PMID- 36428636
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20230308
IS  - 2072-6694 (Print)
IS  - 2072-6694 (Electronic)
IS  - 2072-6694 (Linking)
VI  - 14
IP  - 22
DP  - 2022 Nov 11
TI  - 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.
LID - 10.3390/cancers14225543 [doi]
LID - 5543
AB  - 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.
FAU - Haist, Maximilian
AU  - Haist M
AUID- ORCID: 0000-0002-6720-7570
AD  - Department of Dermatology, University Medical Center Mainz, 55131 Mainz, Germany.
AD  - Department of Pathology, Stanford University School of Medicine, Stanford, CA 
      94305, USA.
AD  - Department of Microbiology & Immunology, Stanford University School of Medicine, 
      Stanford, CA 94305, USA.
FAU - Stege, Henner
AU  - Stege H
AD  - Department of Dermatology, University Medical Center Mainz, 55131 Mainz, Germany.
FAU - Lang, Berenice Mareen
AU  - Lang BM
AD  - Department of Dermatology, University Medical Center Mainz, 55131 Mainz, Germany.
FAU - Tsochataridou, Aikaterini
AU  - Tsochataridou A
AD  - Department of Dermatology, University Medical Center Mainz, 55131 Mainz, Germany.
FAU - Salzmann, Martin
AU  - Salzmann M
AUID- ORCID: 0000-0003-4310-4822
AD  - Department of Dermatology and National Center for Tumor Diseases, University 
      Hospital Heidelberg, 69120 Heidelberg, Germany.
FAU - Mohr, Peter
AU  - Mohr P
AD  - Department of Dermatology, Elbe Kliniken Buxtehude, 21614 Buxtehude, Germany.
FAU - Schadendorf, Dirk
AU  - Schadendorf D
AD  - Department of Dermatology, University Hospital Essen, 45122 Essen, Germany.
FAU - Ugurel, Selma
AU  - Ugurel S
AUID- ORCID: 0000-0002-9384-6704
AD  - Department of Dermatology, University Hospital Essen, 45122 Essen, Germany.
FAU - Placke, Jan-Malte
AU  - Placke JM
AD  - Department of Dermatology, University Hospital Essen, 45122 Essen, Germany.
FAU - Weichenthal, Michael
AU  - Weichenthal M
AUID- ORCID: 0000-0002-9060-4961
AD  - Department of Dermatology, Campus Kiel, University Hospital of Schleswig-Holstein 
      Hospital, 24105 Kiel, Germany.
FAU - Gutzmer, Ralf
AU  - Gutzmer R
AUID- ORCID: 0000-0001-7921-2820
AD  - Department of Dermatology and Allergy, Skin Cancer Center Hannover, 30625 
      Hannover, Germany.
FAU - Leiter, Ulrike
AU  - Leiter U
AUID- ORCID: 0000-0002-8019-1577
AD  - Center of Dermatooncology, Department of Dermatology, Eberhard-Karls-University, 
      72076 Tuebingen, Germany.
FAU - Kaatz, Martin
AU  - Kaatz M
AD  - Department of Dermatology, Wald-Klinikum Gera, 07548 Gera, Germany.
FAU - Haferkamp, Sebastian
AU  - Haferkamp S
AUID- ORCID: 0000-0002-3894-8345
AD  - Department of Dermatology, University Hospital Regensburg, 93053 Regensburg, 
      Germany.
FAU - Berking, Carola
AU  - Berking C
AD  - Department of Dermatology, Uniklinikum Erlangen, CCC Erlangen-EMN, 
      Friedrich-Alexander University Erlangen-Nurnberg, 91054 Erlangen, Germany.
FAU - Heppt, Markus
AU  - Heppt M
AUID- ORCID: 0000-0003-4603-1825
AD  - Department of Dermatology, Uniklinikum Erlangen, CCC Erlangen-EMN, 
      Friedrich-Alexander University Erlangen-Nurnberg, 91054 Erlangen, Germany.
FAU - Tschechne, Barbara
AU  - Tschechne B
AD  - KRH Klinikum Neustadt am Rubenberge, Specialist for Internal Medicine Hematology 
      and Oncology, 31535 Neustadt, Germany.
FAU - Schummer, Patrick
AU  - Schummer P
AD  - Department of Dermatology, University Hospital Wurzburg, 97080 Wurzburg, Germany.
FAU - Gebhardt, Christoffer
AU  - Gebhardt C
AUID- ORCID: 0000-0001-7090-9584
AD  - Skin Cancer Center, Department of Dermatology and Venereology, University 
      Hospital Hamburg-Eppendorf (UKE), 20246 Hamburg, Germany.
FAU - Grabbe, Stephan
AU  - Grabbe S
AUID- ORCID: 0000-0002-6863-8719
AD  - Department of Dermatology, University Medical Center Mainz, 55131 Mainz, Germany.
FAU - Loquai, Carmen
AU  - Loquai C
AD  - Department of Dermatology, University Medical Center Mainz, 55131 Mainz, Germany.
AD  - Department of Dermatology, Gesundheit-Nord Hospital Bremen, 28102 Bremen, 
      Germany.
LA  - eng
GR  - Project number: HA 9793/1-1/Deutsche Forschungsgemeinschaft/
GR  - Intramural research funding/University Medical Center Mainz/
PT  - Journal Article
DEP - 20221111
PL  - Switzerland
TA  - Cancers (Basel)
JT  - Cancers
JID - 101526829
PMC - PMC9688854
OTO - NOTNLM
OT  - advanced cutaneous squamous cell carcinoma
OT  - cemiplimab
OT  - checkpoint inhibitor therapy
OT  - immunosuppression
OT  - real-world data
OT  - response durability
COIS- H.S., M.H., M.K., J.-M.P., and B.T. declare no conflict of interest. A.T. 
      declares travel support from Novartis. B.M.L. declares honoraria and travel 
      assistance from Novartis, Sanofi, and MSD. M.S. declares honoraria and/or travel 
      grants from Abbvie, Bristol-Myers Squibb (BMS), Merck, Merck Sharp & Dohme (MSD), 
      Novartis, Pfizer, and Sanofi. D.S. declares research support from Bristol-Myers 
      Squibb, Novartis, and Amgen; speaker and advisory board honoraria from Array, 
      Bristol-Myers Squibb, Helsinn, Merck Sharp & Dohme, Merck Serono, Immunocore, 
      InFlarX, Nektar, Neracare, Novartis, OncoSec, Pfizer, Philogen, Pierre-Fabre, 
      Replimune, Roche, Sandoz, Sanofi, and Sun Pharma; travel support from 
      Bristol-Myers Squibb, Merck Sharp & Dohme, Merck-Serono, Nektar, Novartis, 
      Pierre-Fabre, Roche, and Sanofi. S.U. declares research support from Bristol 
      Myers Squibb and Merck Serono; speakers and advisory board honoraria from Bristol 
      Myers Squibb, Merck Sharp & Dohme, Merck Serono, Novartis, and Roche; travel 
      support from Bristol Myers Squibb, Merck Sharp & Dohme, and Pierre Fabre, outside 
      the submitted work. J.-M.P served as consultant and/or has received honoraria 
      from Bristol-Myers Squibb and Novartis, and has received travel support from 
      Bristol-Myers Squibb, Novartis and Therakos. P.M. declares research support from 
      Bristol-Myers Squibb and Merck Sharp & Dohme; speaker and advisory board 
      honoraria from Bristol-Myers Squibb, Merck Sharp & Dohme, Roche/Genentech, 
      Novartis, Amgen, GlaxoSmithKline, Pierre Fabre, Merck, Sanofi, Beiersdorf, and 
      Sun Pharma; travel support from Bristol-Myers Squibb, Merck Sharp & Dohme, 
      Novartis, Pierre Fabre, Amgen, and Roche; consulting or advisory role: 
      Bristol-Myers Squibb, Merck Sharp & Dohme, Novartis, Amgen, Roche, 
      GlaxoSmithKline, Merck, Pierre Fabre, Beiersdorf Immunocore, and Sanofi. M.W. 
      declares speaker and advisory board honoraria from Merck, Bristol-Myers Squibb, 
      Roche, Novartis, Sanofi, Pierre Fabre, Beiersdorf, Sun Pharma, and Takeda. S.H. 
      declares research support from Bristol-Myers Squibb; speaker and advisory board 
      honoraria from Bristol-Myers Squibb, Merck Sharp & Dohme, Novartis, Amgen, Pierre 
      Fabre, and Sanofi. R.G. declares research support from Pfizer, Johnson&Johnson, 
      Novartis, Amgen, Sanofi, Merck-Serono, and Kyowa-Kirin; honoraria for lectures 
      from Roche Pharma, Bristol-MyersSquibb, Novartis, MSD, Almirall-Hermal, Amgen, 
      Merck-Serono, Bayer, 4SC, SUN, Pierre-Fabre, and Sanofi; advisory honoraria from 
      Roche Pharma, Bristol-MyersSquibb, Novartis, MSD, Almirall-Hermal, Amgen, 
      Pierre-Fabre, Merck-Serono, 4SC, SUN, Merck-Serono, Sanofi, and Immunocore. P.S. 
      declares honoraria from Bristol-Myers Squibb; an institutional research grant 
      from Novartis; travel support from Bristol-Myers Squibb, Lilly, Sanofi-Aventis, 
      Novartis, Pierre Fabre Pharmaceuticals, and Sun Pharmaceuticals. M.V.H. declares 
      honoraria from MSD, BMS, Roche, Novartis, Sun Pharma, Sanofi, Almirall, 
      Biofrontera, and Galderma. C.B. declares honoraria from Almirall, BMS, 
      Immunocore, Leo Pharma, MSD, Novartis, Roche, Pierre Fabre, and Sanofi. C.G. is a 
      member of the advisory board of, and has received honoraria and travel expenses 
      by, Almirall, Amgen, Beiersdorf, BioNTech, Bristol-Myers Squibb, Immunocore, 
      Janssen, MSD Sharp & Dohme, Novartis, Pierre-Fabre, Roche, Sanofi Genzyme, SUN 
      Pharma, and Sysmex/Inostics. U.L declares research support from MSD; honoraria 
      from Roche, Novartis, Sanofi, MSD, and Sun Pharma; advisory honoraria from Roche, 
      Sanofi, MSD, Novartis, Sun Pharma, and Almirall Hermal. S.G. declares honoraria 
      for advisory boards, oral presentations, and travel expenses from Roche, 
      Novartis, MSD, and BMS outside the submitted work. C.L. declares speakers, 
      advisory board honoraria, and travel support from Bristol Myers Squibb, Merck 
      Sharp and Dohme, Merck Serono, Novartis, Roche, Pierre Fabre, Sun Pharma, Kiowa 
      Kirin, Sanofi, Biontech, and Almirall Hermal outside the submitted work.
EDAT- 2022/11/27 06:00
MHDA- 2022/11/27 06:01
PMCR- 2022/11/11
CRDT- 2022/11/26 01:04
PHST- 2022/10/26 00:00 [received]
PHST- 2022/11/08 00:00 [revised]
PHST- 2022/11/09 00:00 [accepted]
PHST- 2022/11/26 01:04 [entrez]
PHST- 2022/11/27 06:00 [pubmed]
PHST- 2022/11/27 06:01 [medline]
PHST- 2022/11/11 00:00 [pmc-release]
AID - cancers14225543 [pii]
AID - cancers-14-05543 [pii]
AID - 10.3390/cancers14225543 [doi]
PST - epublish
SO  - Cancers (Basel). 2022 Nov 11;14(22):5543. doi: 10.3390/cancers14225543.