TY  - JOUR
A1  - Koch, Elias A. T.
A1  - Petzold, Anne
A1  - Wessely, Anja
A1  - Dippel, Edgar
A1  - Gesierich, Anja
A1  - Gutzmer, Ralf
A1  - Hassel, Jessica C.
A1  - Haferkamp, Sebastian
A1  - Hohberger, Bettina
A1  - Kähler, Katharina C.
A1  - Knorr, Harald
A1  - Kreuzberg, Nicole
A1  - Leiter, Ulrike
A1  - Loquai, Carmen
A1  - Meier, Friedegund
A1  - Meissner, Markus
A1  - Mohr, Peter
A1  - Pföhler, Claudia
A1  - Rahimi, Farnaz
A1  - Schadendorf, Dirk
A1  - Schell, Beatrice
A1  - Schlaak, Max
A1  - Terheyden, Patrick
A1  - Thoms, Kai-Martin
A1  - Schuler-Thurner, Beatrice
A1  - Ugurel, Selma
A1  - Ulrich, Jens
A1  - Utikal, Jochen
A1  - Weichenthal, Michael
A1  - Ziller, Fabian
A1  - Berking, Carola
A1  - Heppt, Markus
T1  - Immune checkpoint blockade for metastatic uveal melanoma: patterns of response and survival according to the presence of hepatic and extrahepatic metastasis
JF  - Cancers
N2  - Background: Since there is no standardized and effective treatment for advanced uveal melanoma (UM), the prognosis is dismal once metastases develop. Due to the availability of immune checkpoint blockade (ICB) in the real-world setting, the prognosis of metastatic UM has improved. However, it is unclear how the presence of hepatic and extrahepatic metastasis impacts the response and survival after ICB. Methods: A total of 178 patients with metastatic UM treated with ICB were included in this analysis. Patients were recruited from German skin cancer centers and the German national skin cancer registry (ADOReg). To investigate the impact of hepatic metastasis, two cohorts were compared: patients with liver metastasis only (cohort A, n = 55) versus those with both liver and extra-hepatic metastasis (cohort B, n = 123). Data were analyzed in both cohorts for response to treatment, progression-free survival (PFS), and overall survival (OS). The survival and progression probabilities were calculated with the Kaplan–Meier method. Log-rank tests, χ\(^2\) tests, and t-tests were performed to detect significant differences between both cohorts. Results: The median OS of the overall population was 16 months (95% CI 13.4–23.7) and the median PFS, 2.8 months (95% CI 2.5–3.0). The median OS was longer in cohort B than in cohort A (18.2 vs. 6.1 months; p = 0.071). The best objective response rate to dual ICB was 13.8% and to anti-PD-1 monotherapy 8.9% in the entire population. Patients with liver metastases only had a lower response to dual ICB, yet without significance (cohort A 8.7% vs. cohort B 16.7%; p = 0.45). Adverse events (AE) occurred in 41.6%. Severe AE were observed in 26.3% and evenly distributed between both cohorts. Conclusion: The survival of this large cohort of patients with advanced UM was more favorable than reported in previous benchmark studies. Patients with both hepatic and extrahepatic metastasis showed more favorable survival and higher response to dual ICB than those with hepatic metastasis only.
KW  - uveal melanoma
KW  - immune checkpoint blockade
KW  - PD-1
KW  - CTLA-4
KW  - liver metastasis
KW  - treatment resistance
Y1  - 2021
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-242603
SN  - 2072-6694
VL  - 13
IS  - 13
ER  - 
TY  - JOUR
A1  - Haist, Maximilian
A1  - Stege, Henner
A1  - Lang, Berenice Mareen
A1  - Tsochataridou, Aikaterini
A1  - Salzmann, Martin
A1  - Mohr, Peter
A1  - Schadendorf, Dirk
A1  - Ugurel, Selma
A1  - Placke, Jan-Malte
A1  - Weichenthal, Michael
A1  - Gutzmer, Ralf
A1  - Leiter, Ulrike
A1  - Kaatz, Martin
A1  - Haferkamp, Sebastian
A1  - Berking, Carola
A1  - Heppt, Markus
A1  - Tschechne, Barbara
A1  - Schummer, Patrick
A1  - Gebhardt, Christoffer
A1  - Grabbe, Stephan
A1  - Loquai, Carmen
T1  - Response to first-line treatment with immune-checkpoint inhibitors in patients with advanced cutaneous squamous cell carcinoma: a multicenter, retrospective analysis from the German ADOReg registry
JF  - Cancers
N2  - Cutaneous squamous cell carcinoma (cSCC) is a common malignancy of the skin and has an overall favorable outcome, except for patients with an advanced stage of the disease. The efficacy of checkpoint inhibitors (CPI) for advanced cSCC has been demonstrated in recent clinical studies, but data from real-world cohorts and trial-ineligible cSCC patients are limited. We retrospectively investigated patients with advanced cSCC who have been treated with CPI in a first-line setting at eight German skin cancer centers registered within the multicenter registry ADOReg. Clinical outcome parameters including response, progression-free (PFS) and overall survival (OS), time-to-next-treatment (TTNT), and toxicity were analyzed and have been stratified by the individual immune status. Among 39 evaluable patients, the tumor response rate (rwTRR) was 48.6%, the median PFS was 29.0 months, and the median OS was not reached. In addition, 9 patients showed an impaired immune status due to immunosuppressive medication or hematological diseases. Our data demonstrated that CPI also evoked tumor responses among immunocompromised patients (rwTRR: 48.1 vs. 50.0%), although these responses less often resulted in durable remissions. In line with this, the median PFS (11 vs. 40 months, p = 0.059), TTNT (12 months vs. NR, p = 0.016), and OS (29 months vs. NR, p < 0.001) were significantly shorter for this patient cohort. CPI therapy was well tolerated in both subcohorts with 15% discontinuing therapy due to toxicity. Our real-world data show that first-line CPI therapy produced strong and durable responses among patients with advanced cSCC. Immunocompromised patients were less likely to achieve long-term benefit from anti-PD1 treatment, despite similar tumor response rates.
KW  - advanced cutaneous squamous cell carcinoma
KW  - checkpoint inhibitor therapy
KW  - cemiplimab
KW  - immunosuppression
KW  - response durability
KW  - real-world data
Y1  - 2022
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-297506
SN  - 2072-6694
VL  - 14
IS  - 22
ER  -