Real‐world outcomes using PD‐1 antibodies and BRAF + MEK inhibitors for adjuvant melanoma treatment from 39 skin cancer centers in Germany, Austria and Switzerland
Authors: Schumann Katharina , Mauch Cornelia , Klespe Kai‐Christian , Loquai Carmen , Nikfarjam Ulrike , Schlaak Max , Akçetin Larissa , Kölblinger Peter , Hoellwerth Magdalena , Meissner Markus , Mengi Guelcin , Braun Andreas Dominik , Mengoni Miriam , Dummer Reinhard , Mangana Joanna , Sindrilaru Mihaela‐Anca , Radmann Dan , Hafner Christine , Freund Johann , Rappersberger Klemens , Weihsengruber Felix , Meiss Frank , Reinhardt Lydia , Meier Friedegund , Rainer Barbara , Richtig Erika , Ressler Julia Maria , Höller Christoph , Eigentler Thomas , Amaral Teresa , Peitsch Wiebke K. , Hillen Uwe , Harth Wolfgang , Ziller Fabian , Schatton Kerstin , Gambichler Thilo , Susok Laura , Maul Lara Valeska , Läubli Heinz , Debus Dirk , Weishaupt Carsten , Börger Sevil , Sievers Katharina , Haferkamp Sebastian , Zenderowski Veronika , Nguyen Van Anh , Wanner Marina , Gutzmer Ralf , Terheyden Patrick , Kähler Katharina , Emmert Steffen , Thiem Alexander , Sachse Michael , Gercken‐Riedel Silke , Kaune Kjell Matthias , Thoms Kai‐Martin , Heinzerling Lucie , Heppt Markus Vincent , Tratzmiller Sabine , Hoetzenecker Wolfram , Öllinger Angela , Steiner Andreas , Peinhaupt Tobias , Podda Maurizio , Schmid Sabine , Wollina Uwe , Biedermann Tilo , Posch Christian 
Published: November 2022

Background

Programmed 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.

Methods

Multicenter, 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.

Results

In 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.

Conclusions

Despite 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.