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Melanoma: HELP
Articles by Reinhard Dummer
Based on 201 articles published since 2009
(Why 201 articles?)

Between 2009 and 2019, R. Dummer wrote the following 201 articles about Melanoma.
+ Citations + Abstracts
Pages: 1 · 2 · 3 · 4 · 5 · 6 · 7 · 8 · 9
1 Guideline Cutaneous melanoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. 2012

Dummer, R / Hauschild, A / Guggenheim, M / Keilholz, U / Pentheroudakis, G / Anonymous3630737. ·Dermatologische Klinik, UniversitätsSpital Zürich, CH-8091 Zürich, Switzerland. ·Ann Oncol · Pubmed #22997461.

ABSTRACT: -- No abstract --

2 Guideline Updated Swiss guidelines for the treatment and follow-up of cutaneous melanoma. 2011

Dummer, R / Guggenheim, M / Arnold, A W / Braun, R / von Moos, R / Anonymous3550713. ·Department of Dermatology, University Hospital of Zurich, Switzerland. reinhard.dummer@usz.ch ·Swiss Med Wkly · Pubmed #22180245.

ABSTRACT: Melanoma is the most common lethal cutaneous neoplasm. In order to harmonise treatment and follow-up of melanoma patients, guidelines for the management of melanoma in Switzerland were inaugurated in 2001 and revised in 2006. A new classification and recent results in randomised trials necessitated changes concerning staging and modifications of the recommendations of therapy and follow-up.

3 Guideline Melanoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. 2010

Dummer, R / Hauschild, A / Guggenheim, M / Jost, L / Pentheroudakis, G / Anonymous3110663. ·Department of Dermatology, Zürich University Hospital, Switzerland. ·Ann Oncol · Pubmed #20555080.

ABSTRACT: -- No abstract --

4 Editorial Precision medicine and skin cancer therapy: dealing with a moving target. 2014

Dummer, Reinhard. ·Department of Dermatology, University Hospital Zurich, Zurich, Switzerland. ·Curr Opin Oncol · Pubmed #24469023.

ABSTRACT: -- No abstract --

5 Editorial Differential diagnosis of melanocytic lesions and molecular biology. 2011

Dummer, Reinhard / Kerl, Katrin / Mihic, Daniela / Kamarachev, Jivko. · ·Arch Dermatol · Pubmed #21339451.

ABSTRACT: -- No abstract --

6 Review Practical clinical guide on the use of talimogene laherparepvec monotherapy in patients with unresectable melanoma in Europe. 2018

Gutzmer, Ralf / Harrington, Kevin J / Hoeller, Christoph / Lebbé, Celeste / Malvehy, Josep / Öhrling, Katarina / Downey, Gerald / Dummer, Reinhard. ·Haut-Tumour-Zentrum Hannover (HTZH), Klinik für Dermatologie, Allergologie und Venerologie, Medizinische Hochschule Hannover (MHH), Hannover, Germany. · NIHR Biomedical Research Centre, The Institute of Cancer Research, London, UK. · Universitätsklinik für Dermatologie, Medizinische Universität Wien, Wien, Austria. · APHP Dermatology and CIC department INSERM U976, Sorbonne Paris Cité, Université Paris Diderot, Hôpital Saint-Louis, Paris, France. · Hospital Clinic of Barcelona, University of Barcelona, IDIBAPS, CIBER de Enfermedades Raras, FIS del Instituto de Salud Carlos III, Barcelona, Spain. · Medical Development, Amgen (Europe) GmbH, Rotkreuz, Switzerland. · Biostatistics, Amgen Ltd, Cambridge, UK. · Skin Cancer Centre/Dermatology Clinic, Universitätsspital Zürich, Zürich, Switzerland. ·Eur J Dermatol · Pubmed #30698145.

ABSTRACT: Talimogene laherparepvec, a herpes simplex virus type 1-based intralesional oncolytic immunotherapy, is approved in Europe for the treatment of adults with unresectable stage IIIB-IVM1a melanoma, with no bone, brain, lung or other visceral disease. It has direct oncolytic effects in injected lesions, leading to the release of tumour-derived antigens and systemic immune effects mediated by the induction of anti-tumour immunity, which is enhanced by the production of granulocyte macrophage colony-stimulating factor. Responses (which occur in >40% of stage IIIB-IVM1a patients) are often durable (>50% last ≥6 months) and occur in injected and uninjected lesions (in stage IIIB-IVM1c patients, 64%/34% of evaluable injected/uninjected non-visceral lesions, respectively, decreased in size by ≥50%). As with other immunotherapies, responses may be delayed or can arise after pseudoprogression. The pattern of treatment-emergent adverse events is distinct, being mostly grade 1/2, easy to manage, and rarely leading to treatment discontinuation. Systemic therapy represents the backbone of care for many metastatic melanoma patients. Nonetheless, the potential for durable locoregional control with a locally injected agent may make talimogene laherparepvec suitable for selected patients with stage IIIB/C disease, for whom surgery is not possible (e.g. with in-transit metastases, multiple melanoma lesions at different body sites, or those relapsing rapidly after repeated rounds of surgery) and slowly progressing disease. Here, we discuss which patients could be suitable for talimogene laherparepvec monotherapy based on the European indication, review the patterns/timing of response, and discuss the incidence/management of adverse events. Its potential use combined with immune checkpoint inhibitors is also discussed.

7 Review Adjuvant melanoma therapy with new drugs: should physicians continue to focus on metastatic disease or use it earlier in primary melanoma? 2018

Grob, Jean Jacques / Garbe, Claus / Ascierto, Paolo / Larkin, James / Dummer, Reinhard / Schadendorf, Dirk. ·Service de Dermatologie et Cancérologie Cutanée, Aix-Marseille University and APHM University Hospital, Marseille, France. Electronic address: jean-jacques.grob@ap-hm.fr. · Department of Dermatology, University Medical Center, Tuebingen, Germany. · Unit of Medical Oncology and Innovative Therapy, Istituto Nazionale Tumori IRCCS Fondazione G Pascale, Napoli, Italy. · The Royal Marsden NHS Foundation Trust, London, UK. · Department of Dermatology, University Hospital Zurich, Zurich, Switzerland. · Department of Dermatology and Comprehensive Cancer Centre, University Hospital Essen, Essen, Germany. ·Lancet Oncol · Pubmed #30507438.

ABSTRACT: It is important to differentiate between two concepts of adjuvant therapy in melanoma-what we have come to call late adjuvant and early adjuvant therapy. Early adjuvant therapy is defined as a medical intervention that is done after resection of a primary melanoma to eradicate possible undetectable minimal residual disease, whereas late adjuvant therapy is done when an overt metastatic disease (nodal or visceral) has been completely resected, to control disease better than if the same treatment were given at a later time, in the presence of multiple metastases. Early adjuvant therapy is thus a preventive treatment strategy, whereas late adjuvant therapy aims at anticipating treatment of metastatic disease. For patients with melanoma, 1-year treatment with targeted therapies and immunotherapy have only been assessed in late adjuvant settings, the outcomes of which more or less reproduce the same dramatic effect as they have in metastatic disease. However, early adjuvant therapy could provide greater benefits in terms of public health, since thin melanomas without nodal metastases are so common that they account for most deaths by melanoma. In the early adjuvant setting, a treatment course of less than 1 year might be sufficient to control the disease, with less toxicity and at reduced costs. In this Personal View, we discuss the potential benefit of short-term early adjuvant treatment in patients with stage II melanoma, with the hope that sentinel-node biopsy and the American Joint Committee on Cancer staging will soon be replaced by more relevant biomarkers to identify the most suitable candidates for early adjuvant therapy for this disease.

8 Review Development of encorafenib for BRAF-mutated advanced melanoma. 2018

Koelblinger, Peter / Thuerigen, Olaf / Dummer, Reinhard. ·Department of Dermatology, University Hospital of Zurich, Zurich, Switzerland. · Department of Dermatology, Paracelsus Medical University, Salzburg, Austria. · Pierre Fabre Pharma GmbH, Freiburg, Germany. ·Curr Opin Oncol · Pubmed #29356698.

ABSTRACT: PURPOSE OF REVIEW: To describe the pharmacological properties, preclinical and clinical data of the novel V-Raf Murine Sarcoma Viral Oncogene Homolog B (BRAF)-inhibitor encorafenib (LGX818) and to compare these with established BRAF-inhibitors in the treatment of locally advanced or metastatic melanoma. RECENT FINDINGS: Encorafenib has shown improved efficacy in the treatment of metastatic melanoma in comparison with vemurafenib. Combination with the MEK inhibitor (MEKi) binimetinib allows for higher dose intensities of encorafenib further improving response rates (RRs). SUMMARY: Combination therapy with BRAF and MEKi has evolved as a standard of care in the treatment of locally advanced or metastatic BRAF-mutated melanoma. Despite compelling initial RRs, development of treatment resistance eventually leads to tumor progression in the majority of BRAF/MEK-inhibitor treated patients. Moreover, treatment-related adverse events are frequent, resulting in a substantial proportion of dose modifications and/or treatment discontinuations. The second-generation BRAF inhibitor encorafenib has been developed aiming at improved efficacy and tolerability through modifications in pharmacological properties. Clinical phase 3 data show improved progression-free survival both for encorafenib monotherapy and combination therapy with binimetinib compared with vemurafenib. Overall survival data and regulatory approval of this novel substance are eagerly awaited.

9 Review Electrical Impedance Spectroscopy in Skin Cancer Diagnosis. 2017

Braun, Ralph P / Mangana, Johanna / Goldinger, Simone / French, Lars / Dummer, Reinhard / Marghoob, Ashfaq A. ·Department of Dermatology, University Hospital Zürich, Gloriastr 31, 8091 Zürich, Switzerland. Electronic address: Ralph.Braun@usz.ch. · Department of Dermatology, University Hospital Zürich, Gloriastr 31, 8091 Zürich, Switzerland. · Dermatology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, 275 York Avenue, New York, NY 10065, USA. ·Dermatol Clin · Pubmed #28886804.

ABSTRACT: Electrical impedance spectroscopy (EIS) is a noninvasive method that aims to help diagnose skin cancer. The EIS device consists of a handheld probe with a disposable electrode that is applied directly on the skin and uses electrical impendence differences to differentiate between normal and abnormal skin lesions. The EIS algorithm is best used on lesions that are deemed clinically or dermoscopically suspicious and has a high sensitivity in detecting malignant melanoma. The greatest usefulness of EIS is achieved in conjunction with a physician who has experience with this modality and excellent training in the clinical detection of suspicious lesions.

10 Review A review of binimetinib for the treatment of mutant cutaneous melanoma. 2017

Koelblinger, Peter / Dornbierer, Joelle / Dummer, Reinhard. ·Department of Dermatology, University Hospital of Zurich, Zurich, Switzerland. · Department of Dermatology, Paracelsus Medical University, Salzburg, Austria. ·Future Oncol · Pubmed #28587477.

ABSTRACT: Although significant progress has been made in the treatment of unresectable or metastatic melanoma, at least half of all advanced melanoma patients eventually progress and pass away due to their disease. In particular, patients with NRAS-mutated melanoma still face limited therapeutic options, with immunotherapy being the current treatment type of choice. Binimetinib is a selective inhibitor of MEK, a central kinase in the tumor-promoting MAPK pathway. The results of a recent Phase III trial rendered binimetinib the first targeted therapy agent to significantly improve progression-free survival in NRAS-mutated melanoma. This review will summarize the development and clinical data of binimetinib in melanoma in general and also explore the potential future role of this substance as single agent or combination therapy.

11 Review Metastatic melanoma moves on: translational science in the era of personalized medicine. 2017

Levesque, Mitchell P / Cheng, Phil F / Raaijmakers, Marieke I G / Saltari, Annalisa / Dummer, Reinhard. ·Department of Dermatology, University of Zurich, University of Zurich Hospital, Gloriastrasse 31, CH-8091, Zurich, Switzerland. Mitchell.Levesque@usz.ch. · Department of Dermatology, University of Zurich, University of Zurich Hospital, Gloriastrasse 31, CH-8091, Zurich, Switzerland. ·Cancer Metastasis Rev · Pubmed #28321632.

ABSTRACT: Progress in understanding and treating metastatic melanoma is the result of decades of basic and translational research as well as the development of better in vitro tools for modeling the disease. Here, we review the latest therapeutic options for metastatic melanoma and the known genetic and non-genetic mechanisms of resistance to these therapies, as well as the in vitro toolbox that has provided the greatest insights into melanoma progression. These include next-generation sequencing technologies and more complex 2D and 3D cell culture models to functionally test the data generated by genomics approaches. The combination of hypothesis generating and hypothesis testing paradigms reviewed here will be the foundation for the next phase of metastatic melanoma therapies in the coming years.

12 Review Combining talimogene laherparepvec with immunotherapies in melanoma and other solid tumors. 2017

Dummer, Reinhard / Hoeller, Christoph / Gruter, Isabella Pezzani / Michielin, Olivier. ·Department of Dermatology, University of Zürich Hospital, Gloriastrasse 31, 8091, Zurich, Switzerland. reinhard.dummer@usz.ch. · Medical University of Vienna, Vienna, Austria. · Amgen (Europe) GmBH, Zug, Switzerland. · Lausanne University Hospital, Lausanne, Switzerland. ·Cancer Immunol Immunother · Pubmed #28238174.

ABSTRACT: Talimogene laherparepvec is a first-in-class intralesional oncolytic immunotherapy. In a recent Phase III trial (OPTiM), talimogene laherparepvec significantly improved durable response rate compared with subcutaneous granulocyte-macrophage colony-stimulating factor (GM-CSF). Overall response rate was also higher in the talimogene laherparepvec arm, and the greatest efficacy was demonstrated in patients with earlier-stage (IIIB, IIIC, or IVM1a) melanoma. Talimogene laherparepvec was well tolerated, with the majority (89%) of adverse events being grade 1 or 2. Preclinical studies have shown that talimogene laherparepvec exerts antitumor activity by selectively replicating within and destroying cancer cells, and through the release of tumor-associated antigens and expression of GM-CSF, which facilitates a wider antitumor immune response. It is hypothesized that combining talimogene laherparepvec with a systemic immunotherapy may, by bringing together complementary mechanisms of action, further enhance the efficacy of both agents. Indeed, talimogene laherparepvec is currently being assessed in combination with immune checkpoint inhibitors, including ipilimumab and pembrolizumab, in trials for melanoma and other solid tumors. Early results in melanoma indicate that the combination of talimogene laherparepvec with ipilimumab or pembrolizumab has greater efficacy than either therapy alone, without additional safety concerns above those expected for each monotherapy. In this review, we discuss the latest results from trials assessing talimogene laherparepvec in combination with other immunotherapies, provide an overview of ongoing and upcoming combination trials, and suggest future directions for talimogene laherparepvec in combination therapy for solid tumors.

13 Review Critical aspects to achieve a high-quality melanoma clinic. 2017

Dummer, Reinhard / Ramelyte, Egle / Levesque, Mitch / Goldinger, Simone M / Braun, Ralph P. ·aDepartment of Dermatology, University Hospital of Zurich, Zurich, Switzerland bVilnius University, Centre of Dermatovenereology, Vilnius, Lithuania. ·Curr Opin Oncol · Pubmed #28027104.

ABSTRACT: PURPOSE OF REVIEW: With incidence of melanoma growing worldwide and new therapies prolonging the survival of patients with advanced disease, complex medical care is needed. RECENT FINDINGS: Best care of complicated melanoma cases is achieved in specialized referral centers. Aims to provide optimized melanoma therapy, best patient-reported treatment outcome, and successful clinical and translational research, necessitate a dedicated interdisciplinary team. SUMMARY: We report on critical aspects of the interaction between patients, medical care givers, clinical trial and biobanking teams, and emphasize the importance of interdisciplinary tumor boards. Specialized skin cancer nurses and local patient advocacy groups should be involved in patient care and could be the binding link between the patients and the treatment team.

14 Review Developments in targeted therapy in melanoma. 2017

Amann, V C / Ramelyte, E / Thurneysen, S / Pitocco, R / Bentele-Jaberg, N / Goldinger, S M / Dummer, R / Mangana, J. ·Department of Dermatology, University Hospital Zurich, Zurich, Switzerland; University Department of Medicine, Kantonsspital Aarau, Tellstrasse, 5001 Aarau, Switzerland. · Department of Dermatology, University Hospital Zurich, Zurich, Switzerland; Vilnius University, Centre of Dermatovenereology, Vilnius, Lithuania. · Department of Dermatology, University Hospital Zurich, Zurich, Switzerland. · Department of Dermatology, University of Rome Tor Vergata, Rome, Italy. · Department of Dermatology, University Hospital Zurich, Zurich, Switzerland. Electronic address: reinhard.dummer@usz.ch. ·Eur J Surg Oncol · Pubmed #27923592.

ABSTRACT: Melanomas are disease entities driven in part by the mitogen activated protein kinase (MAPK) pathway. The TCGA network recently defined four genetic subtypes based on the most prevalent significantly mutated genes, including mutant BRAF, mutant RAS (N/H/K), mutant NF1, and Triple wild-type melanoma (harboring none of the aforementioned mutations, but instead includes KIT, GNA and GNAQ mutations). The successful development of kinase inhibitors marked a milestone in the treatment of metastatic melanoma. Combination treatment with a BRAF- and MEK-inhibitor is the current standard of care for inoperable stage IIIC/IV BRAF-mutated melanoma. Recent data demonstrate excellent long-term outcome, especially in patients with normal baseline LDH levels, and confirm that there is a subset of BRAF inhibitor-naive patients who experience durable responses without progression on combination treatment. In the future, adding a third compound based on individual genetic alterations might further improve the outcome of targeted therapy.

15 Review The safety of anti PD-1 therapeutics for the treatment of melanoma. 2017

Ramelyte, Egle / Schindler, Sabrina A / Dummer, Reinhard. ·a Department of Dermatology , University Hospital Zurich , Zurich , Switzerland. · b Centre of Dermatovenereology , Vilnius University Hospital Santariskiu klinikos , Vilnius , Lithuania. ·Expert Opin Drug Saf · Pubmed #27737598.

ABSTRACT: INTRODUCTION: The introduction of immunotherapies into clinical practice has substantially improved the prognosis of metastatic melanoma patients as well as patients suffering from other cancers. The two FDA-approved checkpoint inhibitors against PD-1 (nivolumab and pembrolizumab) have been shown to significantly improve patient survival while being less toxic than previous treatment options. Areas covered: The current scientific literature on safety and adverse events (AEs) related to anti-PD-1 therapies has been investigated with special attention to case reports and to the latest results announced at the major clinical cancer and melanoma meetings, including ASCO (American Society of Clinical Oncology), ESMO (European Society of medical Oncology) and EADO (European Association of Dermato-Oncology) annual meetings. Expert opinion: Even though anti-PD-1 therapies are better tolerated than conventional chemo- or other immune-therapies, they still induce a plethora of AEs. Given the mechanism of action, it is supposed that most if not all of them are immune related. Fortunately, the majority are mild and manageable. However, due to the increase in patients' life expectancy, there is a substantial need to understand and prevent severe cutaneous, pulmonary, neurological and other AEs which have major impact on the quality of life. The safety profile after long term use of these medications is still unclear. In addition, non-steroid based immune interventions to control autoimmunity are still to be developed.

16 Review The updated Swiss guidelines 2016 for the treatment and follow-up of cutaneous melanoma. 2016

Dummer, Reinhard / Siano, Marco / Hunger, Robert E / Lindenblatt, Nicole / Braun, Ralph / Michielin, Oliver / Mihic-Probst, Daniela / von Moos, Roger / Najafi, Yousef / Guckenberger, Merlin / Arnold, Andreas. ·Skin Cancer Centre, Dept. of Dermatology, University Hospital of Zurich, Switzerland. · Dept. of Oncology, Kantonalspital St. Gallen, Switzerland. · Skin Cancer Centre, Dept. of Dermatology, University of Bern, Inselspital, Bern, Switzerland. · Division of Plastic Surgery and Hand Surgery, University Hospital of Zurich, Switzerland. · Dept. of Oncology, University Hospital of Lausanne, Switzerland. · Dept. of surgical Pathology, University Hospital of Zurich, Switzerland. · Dept. of Oncology, Kantonalspital Chur, Switzerland. · Dept. Radiation Oncology, University Hospital of Zurich, Switzerland. · Dept. of Dermatology, University Hospital of Basel, Switzerland. ·Swiss Med Wkly · Pubmed #26901103.

ABSTRACT: Cutaneous melanoma is the most deadly cutaneous neoplasm. In order to guide treatment decisions and follow-up of melanoma patients, guidelines for the management of melanoma in Switzerland were inaugurated in 2001 and revised in 2006 and 2016. Recent data on surgical and medical treatments from randomised trials necessitated modification of the treatment and follow-up recommendations.

17 Review Integrating first-line treatment options into clinical practice: what's new in advanced melanoma? 2015

Dummer, Reinhard / Schadendorf, Dirk / Ascierto, Paolo A / Larkin, James / Lebbé, Celeste / Hauschild, Axel. ·aDepartment of Dermatology, University Hospital Zürich, Zürich, Switzerland bDepartment of Dermatology, University Hospital Essen, Essen cDepartment of Dermatology, University Hospital Schleswig-Holstein, Kiel, Germany dIstituto Nazionale Tumori Fondazione 'G. Pascale', Naples, Italy eRoyal Marsden NHS Foundation Trust, London, UK fAPHP Oncodermatology Unit, University Paris 7 Diderot U976, Paris, France. ·Melanoma Res · Pubmed #26426764.

ABSTRACT: Melanoma remains a serious form of skin cancer in Europe and worldwide. Localized, early-stage melanomas can usually be treated with surgical excision. However, the prognosis is poorer for patients with advanced disease. Before 2011, treatment for advanced melanoma included palliative surgery and/or radiotherapy, and chemotherapy with or without immunotherapy, such as interleukin-2. As none of these treatments had shown survival benefits in patients with advanced melanoma, European guidelines had recommended that patients be entered into clinical trials. The lack of approved first-line options and varying access to clinical trials meant that European clinicians relied on experimental regimens and chemotherapy-based treatments when no other options were available. Since 2011, ipilimumab, an immuno-oncology therapy, and vemurafenib and dabrafenib, targeted agents that inhibit mutant BRAF, have been approved by the European Medicines Agency for the treatment of advanced melanoma. More recently, the MEK inhibitor, trametinib, received European marketing authorization for use in patients with BRAF mutation-positive advanced melanoma. In 2014, the anti-PD-1 antibody nivolumab was approved as a first-line therapy in Japan. Whereas nivolumab and another anti-PD-1 antibody, pembrolizumab, were approved as second-line therapies in the USA, their recent approval in Europe are for first-line use based on new clinical trial data in this setting. Together these agents are changing clinical practice and making therapeutic decisions more complex. Here, we discuss current and emerging therapeutic options for the first-line treatment of advanced melanoma, and how these therapies can be optimized to provide the best possible outcomes for patients.

18 Review Achievements and challenges of molecular targeted therapy in melanoma. 2015

Sullivan, Ryan / LoRusso, Patricia / Boerner, Scott / Dummer, Reinhard. ·From the Massachusetts General Hospital Cancer Center, Boston, MA; Yale Cancer Center, New Haven, CT; Yale University, New Haven, CT; University Hospital of Zurich, Zurich, Switzerland. ·Am Soc Clin Oncol Educ Book · Pubmed #25993155.

ABSTRACT: The treatment of melanoma has been revolutionized over the past decade with the development of effective molecular and immune targeted therapies. The great majority of patients with melanoma have mutations in oncogenes that predominantly drive signaling through the mitogen activated protein kinase (MAPK) pathway. Analytic tools have been developed that can effectively stratify patients into molecular subsets based on the identification of mutations in oncogenes and/or tumor suppressor genes that drive the MAPK pathway. At the same time, potent and selective inhibitors of mediators of the MAPK pathway such as RAF, MEK, and ERK have become available. The most dramatic example is the development of single-agent inhibitors of BRAF (vemurafenib, dabrafenib, encorafenib) and MEK (trametinib, cobimetinib, binimetinib) for patients with metastatic BRAFV600-mutant melanoma, a subset that represents 40% to 50% of patients with metastatic melanoma. More recently, the elucidation of mechanisms underlying resistance to single-agent BRAF inhibitor therapy led to a second generation of trials that demonstrated the superiority of BRAF inhibitor/MEK inhibitor combinations (dabrafenib/trametinib; vemurafenib/cobimetinib) compared to single-agent BRAF inhibitors. Moving beyond BRAFV600 targeting, a number of other molecular subsets--such as mutations in MEK, NRAS, and non-V600 BRAF and loss of function of the tumor suppressor neurofibromatosis 1 (NF1)--are predicted to respond to MAPK pathway targeting by single-agent pan-RAF, MEK, or ERK inhibitors. As these strategies are being tested in clinical trials, preclinical and early clinical trial data are now emerging about which combinatorial approaches might be best for these patients.

19 Review Curing advanced melanoma by 2025. 2015

Dummer, Reinhard / Goldinger, Simone M / Paulitschke, Verena / Levesque, Mitchell P. ·Department of Dermatology, University Hospital Zurich, Zurich, Switzerland. ·Curr Opin Oncol · Pubmed #25646843.

ABSTRACT: PURPOSE OF REVIEW: To outline the most urgent challenges in the management of advanced melanoma. RECENT FINDINGS: Considerable progress in targeted and immunotherapy of advanced melanoma has opened a perspective for a cure if all molecular and medical information is integrated in a rational precision treatment algorithm. SUMMARY: Bioinformatics and system biology approaches will be needed to deal with omics databases. The support of patient advocacy groups may help to increase the acceptance of large scale, routine biobanking.

20 Review Treatment algorithms in stage IV melanoma. 2015

Espinosa, Enrique / Grob, Jean-Jacques / Dummer, Reinhard / Rutkowski, Piotr / Robert, Caroline / Gogas, Helen / Kefford, Richard / Eggermont, Alexander M M / Martin Algarra, Salvador / Hauschild, Axel / Schadendorf, Dirk. ·1Service of Oncology, Hospital La Paz, Madrid, Spain · 2Department of Dermatology, Hopital Ste Marguerite, Marseille, France · 3Department of Dermatology, University Hospital of Zurich, Zurich, Switzerland · 4Department of Sarcoma and Melanoma, M. Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw, Poland · 5Department of Dermatology (CR), and General Director (AE), Institute Gustave Roussy, Villejuif Cedex, France · 6First Department of Medicine, University of Athens Medical School, Athens, Greece · 7Department of Oncology, Westmead Hospital and Melanoma Institute Australia, University of Sydney, Sydney, Australia · 8Service of Oncology, Clinica Universitaria de Navarra, Pamplona, Spain · 9Department of Dermatology, University of Kiel, Kiel, Germany · and 10Department of Dermatology, University Hospital Essen, Essen, Germany. ·Am J Ther · Pubmed #24413374.

ABSTRACT: The molecular classification of melanoma and the advent of new drugs are changing the paradigm of therapy for advanced melanoma. A review of the recent key studies was performed, followed by a discussion in an expert forum. The aim of this review was to generate a therapeutic algorithm for stage IV melanoma. Tumor genotyping for BRAF and/or KIT should be performed before selection of therapy. For most BRAF-mutated melanoma patients and particularly those with a high tumor load, vemurafenib or other BRAF inhibitors such as dabrafenib are the treatment of choice. KIT inhibitors can be effective in KIT-mutant tumors, especially in those patients with mutations at exons 11 and 13. Ipilimumab is a good option for patients with nontargetable or nondetected mutations and those who progress under therapy with vemurafenib or a KIT inhibitor. There is still a role for conventional chemotherapy either as first-line treatment in BRAF wild-type patients or as salvage therapy in second or third line, or after other treatment modalities. Participation in clinical trials is strongly encouraged, either in first or in subsequent lines. New therapeutic options for advanced melanoma are guided by tumor genotyping. The current therapeutic algorithm includes kinase inhibitors, anti-CTLA4 therapy, immunotherapy, and chemotherapy, depending on the tumor genotype and response to previous treatments. Participation in clinical trials should always be encouraged because the treatment goal is long-term survival and potential cure in a subset of patients.

21 Review Melanoma immunotherapy: historical precedents, recent successes and future prospects. 2013

Raaijmakers, Marieke I G / Rozati, Sima / Goldinger, Simone M / Widmer, Daniel S / Dummer, Reinhard / Levesque, Mitchell P. ·Department of Dermatology, University Hospital of Zurich, Gloriastrasse 31, CH-8091 Zurich, Switzerland. ·Immunotherapy · Pubmed #23413908.

ABSTRACT: The idea of cancer immunotherapy has been around for more than a century; however, the first immunotherapeutic ipilimumab, an anti-CTLA-4 antibody, has only recently been approved by the US FDA for melanoma. With an increasing understanding of the immune response, it is expected that more therapies will follow. This review aims to provide a general overview of immunotherapy in melanoma. We first explain the development of cancer immunotherapy more than a century ago and the general opinions about it over time. This is followed by a general overview of the immune reaction in order to give insight into the possible targets for therapy. Finally, we will discuss the current therapies for melanoma, their shortcomings and why it is important to develop patient stratification criteria. We conclude with an overview of recent discoveries and possible future therapies.

22 Review [Therapeutic approaches in Melanoma - a paradigm for personalized medicine]. 2012

Dummer, R / Goldinger, S / Rinderknecht, J / Eggmann, N / Felderer, L / Braun, R / French, L E. ·Dermatologische Klinik, Universitätsspital Zürich. reinhard.dummer@usz.ch ·Praxis (Bern 1994) · Pubmed #22811327.

ABSTRACT: Progress in molecular biology has facilitated a new classification for melanoma. Melanomas today are considered as a heterogeneous group of tumors. The different subtypes are characterized by specific genetic alterations, including mutations in kinase, such as B-RAF or c-kit. New medications like vemurafenib have been developed and are available for the systemic therapy of advanced melanomas in subpopulations identified by mutation tests. In addition, interferon therapy holds the highest promises to dates in subpopulations of patients characterized by microscopic lymph node involvement and ulceration of the primary tumor. These developments are the first steps resulting in a personalized treatment approach for individuals affected by melanoma.

23 Review Management of pegylated interferon alpha toxicity in adjuvant therapy of melanoma. 2012

Daud, Adil / Soon, Christopher / Dummer, Reinhard / Eggermont, Alexander M M / Hwu, Wen-Jen / Grob, Jean Jacques / Garbe, Claus / Hauschild, Axel. ·University of California, San Francisco, Melanoma Program, San Francisco 1600 Divisadero St, Rm A741, Box 1770, San Francisco, CA 94115, USA. adaud@medicine.ucsf.edu ·Expert Opin Biol Ther · Pubmed #22694288.

ABSTRACT: INTRODUCTION: Both native IFNα2b and pegylated IFNα2b (PegIFNα2b) are approved for the adjuvant treatment of high-risk melanoma. AREAS COVERED: This review compares the toxicity profiles of high-dose IFNα2b (HDI) and PegIFNα2b, and provides recommendations on the management of common PegIFNα2b-related toxicities, based on available clinical data and published literature. EXPERT OPINION: The toxicity profile of PegIFNα2b at the approved dose (6 μg/kg/week for 8 weeks then 3 μg/kg/week for up to 5 years) is qualitatively similar to HDI in melanoma. The most common adverse events (AEs) are fatigue, anorexia, hepatotoxicity, flu-like symptoms, injection site reactions and depression. However, fatigue and flu-like symptoms appear less severe with PegIFNα2b, and toxicity seems to occur earlier, whereas with HDI toxicity may increase with time. Most AEs can be managed effectively by dose modification and aggressive symptom control. Dosing to tolerance using a three-step dose reduction schedule to maintain an ECOG performance status of 0 - 1 may enable patients experiencing toxicity to remain on treatment; this can be applied readily in clinical practice. PegIFNα2b is therefore a valuable alternative option for adjuvant treatment in melanoma, with a toxicity profile similar to that of HDI overall but a more convenient administration schedule.

24 Review Sorafenib in melanoma. 2012

Mangana, Joanna / Levesque, Mitchell P / Karpova, Maria B / Dummer, Reinhard. ·University Hospital of Zurich, Department of Dermatology, Gloriastrasse 31, Zurich, 8091, Switzerland. ·Expert Opin Investig Drugs · Pubmed #22394203.

ABSTRACT: INTRODUCTION: Sorafenib is an orally available multi-kinase inhibitor that inhibits tumor proliferation by targeting multiple kinases including the vascular endothelial growth factor receptors VEGFR1, VEGFR2, VEGFR3 and the platelet-derived growth factor receptor PDGFR, and it targets tumor progression by inhibiting FLT3, C-Kit and BRAF. Since BRAF mutations are frequent in melanoma, sorafenib was investigated in various Phase I, II and III clinical trials. The drug is well tolerated with mild to moderate adverse effects, which are mostly limited to cutaneous toxicity, diarrhea and fatigue. AREAS COVERED: Systematic literature review of the randomized trials using PubMed was performed. Original articles were reviewed and citations from those were also considered. Additionally, clinical trial databases were examined to identify and summarize ongoing trials of sorafenib in melanoma patients. EXPERT OPINION: Sorafenib as a monotherapy or in combination with chemotherapy is of limited use. Combining it with dacarbazine doubled the response rate and the progression-free survival in metastatic melanoma patients. Unfortunately, these results have never been evaluated in large randomized Phase III clinical trials. According to the trials conducted so far a subpopulation of patients experience substantial benefit, therefore it is essential to identify biomarkers to select the subgroups of patients that are more likely to respond to sorafenib. Furthermore, other less frequent subtypes such as mucosal or ocular melanoma still constitute promising targets; academic institutions are currently launching investigator-initiated trials in these indications.

25 Review Resistance patterns with tyrosine kinase inhibitors in melanoma: new insights. 2012

Dummer, Reinhard / Flaherty, Keith T. ·Department of Dermatology, University Hospital Zurich, Zurich, Switzerland. reinhard.dummer@usz.ch ·Curr Opin Oncol · Pubmed #22316627.

ABSTRACT: PURPOSE OF REVIEW: After years of therapeutic approaches with limited effects in metastatic melanoma, new inhibitors of serine-threonine and tyrosine kinases have demonstrated impressive clinical efficacy and improved survival. RECENT FINDINGS: This review explains the molecular background for the development of specific kinase inhibitors and briefly summarizes their clinical impact on advanced melanoma. SUMMARY: Despite robust early clinical efficacy, the antiproliferative effect of these kinase inhibitors is limited. The resistance mechanisms are explored currently and will help to identify new targets for melanoma therapy.