Schumann, Katharina and Mauch, Cornelia and Klespe, Kai-Christian and Loquai, Carmen and Nikfarjam, Ulrike and Schlaak, Max and Akcetin, Larissa and Koelblinger, Peter and Hoellwerth, Magdalena and Meissner, Markus and Mengi, Guelcin and Braun, Andreas Dominik and Mengoni, Miriam and Dummer, Reinhard and Mangana, Joanna and Sindrilaru, Mihaela-Anca and Radmann, Dan and Hafner, Christine and Freund, Johann and Rappersberger, Klemens and Weihsengruber, Felix and Meiss, Frank and Reinhardt, Lydia and Meier, Friedegund and Rainer, Barbara and Richtig, Erika and Ressler, Julia Maria and Hoeller, Christoph and Eigentler, Thomas and Amaral, Teresa and Peitsch, Wiebke K. and Hillen, Uwe and Harth, Wolfgang and Ziller, Fabian and Schatton, Kerstin and Gambichler, Thilo and Susok, Laura and Maul, Lara Valeska and Laubli, Heinz and Debus, Dirk and Weishaupt, Carsten and Boerger, Sevil and Sievers, Katharina and Haferkamp, Sebastian and Zenderowski, Veronika and Nguyen, Van Anh and Wanner, Marina and Gutzmer, Ralf and Terheyden, Patrick and Kaehler, Katharina and Emmert, Steffen and Thiem, Alexander and Sachse, Michael and Gercken-Riedel, Silke and Kaune, Kjell Matthias and Thoms, Kai-Martin and Heinzerling, Lucie and Heppt, Markus Vincent and Tratzmiller, Sabine and Hoetzenecker, Wolfram and Oellinger, Angela and Steiner, Andreas and Peinhaupt, Tobias and Podda, Maurizio and Schmid, Sabine and Wollina, Uwe and Biedermann, Tilo and Posch, Christian (2023) 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, 37 (5). pp. 894-906. ISSN 0926-9959, 1468-3083
Full text not available from this repository. (Request a copy)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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | STAGE-III; MULTICENTER; IPILIMUMAB; NIVOLUMAB; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Dermatologie und Venerologie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 05 Mar 2024 14:21 |
| Last Modified: | 05 Mar 2024 14:21 |
| URI: | https://pred.uni-regensburg.de/id/eprint/58823 |
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