12621
2012
eng
2091-2103
11
61
article
1
2016-01-29
--
--
Survivin-specific T-cell reactivity correlates with tumor response and patient survival: a phase-II peptide vaccination trial in metastatic melanoma
Background
Therapeutic vaccination directed to induce an anti-tumoral T-cell response is a field of extensive investigation in the treatment of melanoma. However, many vaccination trials in melanoma failed to demonstrate a correlation between the vaccine-specific immune response and therapy outcome. This has been mainly attributed to immune escape by antigen loss, rendering us in the need of new vaccination targets.
Patients and methods
This phase-II trial investigated a peptide vaccination against survivin, an oncogenic inhibitor-of-apoptosis protein crucial for the survival of tumor cells, in HLA-A1/-A2/-B35-positive patients with treatment-refractory stage-IV metastatic melanoma. The study endpoints were survivin-specific T-cell reactivity (SSTR), safety, response, and survival (OS).
Results
Sixty-one patients (ITT) received vaccination therapy using three different regimens. 55 patients (PP) were evaluable for response and survival, and 41/55 for SSTR. Patients achieving progression arrest (CR + PR + SD) more often showed SSTRs than patients with disease progression (p = 0.0008). Patients presenting SSTRs revealed a prolonged OS (median 19.6 vs. 8.6 months; p = 0.0077); multivariate analysis demonstrated SSTR as an independent predictor of survival (p = 0.013). The induction of SSTRs was associated with gender (female vs. male; p = 0.014) and disease stage (M1a/b vs. M1c; p = 0.010), but not with patient age, HLA type, performance status, or vaccination regimen.
Conclusion
Survivin-specific T-cell reactivities strongly correlate with tumor response and patient survival, indicating that vaccination with survivin-derived peptides is a promising treatment strategy in melanoma.
Cancer Immunology, Immunotherapy
10.1007/s00262-012-1266-9
urn:nbn:de:bvb:20-opus-126215
Cancer Immunology Immunotherapy (2012) 61:2091–2103 DOI 10.1007/s00262-012-1266-9
Jürgen C. Becker
Mads H. Andersen
Valeska Hofmeister-Müller
Marion Wobser
Lidia Frey
Christiane Sandig
Steffen Walter
Harpreet Singh-Jasuja
Eckhart Kämpgen
Andreas Opitz
Marc Zapatka
Eva-B. Bröcker
Per thor Straten
David Schrama
Selma Ugurel
eng
uncontrolled
peptide vaccination
eng
uncontrolled
therapy
eng
uncontrolled
survivin T-cell reactivity
eng
uncontrolled
melanoma
Medizin und Gesundheit
open_access
Klinik und Poliklinik für Dermatologie, Venerologie und Allergologie
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/12621/262_2012_Article_1266.pdf
12483
2012
eng
2091-2103
11
61
article
1
2016-01-22
--
--
Survivin-specific T-cell reactivity correlates with tumor response and patient survival: a phase-II peptide vaccination trial in metastatic melanoma
Background
Therapeutic vaccination directed to induce an anti-tumoral T-cell response is a field of extensive investigation in the treatment of melanoma. However, many vaccination trials in melanoma failed to demonstrate a correlation between the vaccine-specific immune response and therapy outcome. This has been mainly attributed to immune escape by antigen loss, rendering us in the need of new vaccination targets.
Patients and methods
This phase-II trial investigated a peptide vaccination against survivin, an oncogenic inhibitor-of-apoptosis protein crucial for the survival of tumor cells, in HLA-A1/-A2/-B35-positive patients with treatment-refractory stage-IV metastatic melanoma. The study endpoints were survivin-specific T-cell reactivity (SSTR), safety, response, and survival (OS).
Results
Sixty-one patients (ITT) received vaccination therapy using three different regimens. 55 patients (PP) were evaluable for response and survival, and 41/55 for SSTR. Patients achieving progression arrest (CR + PR + SD) more often showed SSTRs than patients with disease progression (p = 0.0008). Patients presenting SSTRs revealed a prolonged OS (median 19.6 vs. 8.6 months; p = 0.0077); multivariate analysis demonstrated SSTR as an independent predictor of survival (p = 0.013). The induction of SSTRs was associated with gender (female vs. male; p = 0.014) and disease stage (M1a/b vs. M1c; p = 0.010), but not with patient age, HLA type, performance status, or vaccination regimen.
Conclusion
Survivin-specific T-cell reactivities strongly correlate with tumor response and patient survival, indicating that vaccination with survivin-derived peptides is a promising treatment strategy in melanoma.
Cancer Immunology, Immunotherapy
10.1007/s00262-012-1266-9
urn:nbn:de:bvb:20-opus-124830
Cancer Immunology Immunotherapy (2012) 61:2091–2103 DOI 10.1007/s00262-012-1266-9
Jürgen C. Becker
Mads H. Andersen
Valeska Hofmeister-Müller
Marion Wobser
Lidia Frey
Christiane Sandig
Steffen Walter
Harpreet Singh-Jasuja
Eckhart Kämpgen
Andreas Opitz
Marc Zapatka
Eva-B. Bröcker
Per thor Straten
David Schrama
Selma Ugurel
eng
uncontrolled
peptide vaccination
eng
uncontrolled
melanoma
eng
uncontrolled
survivin
eng
uncontrolled
T-cell reactivity
eng
uncontrolled
therapy
Krankheiten
open_access
Klinik und Poliklinik für Dermatologie, Venerologie und Allergologie
Institut für Klinische Transfusionsmedizin und Hämotherapie
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/12483/Becker_2Fs00262-012-1266-9.pdf
12060
2014
eng
47
1
article
1
2015-10-21
--
--
STAT3 Single Nucleotide Polymorphism rs4796793 SNP Does Not Correlate with Response to Adjuvant IFNα Therapy in Stage III Melanoma Patients
Interferon alpha (IFNα) is approved for adjuvant treatment of stage III melanoma in Europe and the US. Its clinical efficacy, however, is restricted to a subpopulation of patients while side effects occur in most of treated patients. Thus, the identification of predictive biomarkers would be highly beneficial to improve the benefit to risk ratio. In this regard, STAT3 is important for signaling of the IFNα receptor. Moreover, the STAT3 single-nucleotide polymorphism (SNP) rs4796793 has recently been reported to be associated with IFNα sensitivity in metastatic renal cell carcinoma. To translate this notion to melanoma, we scrutinized the impact of rs4796793 functionally and clinically in this cancer. Interestingly, melanoma cells carrying the minor allele of rs4796793 were the most sensitive to IFNα in vitro. However, we did not detect a correlation between SNP genotype and STAT3 mRNA expression for either melanoma cells or for peripheral blood lymphocytes. Next, we analyzed the impact of rs4796793 on the clinical outcome of 259 stage III melanoma patients of which one-third had received adjuvant IFNα treatment. These analyses did not reveal a significant association between the STAT3 rs4796793 SNP and patients' progression free or overall survival when IFNα treated and untreated patients were compared. In conclusion, STAT3 rs4796793 SNP is no predictive marker for the efficacy of adjuvant IFNα treatment in melanoma patients.
Frontiers in Medicine
10.3389/fmed.2014.00047
2296-858X
25593920
urn:nbn:de:bvb:20-opus-120602
Frontiers in Medicine 1:47. doi: 10.3389/fmed.2014.00047
David Schrama
Selma Ugurel
Antje Sucker
Cathrin Ritter
Marc Zapatka
Dirk Schadendorf
Jürgen Christian Becker
eng
uncontrolled
predictive marker
eng
uncontrolled
single nucleotide polymorphism
eng
uncontrolled
melanoma
eng
uncontrolled
interferon
eng
uncontrolled
STAT3
Medizin und Gesundheit
open_access
Klinik und Poliklinik für Dermatologie, Venerologie und Allergologie
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/12060/106_Schrama_Frontiers_in_Medicine.pdf
12009
2014
eng
94-96
94
article
1
2015-10-12
--
--
Denileukin Diftitox plus Total Skin Electron Beam Radiation in Patients with Treatment-refractory Cutaneous T-cell Lymphoma (Mycosis Fungoides): Report of Four Cases
Mycosis fungoides (MF) is the most common cutaneous T-cell lymphoma (CTCL) (1). Most patients initially respond well to standard therapy, but advanced MF is often treatment refractory. Thus, a combination of the available treatment options is an important strategy. Total skin electron beam radiation (TSEB) is effective in MF, with a complete remission rate of up to 90% in the early stages. However, in patients with more advanced stages, remission rates are considerably lower (2, 3). Denileukin diftitox (DD) (Ontak®) is a recombinant fusion protein of the receptor-binding domain of interleukin (IL)-2 and the enzymatic and translocation domains of diphtheria toxin (4). It targets the alpha-subunit of the IL-2-receptor (CD25). There are no reports on this combination therapy in MF.
Acta Dermato-Venereologica
10.2340/00015555-1627
urn:nbn:de:bvb:20-opus-120091
Der Zugang zum Volltext ist aus rechtlichen Gründen gesperrt.
Acta Dermato-Venereologica 2014; 94: 94–96. doi: 10.2340/00015555-1627
Deutsches Urheberrecht
Kristina Buder
Philip A. Müller
Gabriele Beekmann
Selma Ugurel
Eva-Bettina Bröcker
Jürgen C. Becker
eng
uncontrolled
lymphoma
Medizin und Gesundheit
Klinik und Poliklinik für Dermatologie, Venerologie und Allergologie
Universität Würzburg
24260
2021
eng
13
13
article
1
--
2021-07-04
--
Immune checkpoint blockade for metastatic uveal melanoma: patterns of response and survival according to the presence of hepatic and extrahepatic metastasis
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.
Cancers
2072-6694
10.3390/cancers13133359
urn:nbn:de:bvb:20-opus-242603
2021-08-01T12:41:39+00:00
sword
swordwue
attachment; filename=deposit.zip
91cc7a75e892e08866190d0854928aa5
Cancers (2021) 13:13, 3359. https://doi.org/10.3390/cancers13133359
false
true
CC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International
Elias A. T. Koch
Anne Petzold
Anja Wessely
Edgar Dippel
Anja Gesierich
Ralf Gutzmer
Jessica C. Hassel
Sebastian Haferkamp
Bettina Hohberger
Katharina C. Kähler
Harald Knorr
Nicole Kreuzberg
Ulrike Leiter
Carmen Loquai
Friedegund Meier
Markus Meissner
Peter Mohr
Claudia Pföhler
Farnaz Rahimi
Dirk Schadendorf
Beatrice Schell
Max Schlaak
Patrick Terheyden
Kai-Martin Thoms
Beatrice Schuler-Thurner
Selma Ugurel
Jens Ulrich
Jochen Utikal
Michael Weichenthal
Fabian Ziller
Carola Berking
Markus Heppt
eng
uncontrolled
uveal melanoma
eng
uncontrolled
immune checkpoint blockade
eng
uncontrolled
PD-1
eng
uncontrolled
CTLA-4
eng
uncontrolled
liver metastasis
eng
uncontrolled
treatment resistance
Medizin und Gesundheit
open_access
Klinik und Poliklinik für Dermatologie, Venerologie und Allergologie
Import
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/24260/cancers-13-03359-v2.pdf
23958
2021
eng
10
13
article
1
--
2021-05-12
--
Factors influencing the adjuvant therapy decision: results of a real-world multicenter data analysis of 904 melanoma patients
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.
Cancers
2072-6694
10.3390/cancers13102319
urn:nbn:de:bvb:20-opus-239583
2021-06-11T13:00:27+00:00
sword
swordwue
attachment; filename=deposit.zip
7243a460afe95bdf3dec8fbcdb2dccfe
Cancers (2021) 13:10, 2319. https://doi.org/10.3390/cancers13102319
false
true
CC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International
Georg Lodde
Andrea Forschner
Jessica Hassel
Lena M. Wulfken
Friedegund Meier
Peter Mohr
Katharina Kähler
Bastian Schilling
Carmen Loquai
Carola Berking
Svea Hüning
Kerstin Schatton
Christoffer Gebhardt
Julia Eckardt
Ralf Gutzmer
Lydia Reinhardt
Valerie Glutsch
Ulrike Nikfarjam
Michael Erdmann
Andreas Stang
Bernd Kowall
Alexander Roesch
Selma Ugurel
Lisa Zimmer
Dirk Schadendorf
Elisabeth Livingstone
eng
uncontrolled
melanoma
eng
uncontrolled
adjuvant treatment
eng
uncontrolled
checkpoint blocker
eng
uncontrolled
targeted therapy
eng
uncontrolled
BRAF
eng
uncontrolled
PD-1
Medizin und Gesundheit
open_access
Klinik und Poliklinik für Dermatologie, Venerologie und Allergologie
Import
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/23958/cancers-13-02319-v2.pdf
25481
2022
eng
3
14
article
1
--
2022-01-20
--
Immune checkpoint blockade for metastatic uveal melanoma: re-induction following resistance or toxicity
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.
Cancers
2072-6694
10.3390/cancers14030518
urn:nbn:de:bvb:20-opus-254814
2022-02-05T19:45:54+00:00
sword
swordwue
attachment; filename=deposit.zip
849f39c3407d4919e8e3cc88296a4ce5
Cancers (2022) 14:3, 518. https://doi.org/10.3390/cancers14030518
false
true
CC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International
Elias A. T. Koch
Anne Petzold
Anja Wessely
Edgar Dippel
Anja Gesierich
Ralf Gutzmer
Jessica C. Hassel
Sebastian Haferkamp
Katharina C. Kähler
Harald Knorr
Nicole Kreuzberg
Ulrike Leiter
Carmen Loquai
Friedegund Meier
Markus Meissner
Peter Mohr
Claudia Pföhler
Farnaz Rahimi
Dirk Schadendorf
Beatrice Schell
Max Schlaak
Patrick Terheyden
Kai-Martin Thoms
Beatrice Schuler-Thurner
Selma Ugurel
Jens Ulrich
Jochen Utikal
Michael Weichenthal
Fabian Ziller
Carola Berking
Markus V. Heppt
eng
uncontrolled
uveal melanoma
eng
uncontrolled
immune checkpoint blockade
eng
uncontrolled
PD-1
eng
uncontrolled
CTLA-4
eng
uncontrolled
re-induction
eng
uncontrolled
treatment resistance
eng
uncontrolled
toxicity
Medizin und Gesundheit
open_access
Klinik und Poliklinik für Dermatologie, Venerologie und Allergologie
Import
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/25481/cancers-14-00518-v2.pdf
26563
2021
eng
2087-2093
7
70
article
1
--
--
--
Activity of ipilimumab plus nivolumab in avelumab-refractory Merkel cell carcinoma
Background
Merkel cell carcinoma (MCC) is a rare and aggressive neuroendocrine cutaneous malignancy with poor prognosis. In Europe, approved systemic therapies are limited to the PD-L1 inhibitor avelumab. For avelumab-refractory patients, efficient and safe treatment options are lacking.
Methods
At three different sites in Germany, clinical and molecular data of patients with metastatic MCC being refractory to the PD-L1 inhibitor avelumab and who were later on treated with combined IPI/NIVO were retrospectively collected and evaluated.
Results
Five patients treated at three different academic sites in Germany were enrolled. Three out of five patients investigated for this report responded to combined IPI/NIVO according to RECIST 1.1. Combined immunotherapy was well tolerated without any grade II or III immune-related adverse events. Two out of three responders to IPI/NIVO received platinum-based chemotherapy in between avelumab and combined immunotherapy.
Conclusion
In this small retrospective study, we observed a high response rate and durable responses to subsequent combined immunotherapy with IPI/NIVO in avelumab-refractory metastatic MCC patients. In conclusion, our data suggest a promising activity of second- or third-line PD-1- plus CTLA-4-blockade in patients with anti-PD-L1-refractory MCC.
Cancer Immunology, Immunotherapy
14320851
10.1007/s00262-020-02832-0
33439294
urn:nbn:de:bvb:20-opus-265635
publish
Cancer Immunology, Immunotherapy 2021, 70(7):2087-2093. DOI: 10.1007/s00262-020-02832-0
false
true
CC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International
Valerie Glutsch
Hermann Kneitz
Anja Gesierich
Matthias Goebeler
Sebastian Haferkamp
Jürgen C. Becker
Selma Ugurel
Bastian Schilling
eng
uncontrolled
ipilimumab
eng
uncontrolled
Merkel cell carcinoma
eng
uncontrolled
resistance
eng
uncontrolled
avelumab
eng
uncontrolled
nivolumab
Medizin und Gesundheit
open_access
Klinik und Poliklinik für Dermatologie, Venerologie und Allergologie
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/26563/Glutsch_Immunology.pdf
30461
2022
eng
11
10
article
1
--
2022-11-30
--
Ipilimumab plus nivolumab in avelumab-refractory Merkel cell carcinoma: a multicenter study of the prospective skin cancer registry ADOREG
Merkel cell carcinoma is a rare, highly aggressive skin cancer with neuroendocrine differentiation. Immune checkpoint inhibition has significantly improved treatment outcomes in metastatic disease with response rates to programmed cell death protein 1/programmed cell death 1 ligand 1 (PD-1/PD-L1) inhibition of up to 62%. However, primary and secondary resistance to PD-1/PD-L1 inhibition remains a so far unsolved clinical challenge since effective and safe treatment options for these patients are lacking.Fourteen patients with advanced (non-resectable stage III or stage IV, Union international contre le cancer 2017) Merkel cell carcinoma with primary resistance to the PD-L1 inhibitor avelumab receiving subsequent therapy (second or later line) with ipilimumab plus nivolumab (IPI/NIVO) were identified in the prospective multicenter skin cancer registry ADOREG. Five of these 14 patients were reported previously and were included in this analysis with additional follow-up. Overall response rate, progression-free survival (PFS), overall survival (OS) and adverse events were analyzed.All 14 patients received avelumab as first-line treatment. Thereof, 12 patients had shown primary resistance with progressive disease in the first tumor assessment, while two patients had initially experienced a short-lived stabilization (stable disease). Six patients had at least one systemic treatment in between avelumab and IPI/NIVO. In total, 7 patients responded to IPI/NIVO (overall response rate 50%), and response was ongoing in 4 responders at last follow-up. After a median follow-up of 18.85 months, median PFS was 5.07 months (95% CI 2.43—not available (NA)), and median OS was not reached. PFS rates at 12 months and 24 months were 42.9% and 26.8 %, respectively. The OS rate at 36 months was 64.3%. Only 3 (21%) patients did not receive all 4 cycles of IPI/NIVO due to immune-related adverse events.In this multicenter evaluation, we observed high response rates, a durable benefit and promising OS rates after treatment with later-line combined IPI/NIVO. In conclusion, our patient cohort supports our prior findings with an encouraging activity of second-line or later-line IPI/NIVO in patients with anti-PD-L1-refractory Merkel cell carcinoma.
Journal for ImmunoTherapy of Cancer
2051-1426
10.1136/jitc-2022-005930
36450381
urn:nbn:de:bvb:20-opus-304613
2023-03-14T05:59:39+00:00
sword
swordwue
attachment; filename=deposit.zip
8860b5ad97401dd18be8650cbadf6222
Journal for ImmunoTherapy of Cancer (2022) 10:11, e005930. doi:10.1136/jitc-2022-005930
false
true
CC BY-NC: Creative-Commons-Lizenz: Namensnennung, Nicht kommerziell 4.0 International
Valerie Glutsch
Patrick Schummer
Hermann Kneitz
Anja Gesierich
Matthias Goebeler
Detlef Klein
Christian Posch
Christoffer Gebhardt
Sebastian Haferkamp
Lisa Zimmer
Jürgen C Becker
Ulrike Leiter
Michael Weichenthal
Dirk Schadendorf
Selma Ugurel
Bastian Schilling
eng
uncontrolled
Skin Neoplasms
eng
uncontrolled
CTLA-4 Antigen
eng
uncontrolled
Programmed Cell Death 1 Receptor
eng
uncontrolled
B7-H1 Antigen
eng
uncontrolled
Drug Therapy, Combination
Medizin und Gesundheit
open_access
Klinik und Poliklinik für Dermatologie, Venerologie und Allergologie
Institut für diagnostische und interventionelle Neuroradiologie (ehem. Abteilung für Neuroradiologie)
Import
Förderzeitraum 2022
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/30461/jitc-10-e005930.pdf
29750
2022
eng
22
14
article
1
--
2022-11-11
--
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
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.
Cancers
2072-6694
10.3390/cancers14225543
urn:nbn:de:bvb:20-opus-297506
2022-12-15T14:05:36+00:00
sword
swordwue
attachment; filename=deposit.zip
11bb924ef9236a1d80e366a08fed6bf1
Cancers (2022) 14:22, 5543. https://doi.org/10.3390/cancers14225543
false
true
CC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International
Maximilian Haist
Henner Stege
Berenice Mareen Lang
Aikaterini Tsochataridou
Martin Salzmann
Peter Mohr
Dirk Schadendorf
Selma Ugurel
Jan-Malte Placke
Michael Weichenthal
Ralf Gutzmer
Ulrike Leiter
Martin Kaatz
Sebastian Haferkamp
Carola Berking
Markus Heppt
Barbara Tschechne
Patrick Schummer
Christoffer Gebhardt
Stephan Grabbe
Carmen Loquai
eng
uncontrolled
advanced cutaneous squamous cell carcinoma
eng
uncontrolled
checkpoint inhibitor therapy
eng
uncontrolled
cemiplimab
eng
uncontrolled
immunosuppression
eng
uncontrolled
response durability
eng
uncontrolled
real-world data
Medizin und Gesundheit
open_access
Klinik und Poliklinik für Dermatologie, Venerologie und Allergologie
Import
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/29750/cancers-14-05543-v2.pdf