Browsing by Author "Heppt, Markus"

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Early Exanthema Upon Vemurafenib Plus Cobimetinib Is Associated With a Favorable Treatment Outcome in Metastatic Melanoma: A Retrospective Multicenter DeCOG Study
(2021)
Kähler, Katharina C.
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Gutzmer, Ralf
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Meier, Friedegrund
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Zimmer, Lisa
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Heppt, Markus
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Gesierich, Anja
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Thoms, Kai-Martin
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Utikal, Jochen
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Hassel, Jessica C.
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Ugurel, Selma
Background The combination of BRAF and MEK inhibitors has become standard of care in the treatment of metastatic BRAF V600-mutated melanoma. Clinical factors for an early prediction of tumor response are rare. The present study investigated the association between the development of an early exanthema induced by vemurafenib or vemurafenib plus cobimetinib and therapy outcome. Methods This multicenter retrospective study included patients with BRAF V600-mutated irresectable AJCC-v8 stage IIIC/D to IV metastatic melanoma who received treatment with vemurafenib (VEM) or vemurafenib plus cobimetinib (COBIVEM). The development of an early exanthema within six weeks after therapy start and its grading according to CTCAEv4.0 criteria was correlated to therapy outcome in terms of best overall response, progression-free (PFS), and overall survival (OS). Results A total of 422 patients from 16 centers were included (VEM, n=299; COBIVEM, n=123). 20.4% of VEM and 43.1% of COBIVEM patients developed an early exanthema. In the VEM cohort, objective responders (CR/PR) more frequently presented with an early exanthema than non-responders (SD/PD); 59.0% versus 38.7%; p=0.0027. However, median PFS and OS did not differ between VEM patients with or without an early exanthema (PFS, 6.9 versus 6.0 months, p=0.65; OS, 11.0 versus 12.4 months, p=0.69). In the COBIVEM cohort, 66.0% of objective responders had an early exanthema compared to 54.3% of non-responders (p=0.031). Median survival times were significantly longer for patients who developed an early exanthema compared to patients who did not (PFS, 9.7 versus 5.6 months, p=0.013; OS, not reached versus 11.6 months, p=0.0061). COBIVEM patients with a mild early exanthema (CTCAEv4.0 grade 1-2) had a superior survival outcome as compared to COBIVEM patients with a severe (CTCAEv4.0 grade 3-4) or non early exanthema, respectively (p=0.047). This might be caused by the fact that 23.6% of patients with severe exanthema underwent a dose reduction or discontinuation of COBIVEM compared to only 8.9% of patients with mild exanthema. Conclusions The development of an early exanthema within 6 weeks after treatment start indicates a favorable therapy outcome upon vemurafenib plus cobimetinib. Patients presenting with an early exanthema should therefore be treated with adequate supportive measures to provide that patients can stay on treatment.
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Immune Checkpoint Blockade for Metastatic Uveal Melanoma: Patterns of Response and Survival According to the Presence of Hepatic and Extrahepatic Metastasis
(MDPI, 2021)
Koch, Elias
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Petzold, Anne
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Wessely, Anja
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Dippel, Edgar
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Gesierich, Anja
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Gutzmer, Ralf
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Hassel, Jessica
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Haferkamp, Sebastian
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Hohberger, Bettina
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Heppt, Markus
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Thoms, Kai-Martin
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Kähler, Katharina
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Knorr, Harald
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Kreuzberg, Nicole
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Leiter, Ulrike
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Loquai, Carmen
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Meier, Friedegund
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Meissner, Markus
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Mohr, Peter
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Pföhler, Claudia
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Rahimi, Farnaz
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Schadendorf, Dirk
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Schell, Beatrice
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Schlaak, Max
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Terheyden, Patrick
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Schuler-Thurner, Beatrice
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Ugurel, Selma
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Ulrich, Jens
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Utikal, Jochen
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Weichenthal, Michael
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Ziller, Fabian
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Berking, Carola
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Koch, Elias; Department of Dermatology, Universitätsklinikum Erlangen, Friedrich-Alexander-University Erlangen-Nürnberg (FAU), 91054 Erlangen, Germany, elias.koch@uk-erlangen.de Comprehensive Cancer Center Erlangen-European Metropolitan Area of Nuremberg (CCC ER-EMN), 91054 Erlangen, Germany, elias.koch@uk-erlangen.de
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Petzold, Anne; Department of Dermatology, Universitätsklinikum Erlangen, Friedrich-Alexander-University Erlangen-Nürnberg (FAU), 91054 Erlangen, Germany, Anne.Petzold@uk-erlangen.de Comprehensive Cancer Center Erlangen-European Metropolitan Area of Nuremberg (CCC ER-EMN), 91054 Erlangen, Germany, Anne.Petzold@uk-erlangen.de
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Wessely, Anja; Department of Dermatology, Universitätsklinikum Erlangen, Friedrich-Alexander-University Erlangen-Nürnberg (FAU), 91054 Erlangen, Germany, Anja.Wessely@uk-erlangen.de Comprehensive Cancer Center Erlangen-European Metropolitan Area of Nuremberg (CCC ER-EMN), 91054 Erlangen, Germany, Anja.Wessely@uk-erlangen.de
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Dippel, Edgar; Department of Dermatology, Ludwigshafen Medical Center, 67059 Ludwigshafen, Germany, dippele@klilu.de
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Gesierich, Anja; Department of Dermatology, University Hospital Würzburg, 97080 Würzburg, Germany, gesierich_a@ukw.de
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Gutzmer, Ralf; Skin Cancer Center Minden, Department of Dermatology, Mühlenkreiskliniken AöR, Ruhr University Bochum Campus Minden, 32423 Minden, Germany, Ralf.Gutzmer@ruhr-uni-bochum.de
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Hassel, Jessica; Skin Cancer Center, Department of Dermatology and National Center for Tumor Diseases (NCT), University Hospital Heidelberg, 69120 Heidelberg, Germany, Jessica.Hassel@med.uni-heidelberg.de
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Haferkamp, Sebastian; Department of Dermatology, University Hospital Regensburg, 93053 Regensburg, Germany, sebastian.haferkamp@ukr.de
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Hohberger, Bettina; Department of Ophthalmology, Universitätsklinikum Erlangen, Friedrich-Alexander-University Erlangen-Nürnberg (FAU), 91054 Erlangen, Germany, Bettina.Hohberger@uk-erlangen.de
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Kähler, Katharina; Department of Dermatology, University Hospital Schleswig-Holstein, Campus Kiel, 24105 Kiel, Germany, kckaehler@yahoo.de
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Knorr, Harald; Department of Ophthalmology, Universitätsklinikum Erlangen, Friedrich-Alexander-University Erlangen-Nürnberg (FAU), 91054 Erlangen, Germany, Harald.Knorr@uk-erlangen.de
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Kreuzberg, Nicole; Department of Dermatology and Venereology, Skin Cancer Center at the Center of Integrated Oncology (CIO) Köln Bonn, University Hospital of Cologne, 50937 Cologne, Germany, nicole.kreuzberg@uk-koeln.de
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Leiter, Ulrike; Department of Dermatology, Center for Dermatooncology, University Hospital Tübingen, 72056 Tübingen, Germany, Ulrike.Leiter@med.uni-tuebingen.de
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Loquai, Carmen; Department of Dermatology, University Medical Center Mainz, 55131 Mainz, Germany, carmen.loquai@unimedizin-mainz.de
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Meier, Friedegund; Skin Cancer Center at the University Cancer Centre Dresden and National Center for Tumor Diseases & Department of Dermatology, University Hospital Carl Gustav Carus, 01307 Dresden, Germany, Friedegund.Meier@uniklinikum-dresden.de
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Meissner, Markus; Department of Dermatology, Venereology and Allergology, Goethe University, 60590 Frankfurt am Main, Germany, markus.meissner@kgu.de
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Mohr, Peter; Department of Dermatology, Elbeklinikum, 21614 Buxtehude, Germany, peter.mohr@elbekliniken.de
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Pföhler, Claudia; Department of Dermatology, Saarland University Medical School, 66421 Homburg/Saar, Germany, claudia.pfoehler@uks.eu
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Rahimi, Farnaz; Department of Dermatology and Allergy, Munich University Hospital (LMU), 81377 Munich, Germany, Farnaz.Rahimi@med.uni-muenchen.de
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Schadendorf, Dirk; Department of Dermatology, University Hospital Essen, University Duisburg-Essen, 45147 Essen, Germany, Dirk.Schadendorf@uk-essen.de German Cancer Consortium, Partner Site Essen, 45147 Essen, Germany, Dirk.Schadendorf@uk-essen.de
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Schell, Beatrice; Department of Dermatology, SRH Wald-Klinikum Gera, 07548 Gera, Germany, Beatrice.Schell@srh.de
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Schlaak, Max; Department of Dermatology, Venerology and Allergology, Charité—Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, 10117 Berlin, Germany, max.schlaak@charite.de
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Terheyden, Patrick; Department of Dermatology, University of Lübeck, 23562 Lübeck, Germany, patrick.terheyden@uksh.de
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Thoms, Kai-Martin; Department of Dermatology, University Medical Center Goettingen, 37075 Goettingen, Germany, kai.thoms@med.uni-goettingen.de
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Schuler-Thurner, Beatrice; Department of Dermatology, Universitätsklinikum Erlangen, Friedrich-Alexander-University Erlangen-Nürnberg (FAU), 91054 Erlangen, Germany, Beatrice.Schuler-Thurner@uk-erlangen.de Comprehensive Cancer Center Erlangen-European Metropolitan Area of Nuremberg (CCC ER-EMN), 91054 Erlangen, Germany, Beatrice.Schuler-Thurner@uk-erlangen.de
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Ugurel, Selma; Department of Dermatology, University Hospital Essen, University Duisburg-Essen, 45147 Essen, Germany, Selma.Ugurel@uk-essen.de
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Ulrich, Jens; Department of Dermatology, Harzklinikum Dorothea Christiane Erxleben, 06484 Quedlinburg, Germany, jens.ulrich@harzklinikum.com
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Utikal, Jochen; Skin Cancer Unit, German Cancer Research Center (DKFZ), 68167 Heidelberg, Germany, Jochen.Utikal@umm.de Department of Dermatology, Venereology and Allergology, University Medical Center Mannheim, Ruprecht-Karl University of Heidelberg, 68167 Mannheim, Germany, Jochen.Utikal@umm.de
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Weichenthal, Michael; Department of Dermatology, University Hospital Schleswig-Holstein, Campus Kiel, 24105 Kiel, Germany, mweichenthal@dermatology.uni-kiel.de
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Ziller, Fabian; Department of Dermatology, DRK Krankenhaus Rabenstein, 09117 Chemnitz, Germany, Ziller.Fabian@drk-khs.de
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Berking, Carola; Department of Dermatology, Universitätsklinikum Erlangen, Friedrich-Alexander-University Erlangen-Nürnberg (FAU), 91054 Erlangen, Germany, Carola.Berking@uk-erlangen.de Comprehensive Cancer Center Erlangen-European Metropolitan Area of Nuremberg (CCC ER-EMN), 91054 Erlangen, Germany, Carola.Berking@uk-erlangen.de
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Heppt, Markus; Department of Dermatology, Universitätsklinikum Erlangen, Friedrich-Alexander-University Erlangen-Nürnberg (FAU), 91054 Erlangen, Germany, Markus.Heppt@uk-erlangen.de Comprehensive Cancer Center Erlangen-European Metropolitan Area of Nuremberg (CCC ER-EMN), 91054 Erlangen, Germany, Markus.Heppt@uk-erlangen.de
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on behalf of the German Dermatologic Cooperative Oncology Group (DeCOG, Committee Ocular Melanoma)
Background: Since there is no standardized and effective treatment for advanced uveal melanoma (UM), the prognosis is dismal once metastases develop. Due to the availability of immune checkpoint blockade (ICB) in the real-world setting, the prognosis of metastatic UM has improved. However, it is unclear how the presence of hepatic and extrahepatic metastasis impacts the response and survival after ICB. Methods: A total of 178 patients with metastatic UM treated with ICB were included in this analysis. Patients were recruited from German skin cancer centers and the German national skin cancer registry (ADOReg). To investigate the impact of hepatic metastasis, two cohorts were compared: patients with liver metastasis only (cohort A, n = 55) versus those with both liver and extra-hepatic metastasis (cohort B, n = 123). Data were analyzed in both cohorts for response to treatment, progression-free survival (PFS), and overall survival (OS). The survival and progression probabilities were calculated with the Kaplan–Meier method. Log-rank tests, χ2 tests, and t-tests were performed to detect significant differences between both cohorts. Results: The median OS of the overall population was 16 months (95% CI 13.4–23.7) and the median PFS, 2.8 months (95% CI 2.5–3.0). The median OS was longer in cohort B than in cohort A (18.2 vs. 6.1 months; p = 0.071). The best objective response rate to dual ICB was 13.8% and to anti-PD-1 monotherapy 8.9% in the entire population. Patients with liver metastases only had a lower response to dual ICB, yet without significance (cohort A 8.7% vs. cohort B 16.7%; p = 0.45). Adverse events (AE) occurred in 41.6%. Severe AE were observed in 26.3% and evenly distributed between both cohorts. Conclusion: The survival of this large cohort of patients with advanced UM was more favorable than reported in previous benchmark studies. Patients with both hepatic and extrahepatic metastasis showed more favorable survival and higher response to dual ICB than those with hepatic metastasis only.