Real-world outcomes using PD-1 antibodies and BRAF plus MEK inhibitors for adjuvant melanoma treatment from 39 skin cancer centers in Germany, Austria and Switzerland

Schumann K, Mauch C, Klespe KC, Loquai C, Nikfarjam U, Schlaak M, Akcetin L, Koelblinger P, Hoellwerth M, Meissner M, Mengi G, Braun AD, Mengoni M, Dummer R, Mangana J, Sindrilaru MA, Radmann D, Hafner C, Freund J, Rappersberger K, Weihsengruber F, Meiss F, Reinhardt L, Meier F, Rainer B, Richtig E, Ressler JM, Hoeller C, Eigentler T, Amaral T, Peitsch WK, Hillen U, Harth W, Ziller F, Schatton K, Gambichler T, Susok L, Maul LV, Laubli H, Debus D, Weishaupt C, Boerger S, Sievers K, Haferkamp S, Zenderowski V, Nguyen VA, Wanner M, Gutzmer R, Terheyden P, Kaehler K, Emmert S, Thiem A, Sachse M, Gercken-Riedel S, Kaune KM, Thoms KM, Heinzerling L, Heppt M, Tratzmiller S, Hoetzenecker W, Oellinger A, Steiner A, Peinhaupt T, Podda M, Schmid S, Wollina U, Biedermann T, Posch C (2022)

Publication Type: Journal article

Publication year: 2022

Journal

DOI: 10.1111/jdv.18779

Abstract

BackgroundProgrammed death-1 (PD-1) antibodies and BRAF + MEK inhibitors are widely used for adjuvant therapy of fully resected high-risk melanoma. Little is known about treatment efficacy outside of phase III trials. This real-world study reports on clinical outcomes of modern adjuvant melanoma treatment in specialized skin cancer centers in Germany, Austria and Switzerland. MethodsMulticenter, retrospective study investigating stage III-IV melanoma patients receiving adjuvant nivolumab (NIV), pembrolizumab (PEM) or dabrafenib + trametinib (D + T) between 1/2017 and 10/2021. The primary endpoint was 12-month recurrence-free survival (RFS). Further analyses included descriptive and correlative statistics, and a multivariate linear-regression machine learning model to assess the risk of early melanoma recurrence. ResultsIn total, 1198 patients from 39 skin cancer centers from Germany, Austria and Switzerland were analysed. The vast majority received anti PD-1 therapies (n = 1003). Twelve-month RFS for anti PD-1 and BRAF + MEK inhibitor-treated patients were 78.1% and 86.5%, respectively (hazard ratio [HR] 1.998 [95% CI 1.335-2.991]; p = 0.001). There was no statistically significant difference in overall survival (OS) in anti PD-1 (95.8%) and BRAF + MEK inhibitor (96.9%) treated patients (p > 0.05) during the median follow-up of 17 months. Data indicates that anti PD-1 treated patients who develop immune-related adverse events (irAEs) have lower recurrence rates compared to patients with no irAEs (HR 0.578 [95% CI 0.443-0.754], p = 0.001). BRAF mutation status did not affect overall efficacy of anti PD-1 treatment (p > 0.05). In both, anti PD-1 and BRAF + MEK inhibitor treated cohorts, data did not show any difference in 12-month RFS and 12-month OS comparing patients receiving total lymph node dissection (TLND) versus sentinel lymph node biopsy only (p > 0.05). The recurrence prediction model reached high specificity but only low sensitivity with an AUC = 0.65. No new safety signals were detected. Overall, recorded numbers and severity of adverse events were lower than reported in pivotal phase III trials. ConclusionsDespite recent advances in adjuvant melanoma treatment, early recurrence remains a significant clinical challenge. This study shows that TLND does not reduce the risk of early melanoma recurrence and should only be considered in selected patients. Data further highlight that variables collected during clinical routine are unlikely to allow for a clinically relevant prediction of individual recurrence risk.

Authors with CRIS profile

Involved external institutions

Technische Universität München (TUM) Germany (DE) Universitätsklinikum Köln Germany (DE) Johannes Gutenberg-Universität Mainz (JGU) Germany (DE) Charité - Universitätsmedizin Berlin Germany (DE) Ludwig-Maximilians-Universität (LMU) Germany (DE) Paracelsus Medizinische Privatuniversität Austria (AT) Universitätsklinikum Frankfurt am Main (KGU) Germany (DE) Universitätsklinikum Magdeburg A.ö.R. Germany (DE) Universitätsspital Zürich (USZ) Switzerland (CH) Universitätsklinikum Ulm Germany (DE) Karl Landsteiner Privatuniversität für Gesundheitswissenschaften GmbH Austria (AT) Albert-Ludwigs-Universität Freiburg Germany (DE) Universitätsklinikum Carl Gustav Carus Dresden Germany (DE) Medizinische Universität Wien Austria (AT) Universitätsklinikum Tübingen Germany (DE) Vivantes - Netzwerk für Gesundheit GmbH Germany (DE) Vivantes Klinikum Berlin Spandau Germany (DE) DRK Krankenhaus Chemnitz-Rabenstein Germany (DE) Universitätsklinikum Düsseldorf Germany (DE) Ruhr-Universität Bochum (RUB) Germany (DE) Universitätsspital Basel Switzerland (CH) Universitätsklinikum Münster Germany (DE) Universitätsklinikum Regensburg Germany (DE) Medizinische Universität Innsbruck Austria (AT) Mühlenkreiskliniken Germany (DE) Universitätsklinikum Schleswig-Holstein (UKSH) Germany (DE) Universitätsmedizin Rostock Germany (DE) Klinikum Bremerhaven-Reinkenheide Germany (DE) Klinikum Bremen-Mitte Germany (DE) Georg-August-Universität Göttingen Germany (DE) Städtisches Klinikum Karlsruhe Germany (DE) Johannes Kepler Universität (JKU) Linz Austria (AT) Krankenhaus Hietzing mit Neurologischem Zentrum Rosenhügel Austria (AT) Klinikum Darmstadt Germany (DE) Krankenhaus Dresden-Friedrichstadt, Städtisches Klinikum Germany (DE)

How to cite

APA:

Schumann, K., Mauch, C., Klespe, K.-C., Loquai, C., Nikfarjam, U., Schlaak, M.,... Posch, C. (2022). Real-world outcomes using PD-1 antibodies and BRAF plus MEK inhibitors for adjuvant melanoma treatment from 39 skin cancer centers in Germany, Austria and Switzerland. Journal of the European Academy of Dermatology and Venereology. https://doi.org/10.1111/jdv.18779

MLA:

Schumann, Katharina, et al. "Real-world outcomes using PD-1 antibodies and BRAF plus MEK inhibitors for adjuvant melanoma treatment from 39 skin cancer centers in Germany, Austria and Switzerland." Journal of the European Academy of Dermatology and Venereology (2022).

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