Introduction - For rare skin cancers, few data exist on the outcome of systemic therapies, particularly immune checkpoint inhibition (ICI). The present study analysed the real-world use of different systemic therapies including ICI, and its outcome in patients with advanced rare skin cancers. - Methods - This retrospective multicenter study included patients who received systemic therapy for advanced, non-resectable cutaneous angiosarcoma (AS), Kaposi sarcoma (KS), pleomorphic dermal sarcoma (PDS), or cutaneous adnexal carcinoma (CAC). Study endpoints were best overall response (BOR), progression-free survival (PFS) and overall survival (OS). - Results - 209 patients (77 AS; 81 KS; 14 PDS; and 37 CAC) from 30 centers were included. As first-line treatment AS and KS patients predominantly received chemotherapy (77.9%; 63.0%), while PDS and CAC patients mostly received ICI (64.4%; 43.2%). BOR in first-line across all therapy types was 65.5% in KS, 50.0% in PDS, 41.6% in AS, and 10.8% in CAC. BOR for ICI was 66.6% for PDS, 58.3% for AS, 33.3% for KS, and 4.3% for CAC, irrespective of treatment line. 1-year PFS rate upon any first-line therapy was 70.7% for PDS, 45.7% for KS, 25.6% for AS, and 18.5% for CAC (p<0.001). 1-year tumor-specific OS rate was 97.3% in KS, 84.2% in AS, 67.7% in PDS, and 65.4% in CAC (p<0.001). - Conclusions - Type and outcome of systemic therapy differed between cancer entities. Efficacy of ICI was high in PDS and AS, moderate in KS, and low in CAC. Patients with advanced CAC revealed an extremely poor prognosis regardless of the type of therapy used.
European journal of cancer Amsterdam [u.a.] : Elsevier, 1992 228(2025) vom: Okt., Artikel-ID 115750, Seite 1-10
von Jan Alexander Stratmann ; Friederike Cornelia Althoff ; Paula Doebel ; Jacqueline Rauh ; Arne Trummer ; Ali Nuri Hünerlitürkoglu ; Nikolaj Frost ; Hüsameddin Yildirim ; Petros Christopoulos ; Oswald Burkhard ; Christian Meyer zum Büschenfelde ; Aaron Becker von Rose ; Jürgen Alt ; Sven Aries ; Maximilian Webendörfer ; Stefan Kaldune ; Mark Uhlenbruch ; Guergana Tritchkova ; Cornelius Waller ; Achim Rittmeyer ; Petra Hoffknecht ; Jan Braess ; Hans-Georg Kopp ; Christian Grohé ; Monica Schäfer ; Christian Schumann ; Frank Griesinger ; Jonas Kuon ; Martin Sebastian ; Niels Reinmuth
Background - Sotorasib is a first-in-class KRAS p.G12C-inhibitor that has entered clinical trials in pretreated patients with non-small cell lung cancer (NSCLC) in 2018. First response rates were promising in the CodeBreaK trials. It remains unclear whether response to sotorasib and outcomes differ in a real-world setting when including patients underrepresented in clinical trials. - Methods - Patients with KRAS p.G12C-mutated advanced or metastatic NSCLC received sotorasib within the German multicenter sotorasib compassionate use program between 2020 to 2022. Data on efficacy, tolerability, and survival were analyzed in the full cohort and in subgroups of special interest such as co-occurring mutations and across PD-L1 expression levels. - Results - We analyzed 163 patients who received sotorasib after a median of two treatment lines (range, 0 to 7). Every fourth patient had a poor performance status and 38% had brain metastases (BM). The objective response rate was 38.7%. The median overall survival was 9.8 months (95% CI, 6.5 to not reached). Median real-world (rw) progression-free survival was 4.8 months (9% CI, 3.9 to 5.9). Dose reductions and permanent discontinuation were necessary in 35 (21.5%) and 7 (4.3%) patients, respectively. Efficacy seems to be influenced by PD-L1 expression and a co-occurring KEAP1 mutation. KEAP1 was associated with an inferior survival. Other factors such as BM, STK11, and TP53 mutations had no impact on response and survival. - Conclusion - First results from a real-world population confirm promising efficacy of sotorasib for the treatment of advanced KRAS p.G12C-mutated NSCLC. Patients with co-occurring KEAP1 mutations seem to derive less benefit.
European journal of cancer Amsterdam [u.a.] : Elsevier, 1992 201(2024), Seite 113911
von Julie George ; Lukas Maas ; Nima Abedpour ; Maria Cartolano ; Laura Kaiser ; Rieke Nila Fischer ; Andreas H. Scheel ; Jan-Philipp Weber ; Martin Hellmich ; Graziella Bosco ; Caroline Volz ; Christian Müller ; Ilona Dahmen ; Felix John ; Cleidson Padua Alves ; Lisa Werr ; Jens Peter Panse ; Martin Kirschner ; Walburga Engel-Riedel ; Jessica Jürgens ; Erich Stoelben ; Michael Brockmann ; Stefan Grau ; Martin Sebastian ; Jan Alexander Stratmann ; Jens Kern ; Horst-Dieter Hummel ; Balazs Hegedus ; Martin Schuler ; Till Plönes ; Clemens Aigner ; Thomas Elter ; Karin Toepelt ; Yon-Dschun Ko ; Sylke Kurz ; Christian Grohé ; Monika Serke ; Katja Anne Höpker ; Lars Gerd Hagmeyer ; Fabian Doerr ; Khosro Hekmath ; Judith Strapatsas ; Karl-Otto Kambartel ; Geothy Chakupurakal ; Annette Hülsmeyer ; Franz-Georg Bauernfeind ; Frank Griesinger ; Anne Lüers ; Wiebke Dirks ; Rainer Gerhard Wiewrodt ; Andrea Luecke ; Ernst Michael Rodermann ; Andreas Diel ; Volker Hagen ; Kai Severin ; Roland Ullrich ; Christian Reinhardt ; Alexander Quaas ; Magdalena Bogus ; Cornelius Courts ; Peter Nürnberg ; Kerstin Becker ; Viktor Achter ; Reinhard Büttner ; Jürgen Wolf ; Martin Peifer ; Roman Thomas
von Bas van Maren ; Christian Maushake ; Jan Willem Moll ; Daan van Keulen ; Jens Jürges ; Julia Vroom ; Henk Schuttelaars ; Theo Gerkema ; Kirstin Schulz ; Thomas H. Badewien ; Michaela Gerriets ; Andreas Engels ; Andreas Wurpts ; Dennis Oberrecht ; Andrew J. Manning ; Taylor Bailey ; Lauren Ross ; Volker Mohrholz ; Dante M. L. Horemans ; Marius Becker ; Dirk Post ; Charlotte Schmidt ; Petra J. T. Dankers
