Open Access

Simple Summary: The introduction of BRAF/MEK-directed targeted therapy (TT) has significantly improved the management of patients with advanced BRAF-V600-mutant melanoma. Although resistance occurs, there is a subgroup of patients showing a complete response (CR) to TT and who maintain durable disease control. For these patients with durable CR, it is not clear whether it is safe to cease therapy. In this retrospective, multicenter study we have analyzed 37 patients who received TT and achieved a CR upon treatment. We identified 15 patients with a durable CR to TT. Overall, patients who discontinued TT (n = 26) were at higher risk of tumor progression compared to patients receiving ongoing TT. Sustained CR was however not restricted to patients with ongoing TT (n = 11) but was also found in patients who ceased TT (n = 4). Finally, our analysis indicated which patients with an initial CR might be most likely to maintain durable CR upon discontinuation of TT. Abstract: The advent of BRAF/MEK inhibitors (BRAFi/MEKi) has significantly improved progression-free (PFS) and overall survival (OS) for patients with advanced BRAF-V600-mutant melanoma. Long-term survivors have been identified particularly among patients with a complete response (CR) to BRAF/MEK-directed targeted therapy (TT). However, it remains unclear which patients who achieved a CR maintain a durable response and whether treatment cessation might be a safe option in these patients. Therefore, this study investigated the impact of treatment cessation on the clinical course of patients with a CR upon BRAF/MEK-directed-TT. We retrospectively selected patients with BRAF-V600-mutant advanced non-resectable melanoma who had been treated with BRAFi ± MEKi therapy and achieved a CR upon treatment out of the multicentric skin cancer registry ADOReg. Data on baseline patient characteristics, duration of TT, treatment cessation, tumor progression (TP) and response to second-line treatments were collected and analyzed. Of 461 patients who received BRAF/MEK-directed TT 37 achieved a CR. TP after initial CR was observed in 22 patients (60%) mainly affecting patients who discontinued TT (n = 22/26), whereas all patients with ongoing TT (n = 11) maintained their CR. Accordingly, patients who discontinued TT had a higher risk of TP compared to patients with ongoing treatment (p < 0.001). However, our data also show that patients who received TT for more than 16 months and who discontinued TT for other reasons than TP or toxicity did not have a shorter PFS compared to patients with ongoing treatment. Response rates to second-line treatment being initiated in 21 patients, varied between 27% for immune-checkpoint inhibitors (ICI) and 60% for BRAFi/MEKi rechallenge. In summary, we identified a considerable number of patients who achieved a CR upon BRAF/MEK-directed TT in this contemporary real-world cohort of patients with BRAF-V600-mutant melanoma. Sustained PFS was not restricted to ongoing TT but was also found in patients who discontinued TT.

Der Silberreiher trat bis zum Ende des 20. Jahrhunderts in Deutschland nur als Ausnahmeerscheinung auf, zählt seither jedoch zu den regelmäßigen Gastvögeln im Winterhalbjahr. Vereinzelt kommt es auch zu Übersommerungen. Die Herkunft dieser Vögel ist weitgehend unbekannt. Erstmals in Mitteleuropa konnte von uns ein Silberreiher mit einem Satellitensender versehen und von Februar 2007 bis zum Ende der Datenaufnahme für diesen Bericht im April 2010 verfolgt werden. Der Vogel überwinterte dreimal in Ostdeutschland und hielt sich 2008 und 2009 während der Brutzeit sehr ortstreu über mehrere Monate in der Ukraine auf. Diesen ortstreuen Phasen zur Brutzeit folgten jeweils nachbrutzeitliche Wanderungen über mehrere 100 km, die als Mauserzug interpretiert werden. Erst im Laufe des Oktobers fand der eigentliche Zug ins Überwinterungsgebiet statt. Ringfunde aus der Zeit nach dem deutlichen Bestandsanstieg in Deutschland geben außerdem erste Hinweise darauf, dass die im Nordosten Deutschlands als Gastvögel auftretenden Silberreiher auch aus Westfrankreich und Polen stammen können und dass zumindest in Süddeutschland Vögel aus den traditionellen ungarischen Brutgebieten auftreten.