Knispel, Sarah and Gassenmaier, Maximilian and Menzies, Alexander M. and Loquai, Carmen and Johnson, Douglas B. and Franklin, Cindy and Gutzmer, Ralf and Hassel, Jessica C. and Weishaupt, Carsten and Eigentler, Thomas and Schilling, Bastian and Schummer, Patrick and Sirokay, Judith and Kiecker, Felix and Owen, Carina N. and Fleischer, Maria and Cann, Christopher and Kaehler, Katharina C. and Mohr, Peter and Bluhm, Leonie and Niebel, Dennis and Thoms, Kai-Martin and Goldinger, Simone M. and Reinhardt, Lydia and Meier, Friedegund and Berking, Carola and Reinhard, Raphael and Susok, Laura and Ascierto, Paolo A. and Drexler, Konstantin and Pfoehler, Claudia and Tietze, Julia and Heinzerling, Lucie and Livingstone, Elisabeth and Ugurel, Selma and Long, Georgina and Stang, Andreas and Schadendorf, Dirk and Zimmer, Lisa (2021) Outcome of melanoma patients with elevated LDH treated with first-line targeted therapy or PD-1-based immune checkpoint inhibition. EUROPEAN JOURNAL OF CANCER, 148. pp. 61-75. ISSN 0959-8049, 1879-0852
Full text not available from this repository. (Request a copy)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: | Article |
|---|---|
| Uncontrolled Keywords: | DOUBLE-BLIND; IPILIMUMAB; NIVOLUMAB; MONOTHERAPY; DABRAFENIB; SURVIVAL; VEMURAFENIB; COBIMETINIB; TRAMETINIB; PLACEBO; Melanoma; Immune checkpoint inhibition; PD-1; CTLA-4; Targeted therapy; LDH; Response; Progression; Survival |
| Divisions: | Medicine > Lehrstuhl für Dermatologie und Venerologie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 30 Sep 2022 14:08 |
| Last Modified: | 30 Sep 2022 14:08 |
| URI: | https://pred.uni-regensburg.de/id/eprint/48157 |
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