Knispel, Sarah, Gassenmaier, Maximilian, Menzies, Alexander M., Loquai, Carmen, Johnson, Douglas B., Franklin, Cindy ORCID: 0000-0001-9142-5423, Gutzmer, Ralf, Hassel, Jessica C., Weishaupt, Carsten, Eigentler, Thomas, Schilling, Bastian, Schummer, Patrick, Sirokay, Judith ORCID: 0000-0003-3945-845X, Kiecker, Felix, Owen, Carina N., Fleischer, Maria, I, Cann, Christopher, Kaehler, Katharina C., Mohr, Peter, Bluhm, Leonie, Niebel, Dennis ORCID: 0000-0003-2069-0486, Thoms, Kai-Martin, Goldinger, Simone M., Reinhardt, Lydia, Meier, Friedegund, Berking, Carola, Reinhard, Raphael, Susok, Laura, Ascierto, Paolo A., Drexler, Konstantin, Pfoehler, Claudia, Tietze, Julia, Heinzerling, Lucie, Livingstone, Elisabeth, Ugurel, Selma, Long, Georgina, V, Stang, Andreas, Schadendorf, Dirk and Zimmer, Lisa ORCID: 0000-0002-3680-3521 (2021). Outcome of melanoma patients with elevated LDH treated with first-line targeted therapy or PD-1-based immune checkpoint inhibition. Eur. J. Cancer, 148. S. 61 - 76. OXFORD: ELSEVIER SCI LTD. ISSN 1879-0852

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Abstract

Background: Elevated lactate dehydrogenase (LDH) is a known predictive and prognostic factor for a poor outcome in patients with metastatic melanoma. It is unclear whether first-line targeted therapy (TT) or immune checkpoint inhibition (ICI) is more beneficial in melanoma patients with elevated LDH because prospective studies in this area are lacking. Methods: This multicentre retrospective cohort study was conducted at 25 melanoma centres worldwide to analyse progression-free survival (PFS) and overall survival (OS) among melanoma patients with elevated LDH. The role of confounders was addressed by using inverse probability of treatment weighting. Results: Among 173 BRAFV600-mutant patients, PFS at 12 months in the TT group was 22% compared with 52% in the combined anti-PD-1 and anti-CTLA-4 group (HR 0.6, 95% CI 0.4-1.0, p = 0.07) and 18% in the anti-PD-1 monotherapy group (HR 1.8, 95% CI 1.2-2.8, p = 0.003). Twelve months' OS was 48% in the TT group compared with 83% in the combined anti-PD-1 and anti-CTLA-4 group (HR 0.5, 95% CI 0.3-1.0, p = 0.03) and 50% in the anti-PD-1 monotherapy group (HR 1.2, 95% CI 0.8-2.0, p = 0.37). The ORR in the TT group was 63%, compared with 55% and 20% in the combined anti-PD-1 and anti-CTLA-4 and anti-PD-1 monotherapy group, respectively. Among 314 patients receiving ICI first-line, PFS at 12 months was 33% in the anti-PD-1 group versus 38% in the combined anti-PD-1 and anti-CTLA-4 group (HR 0.8, 95% CI 0.6-1.0; p = 0.07). OS at 12 months was 54% in the anti-PD-1 group versus 66% in the combined ICI group (HR 0.7, 95% CI 0.5-1.0; p = 0.03). The ORR was 30% in the anti-PD-1 monotherapy group and 43% in the combined anti-PD-1 and anti-CTLA-4 group. Results from multivariate analysis confirmed the absence of qualitative confounding. Conclusions: Among BRAF-mutant patients with elevated LDH, combined anti-PD-1 and anti-CTLA-4 blockade seems to be associated with prolonged OS compared with first-line TT. Among patients receiving ICI as a first-line treatment, OS appears to be longer for the combination of anti-PD-1 and anti-CTLA-4 than for anti-PD-1 alone. (C) 2021 Elsevier Ltd. All rights reserved.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Knispel, SarahUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Gassenmaier, MaximilianUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Menzies, Alexander M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Loquai, CarmenUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Johnson, Douglas B.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Franklin, CindyUNSPECIFIEDorcid.org/0000-0001-9142-5423UNSPECIFIED
Gutzmer, RalfUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hassel, Jessica C.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Weishaupt, CarstenUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Eigentler, ThomasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schilling, BastianUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schummer, PatrickUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Sirokay, JudithUNSPECIFIEDorcid.org/0000-0003-3945-845XUNSPECIFIED
Kiecker, FelixUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Owen, Carina N.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Fleischer, Maria, IUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Cann, ChristopherUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kaehler, Katharina C.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Mohr, PeterUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bluhm, LeonieUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Niebel, DennisUNSPECIFIEDorcid.org/0000-0003-2069-0486UNSPECIFIED
Thoms, Kai-MartinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Goldinger, Simone M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Reinhardt, LydiaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Meier, FriedegundUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Berking, CarolaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Reinhard, RaphaelUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Susok, LauraUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ascierto, Paolo A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Drexler, KonstantinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Pfoehler, ClaudiaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Tietze, JuliaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Heinzerling, LucieUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Livingstone, ElisabethUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ugurel, SelmaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Long, Georgina, VUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Stang, AndreasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schadendorf, DirkUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Zimmer, LisaUNSPECIFIEDorcid.org/0000-0002-3680-3521UNSPECIFIED
URN: urn:nbn:de:hbz:38-606780
DOI: 10.1016/j.ejca.2021.01.034
Journal or Publication Title: Eur. J. Cancer
Volume: 148
Page Range: S. 61 - 76
Date: 2021
Publisher: ELSEVIER SCI LTD
Place of Publication: OXFORD
ISSN: 1879-0852
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
DOUBLE-BLIND; IPILIMUMAB; NIVOLUMAB; MONOTHERAPY; DABRAFENIB; SURVIVAL; VEMURAFENIB; COBIMETINIB; TRAMETINIB; PLACEBOMultiple languages
OncologyMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/60678

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