Koch, Elias A. T., Petzold, Anne, Wessely, Anja ORCID: 0000-0003-1940-5115, Dippel, Edgar, Gesierich, Anja, Gutzmer, Ralf, Hassel, Jessica C., Haferkamp, Sebastian ORCID: 0000-0002-3894-8345, Hohberger, Bettina, Kaehler, Katharina C., Knorr, Harald, Kreuzberg, Nicole, Leiter, Ulrike, Loquai, Carmen, Meier, Friedegund, Meissner, Markus, Mohr, Peter, Pfoehler, Claudia, Rahimi, Farnaz, Schadendorf, Dirk, Schell, Beatrice, Schlaak, Max, Terheyden, Patrick, Thoms, Kai-Martin, Schuler-Thurner, Beatrice, Ugurel, Selma, Ulrich, Jens, Utikal, Jochen, Weichenthal, Michael, Ziller, Fabian, Berking, Carola and Heppt, Markus V. (2021). Immune Checkpoint Blockade for Metastatic Uveal Melanoma: Patterns of Response and Survival According to the Presence of Hepatic and Extrahepatic Metastasis. Cancers, 13 (13). BASEL: MDPI. ISSN 2072-6694

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Abstract

Simple Summary This retrospective multicenter study examines the influence of hepatic and extrahepatic metastases on the response of immune checkpoint blockade (ICB) in patients with metastatic uveal melanoma. A better response to dual ICB was observed in the presence of extrahepatic metastases in two recently published phase II trials. Therefore, we investigated two cohorts with and without extrahepatic metastasis and have assembled a population of 178 patients treated with ICB. The survival of this large cohort of patients with advanced UM was more favorable than that 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. 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, chi(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.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Koch, Elias A. T.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Petzold, AnneUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wessely, AnjaUNSPECIFIEDorcid.org/0000-0003-1940-5115UNSPECIFIED
Dippel, EdgarUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Gesierich, AnjaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Gutzmer, RalfUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hassel, Jessica C.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Haferkamp, SebastianUNSPECIFIEDorcid.org/0000-0002-3894-8345UNSPECIFIED
Hohberger, BettinaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kaehler, Katharina C.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Knorr, HaraldUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kreuzberg, NicoleUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Leiter, UlrikeUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Loquai, CarmenUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Meier, FriedegundUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Meissner, MarkusUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Mohr, PeterUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Pfoehler, ClaudiaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Rahimi, FarnazUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schadendorf, DirkUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schell, BeatriceUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schlaak, MaxUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Terheyden, PatrickUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Thoms, Kai-MartinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schuler-Thurner, BeatriceUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ugurel, SelmaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ulrich, JensUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Utikal, JochenUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Weichenthal, MichaelUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ziller, FabianUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Berking, CarolaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Heppt, Markus V.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-606616
DOI: 10.3390/cancers13133359
Journal or Publication Title: Cancers
Volume: 13
Number: 13
Date: 2021
Publisher: MDPI
Place of Publication: BASEL
ISSN: 2072-6694
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
OncologyMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/60661

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