Metastatic melanoma patients treated with the anti-CTLA-4 inhibitor ipilimumab have a high utilization of various types of health care services, such as inpatient hospital stays or doctor visits. There are differences across countries regarding patterns of health care utilization and economic burden of the disease. Health care services are used more frequently after patients experience progression of their disease. The study highlights that better therapies leading to durable response in patients with metastatic melanoma have the potential to decrease health care costs and patient burden in terms of hospitalizations and other health care services.

20 Article Treatment patterns and outcomes of Stage IIIB/IIIC melanoma in France, Germany and the UK: A retrospective and prospective observational study (MELABIS). 2017

Harries, Mark / Mohr, Peter / Grange, Florent / Ehness, Rainer / Benjamin, Laure / Siakpere, Obukohwo / Barth, Janina / Stapelkamp, Ceilidh / Pfersch, Sylvie / McLeod, Lori / Wolowacz, Sorrel / Kaye, James A / Kontoudis, Ilias. ·Department of Medical Oncology, Guy's and St Thomas's Hospitals NHS Foundation Trust, Guy's Hospital, London, UK. · Clinic of Dermatology, Elbekliniken Buxtehude, Buxtehude, Germany. · Dermatology, Reims University Hospital, Reims, France. · GSK GmbH & Co KG, Munich, Germany. · GSK France, 78163 Marly le Roi cedex, France. · GSK UK, Middlesex, UK. · Patient Reported Outcomes, RTI Health Solutions, Research Triangle Park, NC, USA. · Health Economics, RTI Health Solutions, The Pavilion, Towers Business Park, Wilmslow Road Manchester, Manchester, UK. · Epidemiology, RTI Health Solutions, Waltham, MA, USA. · GSK, Rue de l'Institut, Rixensart, Belgium. ·Int J Clin Pract · Pubmed #28508460.

ABSTRACT: AIM: Real-world data on treatment patterns/outcomes in patients with advanced melanoma, while scarce, are useful for health technology assessments that govern patient access in many countries. We collected retrospective data on treatment patterns among patients in France, Germany and the UK with Stage IIIB/IIIC melanoma with macroscopic lymph node involvement, whose primary melanoma and regional lymph node metastases had been completely resected. METHODS: Patients ≥18 years were diagnosed between 1 January 2009 and 31 December 2011. Data were obtained from patients' medical records and a patient survey. RESULTS: Forty-nine centres provided data on 558 patients: 53.6% had Stage IIIB disease; 58.2% were of working age (<65 years), 22.5% reported a change in employment status due to melanoma, 8% were on long-term sick leave; and 35.1% were deceased over the study period. Overall median distant metastases-free survival was 23.4 months and median disease-free survival was 13.3 months. Hospitalisation frequency increased during distant metastatic/terminal disease phases. Adjuvant therapy was received by 7.0% (14/199) of patients in France, 2.6% (5/195) in the UK, and 33.5% (55/164) in Germany. Low-dose interferon was used more frequently than other regimens. High-dose interferon was associated with discontinuation in 28.6% and dose delay/reduction in 33.3% of patients. CONCLUSIONS: Rapid disease progression combined with increased use of healthcare resources in later phases of disease result in a high burden-of-illness for patients and healthcare providers. The use of adjuvant interferon therapy varies considerably in this population in the countries studied, highlighting the need for improved treatments for melanoma.

21 Article Targeted next generation sequencing of mucosal melanomas identifies frequent NF1 and RAS mutations. 2017

Cosgarea, Ioana / Ugurel, Selma / Sucker, Antje / Livingstone, Elisabeth / Zimmer, Lisa / Ziemer, Mirjana / Utikal, Jochen / Mohr, Peter / Pfeiffer, Christiane / Pföhler, Claudia / Hillen, Uwe / Horn, Susanne / Schadendorf, Dirk / Griewank, Klaus G / Roesch, Alexander. ·Department of Dermatology, University Hospital Essen, West German Cancer Center, University Duisburg-Essen and the German Cancer Consortium (DKTK), University of Duisburg-Essen, Duisburg/Essen, Germany. · Department of Dermatology, Venereology and Allergology, University Hospital Leipzig, Germany. · Skin Cancer Unit, German Cancer Research Center (DKFZ), Heidelberg and Department of Dermatology, Venereology and Allergology, University Medical Center Mannheim, Ruprecht-Karl University of Heidelberg, Mannheim, Germany. · Department of Dermatology, Elbe Klinikum Buxtehude, Buxtehude, Germany. · Department of Dermatology, Klinikum Augsburg, Augsburg, Germany. · Department of Dermatology, Saarland University Medical School, Homburg/Saar, Germany. ·Oncotarget · Pubmed #28380455.

ABSTRACT: PURPOSE: Mucosal melanoma represents ~1% of all melanomas, frequently having a poor prognosis due to diagnosis at a late stage of disease. Mucosal melanoma differs from cutaneous melanoma not only in terms of poorer clinical outcome but also on the molecular level having e.g. less BRAF and more frequent KIT mutations than cutaneous melanomas. For the majority of mucosal melanomas oncogenic driver mutations remain unknown. EXPERIMENTAL DESIGN AND RESULTS: In our study, 75 tumor tissues from patients diagnosed with mucosal melanoma were analyzed, applying a targeted next generation sequencing panel covering 29 known recurrently mutated genes in melanoma. NF1 and RAS mutations were identified as the most frequently mutated genes occurring in 18.3% and 16.9% of samples, respectively. Mutations in BRAF were identified in 8.4% and KIT in 7.0% of tumor samples. CONCLUSIONS: Our study identifies NF1 as the most frequently occurring driver mutation in mucosal melanoma. RAS alterations, consisting of NRAS and KRAS mutations, were the second most frequent mutation type. BRAF and KIT mutations were rare with frequencies below 10% each. Our data indicate that in mucosal melanomas RAS/NF1 alterations are frequent, implying a significant pathogenetic role for MAPK and potentially PI3K pathway activation in these tumors.

22 Article Efficacy and Safety of Nivolumab Alone or in Combination With Ipilimumab in Patients With Mucosal Melanoma: A Pooled Analysis. 2017

D'Angelo, Sandra P / Larkin, James / Sosman, Jeffrey A / Lebbé, Celeste / Brady, Benjamin / Neyns, Bart / Schmidt, Henrik / Hassel, Jessica C / Hodi, F Stephen / Lorigan, Paul / Savage, Kerry J / Miller, Wilson H / Mohr, Peter / Marquez-Rodas, Ivan / Charles, Julie / Kaatz, Martin / Sznol, Mario / Weber, Jeffrey S / Shoushtari, Alexander N / Ruisi, Mary / Jiang, Joel / Wolchok, Jedd D. ·Sandra P. D'Angelo, Alexander N. Shoushtari, and Jedd D. Wolchok, Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York, NY · James Larkin, Royal Marsden Hospital, London · Paul Lorigan, University of Manchester, Manchester, United Kingdom · Jeffrey A. Sosman, Vanderbilt University Medical Center, Nashville, TN · Celeste Lebbé, Saint-Louis Hospital, Institut National de la Santé et de la Recherche Médicale U976, Université Paris Diderot, Paris · Julie Charles, Grenoble University Hospital, Grenoble Alps University, Grenoble, France · Benjamin Brady, Cabrini Health, Melbourne, Australia · Bart Neyns, Universitair Ziekenhuis Brussel, Brussels, Belgium · Henrik Schmidt, Århus University, Åarhus, Denmark · Jessica C. Hassel, University Hospital Heidelberg, Heidelberg · Peter Mohr, Elbe Kliniken Buxtehude, Buxtehude · Martin Kaatz, SRH Waldklinikum Gera, University Hospital Jena, Jena, Germany · F. Stephen Hodi, Dana-Farber Cancer Institute, Boston, MA · Kerry J. Savage, BC Cancer Agency, University of British Columbia, Vancouver · Wilson H. Miller Jr, Lady Davis Institute and Jewish General Hospital, McGill University, Montreal, Canada · Ivan Marquez-Rodas, Hospital General Universitario Gregorio Marañón, Madrid, Spain · Mario Sznol, Yale University School of Medicine and Smilow Cancer Center, Yale-New Haven Hospital, New Haven, CT · Jeffrey S. Weber, Moffitt Cancer Center, Tampa, FL · and Mary Ruisi and Joel Jiang, Bristol-Myers Squibb, Princeton, NJ. ·J Clin Oncol · Pubmed #28056206.

ABSTRACT: Purpose Mucosal melanoma is an aggressive malignancy with a poor response to conventional therapies. The efficacy and safety of nivolumab (a programmed death-1 checkpoint inhibitor), alone or combined with ipilimumab (a cytotoxic T-lymphocyte antigen-4 checkpoint inhibitor), have not been reported in this rare melanoma subtype. Patients and Methods Data were pooled from 889 patients who received nivolumab monotherapy in clinical studies, including phase III trials; 86 (10%) had mucosal melanoma and 665 (75%) had cutaneous melanoma. Data were also pooled for patients who received nivolumab combined with ipilimumab (n = 35, mucosal melanoma; n = 326, cutaneous melanoma). Results Among patients who received nivolumab monotherapy, median progression-free survival was 3.0 months (95% CI, 2.2 to 5.4 months) and 6.2 months (95% CI, 5.1 to 7.5 months) for mucosal and cutaneous melanoma, with objective response rates of 23.3% (95% CI, 14.8% to 33.6%) and 40.9% (95% CI, 37.1% to 44.7%), respectively. Median progression-free survival in patients treated with nivolumab combined with ipilimumab was 5.9 months (95% CI, 2.8 months to not reached) and 11.7 months (95% CI, 8.9 to 16.7 months) for mucosal and cutaneous melanoma, with objective response rates of 37.1% (95% CI, 21.5% to 55.1%) and 60.4% (95% CI, 54.9% to 65.8%), respectively. For mucosal and cutaneous melanoma, respectively, the incidence of grade 3 or 4 treatment-related adverse events was 8.1% and 12.5% for nivolumab monotherapy and 40.0% and 54.9% for combination therapy. Conclusion To our knowledge, this is the largest analysis of data for anti-programmed death-1 therapy in mucosal melanoma to date. Nivolumab combined with ipilimumab seemed to have greater efficacy than either agent alone, and although the activity was lower in mucosal melanoma, the safety profile was similar between subtypes.

23 Article Interval cancers after skin cancer screening: incidence, tumour characteristics and risk factors for cutaneous melanoma. 2017

Hübner, J / Waldmann, A / Geller, A C / Weinstock, M A / Eisemann, N / Noftz, M / Bertram, S / Nolte, S / Volkmer, B / Greinert, R / Breitbart, E / Katalinic, A. ·Institute for Social Medicine and Epidemiology, University of Lübeck, Ratzeburger Allee 160, Lübeck 23562, Germany. · Department of Social and Behavioral Sciences, Harvard T.H. Chan School of Public Health, 677 Huntington Avenue, Boston, MA 02115, USA. · Center for Dermatoepidemiology, VA Medical Center-111D, 830 Chalkstone Avenue, Providence, RI 02908, USA. · Department of Dermatology, Rhode Island Hospital, 593 Eddy Street, Providence, RI 02903, USA. · Departments of Dermatology and Epidemiology, Brown University, 593 Eddy Street, Providence, RI 02903, USA. · Department of Psychosomatic Medicine, Center for Internal Medicine and Dermatology, Charité-Universitätsmedizin Berlin, Charitéplatz 1, Berlin 10117, Germany. · Population Health Strategic Research Centre, Deakin University, 221 Burwood Highway, Melbourne, VIC 3125, Australia. · Division of Molecular Cell Biology, Dermatology Center, Elbe Clinics Stade-Buxtehude, Am Krankenhaus 1, Buxtehude 21614, Germany. · Association of Dermatological Prevention e.V., Cremon 11, Hamburg 20457, Germany. · Cancer Registry of Schleswig-Holstein, Ratzeburger Allee 160, Lübeck 23562, Germany. ·Br J Cancer · Pubmed #27898656.

ABSTRACT: BACKGROUND: The rate of interval cancers is an established indicator for the performance of a cancer-screening programme. METHODS: We examined the incidence, tumour characteristics and risk factors of melanoma interval cancers that occurred in participants of the SCREEN project, which was carried out 2003/2004 in Schleswig-Holstein, Germany. Data from 350 306 SCREEN participants, who had been screened negative for melanoma, were linked to data of the state cancer registry. Melanoma interval cancers were defined as melanomas diagnosed within 4-24 months after SCREEN examination. Results were compared with melanomas of the pre-SCREEN era (1999-2002), extracted from the cancer registry. RESULTS: The overall relative incidence of melanoma interval cancers in terms of observed/expected ratio was 0.93 (95% CI: 0.82-1.05; in situ: 1.61 (1.32-1.95), invasive: 0.71 (0.60-0.84)). Compared with melanomas of the pre-SCREEN era, the interval melanomas were thinner and had a slightly greater proportion of lentigo maligna melanomas whereas nodular melanomas were less frequent. INTERPRETATION: The results indicate a moderate performance of the SCREEN intervention with an excess of in situ melanomas. In part, the findings might be due to specifics of the SCREEN project, in particular a short-term follow-up of patients at high risk for melanoma.

24 Article Use of complementary medicine in metastatic melanoma patients treated with ipilimumab within a clinical trial. 2016

Huebner, Jutta / Mohr, Peter / Simon, Jan-Christoph / Fluck, Michael / Berking, Carola / Zimmer, Lisa / Loquai, Carmen. ·Working Group Integrative -Oncology, Dr. Senckenberg -Chronomedical Institute, J.W. -Goethe University, Frankfurt am Main, Germany. · Department of Dermatology, Elbe Medical Center Buxtehude, Buxtehude, Germany. · Department of Dermatology, Venereology and Allergology, University Hospital Leipzig, Leipzig, Germany. · Department for Medical Oncology, Specialty Medical Center Hornheide, Hornheide, Germany. · Department of Dermatology and Allergology, University Hospital -Munich, Munich, Germany. · Department of Dermatology, University Hospital, University -Duisburg-Essen, Essen, Germany. · Department of Dermatology, -University Hospital Mainz, Mainz, Germany. ·J Dtsch Dermatol Ges · Pubmed #27119474.

ABSTRACT: BACKGROUND AND OBJECTIVES: In Germany, 40-90 % of all cancer patients use complementary and alternative medicine (CAM). So far, no data are available on the use of CAM by melanoma patients. The objective of our study was to gather data on CAM use, sources of information, and goals of patients with metastatic melanoma. PATIENTS AND METHODS: One hundred and fifty-six patients from 25 study centers participated in the DecOG-MM-PAL-Multibasket Study. These individuals were also asked to participate in a side study addressing CAM use. A standardized CAM questionnaire was distributed at defined points during the treatment. RESULTS: Overall, 55 questionnaires from 32 (21 %) melanoma patients were received. Of those, 17 (53 %) stated an interest in CAM, and seven (22 %) actually used CAM. Family and friends were the main source of information (31 %), followed by physicians (19 %). The main reasons for using CAM were boosting the immune system (41 %) and strengthening the body (34 %). Supplements (vitamins and trace elements) were most commonly used (28 %). CONCLUSIONS: A relatively high number of metastatic melanoma patients used CAM despite their participation in a clinical trial. Interactions may be due to biologically based CAM, especially immunomodulatory CAM strategies. In order to avoid risks, communication between physicians and patients should be improved.

25 Article Genomic correlates of response to CTLA-4 blockade in metastatic melanoma. 2015

Van Allen, Eliezer M / Miao, Diana / Schilling, Bastian / Shukla, Sachet A / Blank, Christian / Zimmer, Lisa / Sucker, Antje / Hillen, Uwe / Foppen, Marnix H Geukes / Goldinger, Simone M / Utikal, Jochen / Hassel, Jessica C / Weide, Benjamin / Kaehler, Katharina C / Loquai, Carmen / Mohr, Peter / Gutzmer, Ralf / Dummer, Reinhard / Gabriel, Stacey / Wu, Catherine J / Schadendorf, Dirk / Garraway, Levi A. ·Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA. · Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA. · Center for Cancer Precision Medicine, Dana-Farber Cancer Institute, Boston, MA 02215, USA. · Department of Dermatology, University Hospital, University Duisburg-Essen, 45147 Essen, Germany. · German Cancer Consortium (DKTK), 69121 Heidelberg, Germany. · Department of Medical Oncology, Netherlands Cancer Institute, 1066 CX Amsterdam, Netherlands. · Department of Dermatology, University Hospital Zurich, 8091 Zurich, Switzerland. · Skin Cancer Unit, German Cancer Research Center(DKTK), 69121 Heidelberg, Germany. · Department of Dermatology, Venerology, and Allergology, University Medical Center, Ruprecht-Karls University of Heidelberg, 68167 Mannheim, Germany. · Department of Dermatology, University Hospital, Ruprecht-Karls University of Heidelberg, 69120 Heidelberg, Germany. · Department of Dermatology, University Hospital Tübingen, 72076 Tübingen, Germany. · Department of Dermatology, University Hospital Kiel, 24105 Kiel, Germany. · Department of Dermatology, University Medical Center, 55131 Mainz, Germany. · Department of Dermatology, Elbe-Kliniken, 21614 Buxtehude, Germany. · Department of Dermatology and Allergy, Skin Cancer Center Hannover, Hannover Medical School, 30625 Hannover, Germany. ·Science · Pubmed #26359337.

ABSTRACT: Monoclonal antibodies directed against cytotoxic T lymphocyte-associated antigen-4 (CTLA-4), such as ipilimumab, yield considerable clinical benefit for patients with metastatic melanoma by inhibiting immune checkpoint activity, but clinical predictors of response to these therapies remain incompletely characterized. To investigate the roles of tumor-specific neoantigens and alterations in the tumor microenvironment in the response to ipilimumab, we analyzed whole exomes from pretreatment melanoma tumor biopsies and matching germline tissue samples from 110 patients. For 40 of these patients, we also obtained and analyzed transcriptome data from the pretreatment tumor samples. Overall mutational load, neoantigen load, and expression of cytolytic markers in the immune microenvironment were significantly associated with clinical benefit. However, no recurrent neoantigen peptide sequences predicted responder patient populations. Thus, detailed integrated molecular characterization of large patient cohorts may be needed to identify robust determinants of response and resistance to immune checkpoint inhibitors.

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