TY - JOUR A1 - Hecht, Markus A1 - Meier, Friedegund A1 - Zimmer, Lisa A1 - Polat, Bülent A1 - Loquai, Carmen A1 - Weishaupt, Carsten A1 - Forschner, Andrea A1 - Gutzmer, Ralf A1 - Utikal, Jochen S. A1 - Goldinger, Simone M. A1 - Geier, Michael A1 - Hassel, Jessica C. A1 - Balermpas, Panagiotis A1 - Kiecker, Felix A1 - Rauschenberg, Ricarda A1 - Dietrich, Ursula A1 - Clemens, Patrick A1 - Berking, Carola A1 - Grabenbauer, Gerhard A1 - Schadendorf, Dirk A1 - Grabbe, Stephan A1 - Schuler, Gerold A1 - Fietkau, Rainer A1 - Distel, Luitpold V. A1 - Heinzerling, Lucie T1 - Clinical outcome of concomitant vs interrupted BRAF inhibitor therapy during radiotherapy in melanoma patients JF - British Journal of Cancer N2 - Background: Concomitant radiation with BRAF inhibitor (BRAFi) therapy may increase radiation-induced side effects but also potentially improve tumour control in melanoma patients. Methods: A total of 155 patients with BRAF-mutated melanoma from 17 European skin cancer centres were retrospectively analysed. Out of these, 87 patients received concomitant radiotherapy and BRAFi (59 vemurafenib, 28 dabrafenib), while in 68 patients BRAFi therapy was interrupted during radiation (51 vemurafenib, 17 dabrafenib). Overall survival was calculated from the first radiation (OSRT) and from start of BRAFi therapy (OSBRAFi). Results: The median duration of BRAFi treatment interruption prior to radiotherapy was 4 days and lasted for 17 days. Median OSRT and OSBRAFi in the entire cohort were 9.8 and 12.6 months in the interrupted group and 7.3 and 11.5 months in the concomitant group (P=0.075/P=0.217), respectively. Interrupted vemurafenib treatment with a median OSRT and OSBRAFi of 10.1 and 13.1 months, respectively, was superior to concomitant vemurafenib treatment with a median OSRT and OSBRAFi of 6.6 and 10.9 months (P=0.004/P=0.067). Interrupted dabrafenib treatment with a median OSRT and OSBRAFi of 7.7 and 9.8 months, respectively, did not differ from concomitant dabrafenib treatment with a median OSRT and OSBRAFi of 9.9 and 11.6 months (P=0.132/P=0.404). Median local control of the irradiated area did not differ in the interrupted and concomitant BRAFi treatment groups (P=0.619). Skin toxicity of grade ≥2 (CTCAE) was significantly increased in patients with concomitant vemurafenib compared to the group with treatment interruption (P=0.002). Conclusions: Interruption of vemurafenib treatment during radiation was associated with better survival and less toxicity compared to concomitant treatment. Due to lower number of patients, the relevance of treatment interruption in dabrafenib treated patients should be further investigated. The results of this analysis indicate that treatment with the BRAFi vemurafenib should be interrupted during radiotherapy. Prospective studies are desperately needed. KW - radiation KW - radiotherapy KW - BRAF KW - vemurafenib KW - dabrafenib Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-227970 VL - 118 ER - TY - JOUR A1 - Lodde, Georg A1 - Forschner, Andrea A1 - Hassel, Jessica A1 - Wulfken, Lena M. A1 - Meier, Friedegund A1 - Mohr, Peter A1 - Kähler, Katharina A1 - Schilling, Bastian A1 - Loquai, Carmen A1 - Berking, Carola A1 - Hüning, Svea A1 - Schatton, Kerstin A1 - Gebhardt, Christoffer A1 - Eckardt, Julia A1 - Gutzmer, Ralf A1 - Reinhardt, Lydia A1 - Glutsch, Valerie A1 - Nikfarjam, Ulrike A1 - Erdmann, Michael A1 - Stang, Andreas A1 - Kowall, Bernd A1 - Roesch, Alexander A1 - Ugurel, Selma A1 - Zimmer, Lisa A1 - Schadendorf, Dirk A1 - Livingstone, Elisabeth T1 - Factors influencing the adjuvant therapy decision: results of a real-world multicenter data analysis of 904 melanoma patients JF - Cancers N2 - Adjuvant treatment of melanoma patients with immune-checkpoint inhibition (ICI) and targeted therapy (TT) significantly improved recurrence-free survival. This study investigates the real-world situation of 904 patients from 13 German skin cancer centers with an indication for adjuvant treatment since the approval of adjuvant ICI and TT. From adjusted log-binomial regression models, we estimated relative risks for associations between various influence factors and treatment decisions (adjuvant therapy yes/no, TT vs. ICI in BRAF mutant patients). Of these patients, 76.9% (95% CI 74–80) opted for a systemic adjuvant treatment. The probability of starting an adjuvant treatment was 26% lower in patients >65 years (RR 0.74, 95% CI 68–80). The most common reasons against adjuvant treatment given by patients were age (29.4%, 95% CI 24–38), and fear of adverse events (21.1%, 95% CI 16–28) and impaired quality of life (11.9%, 95% CI 7–16). Of all BRAF-mutated patients who opted for adjuvant treatment, 52.9% (95% CI 47–59) decided for ICI. Treatment decision for TT or ICI was barely associated with age, gender and tumor stage, but with comorbidities and affiliated center. Shortly after their approval, adjuvant treatments have been well accepted by physicians and patients. Age plays a decisive role in the decision for adjuvant treatment, while pre-existing autoimmune disease and regional differences influence the choice between TT or ICI. KW - melanoma KW - adjuvant treatment KW - checkpoint blocker KW - targeted therapy KW - BRAF KW - PD-1 Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-239583 SN - 2072-6694 VL - 13 IS - 10 ER - 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 - 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 - 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 V. T1 - Immune checkpoint blockade for metastatic uveal melanoma: re-induction following resistance or toxicity JF - Cancers N2 - Re-induction with immune checkpoint blockade (ICB) needs to be considered in many patients with uveal melanoma (UM) due to limited systemic treatment options. Here, we provide hitherto the first analysis of ICB re-induction in UM. A total of 177 patients with metastatic UM treated with ICB were included from German skin cancer centers and the German national skin cancer registry (ADOReg). To investigate the impact of ICB re-induction, two cohorts were compared: patients who received at least one ICB re-induction (cohort A, n = 52) versus those who received only one treatment line of ICB (cohort B, n = 125). In cohort A, a transient benefit of overall survival (OS) was observed at 6 and 12 months after the treatment start of ICB. There was no significant difference in OS between both groups (p = 0.1) with a median OS of 16.2 months (cohort A, 95% CI: 11.1–23.8) versus 9.4 months (cohort B, 95% CI: 6.1–14.9). Patients receiving re-induction of ICB (cohort A) had similar response rates compared to those receiving ICB once. Re-induction of ICB may yield a clinical benefit for a small subgroup of patients even after resistance or development of toxicities. KW - uveal melanoma KW - immune checkpoint blockade KW - PD-1 KW - CTLA-4 KW - re-induction KW - treatment resistance KW - toxicity Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-254814 SN - 2072-6694 VL - 14 IS - 3 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 -