First-line therapy-stratified survival in BRAF-mutant melanoma: a retrospective multicenter analysis

Background Inhibition of the mitogen-activated protein kinase (MAPK) pathway as well as programmed death 1 receptor (PD-1) blockade was shown to prolong overall survival (OS) in patients with advanced B-Raf proto-oncogene (BRAF)-mutant melanoma. However, due to the lack of head-to-head trials, it re...

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Bibliographic Details
Published in:Cancer Immunology, Immunotherapy Immunotherapy, 2019-05, Vol.68 (5), p.765-772
Main Authors: Schilling, Bastian, Martens, Alexander, Geukes Foppen, Marnix H., Gebhardt, Christoffer, Hassel, Jessica C., Rozeman, Elisa A., Gesierich, Anja, Gutzmer, Ralf, Kähler, Katharina C., Livingstone, Elisabeth, Diamantopoulos, Panagiotis T., Gogas, Helen, Madonna, Gabriele, Ascierto, Paolo A., Goldinger, Simone M., Mangana, Johanna, Garbe, Claus, Schadendorf, Dirk, Blank, Christian, Weide, Benjamin
Format: Article
Language:English
Subjects:
Antibodies, Monoclonal, Humanized - therapeutic use
Antineoplastic Combined Chemotherapy Protocols - therapeutic use
Blocking antibodies
Cancer Research
Clinical trials
Cohort Studies
Extracellular signal-regulated kinase
Extracellular Signal-Regulated MAP Kinases - antagonists & inhibitors
Humans
Immunology
Kinases
L-Lactate dehydrogenase
Lactic acid
MAP kinase
Medicine
Medicine & Public Health
MEK inhibitors
Melanoma
Melanoma - drug therapy
Melanoma - mortality
Metastases
Metastasis
Neoplasm Metastasis
Nivolumab - therapeutic use
Oncology
Original
Original Article
Patients
PD-1 protein
Programmed Cell Death 1 Receptor - immunology
Protein kinase
Protein Kinase Inhibitors - therapeutic use
Proto-Oncogene Mas
Proto-Oncogene Proteins B-raf - antagonists & inhibitors
Proto-Oncogene Proteins B-raf - genetics
Retrospective Studies
Signal Transduction
Skin Neoplasms - drug therapy
Skin Neoplasms - mortality
Survival
Survival Analysis
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Summary:Background Inhibition of the mitogen-activated protein kinase (MAPK) pathway as well as programmed death 1 receptor (PD-1) blockade was shown to prolong overall survival (OS) in patients with advanced B-Raf proto-oncogene (BRAF)-mutant melanoma. However, due to the lack of head-to-head trials, it remains unclear if one of these therapeutic approaches should be preferred in first-line therapy. Here, we present a retrospective analysis comparing anti-PD-1 monotherapy with BRAF/MAPK/ERK kinase (MEK) combined inhibition used as first-line agents in a real-world clinical setting. Patients and methods Clinical data, routine blood counts and lactate dehydrogenase (LDH) levels of 301 patients with unresectable or metastatic melanoma harboring an activating mutation in BRAF (V600E/K) were included. Of these, 106 received anti-PD-1 antibodies, while 195 patients were treated with a selective BRAF inhibitor combined with an MEK inhibitor as palliative first-line therapy. Patients were sub-grouped according to previously described predictive and prognostic markers. Results OS was significantly longer in patients receiving anti-PD-1 monotherapy compared to patients receiving combined MAPK inhibitors. Subsequent therapies were comparable among these groups. The difference in OS was less pronounced in patients with high LDH levels and visceral metastatic spread. Conclusion First-line treatment with a PD-1 blocking antibody might be associated with longer OS than first-line inhibition of the MAPK pathway in patients with advanced melanoma harboring mutant BRAF. These hypothesis-generating data need to be confirmed or rejected in prospective, randomized trials.
ISSN:0340-7004
1432-0851
DOI:10.1007/s00262-019-02311-1