Pretreatment metastatic growth rate determines clinical outcome of advanced melanoma patients treated with anti-PD-1 antibodies: a multicenter cohort study
| Autor: | Ramon Stäger, Suzan Stürmer, Carola Berking, Philipp Gussek, Fiona André, Amadeus Schraag, Chiara Ebel, Max M Lenders, Lydia Reinhardt, Lukas Flatz, Stefan Diem, Roland Lang, Martin Röcken, Susanne Kimeswenger, Mirjana Ziemer, Georg Richtig, Milena Dudda, Ulrike Leiter, J. Mangana, Bernhard Klumpp, Thomas Eigentler, Christoffer Gebhardt, Michael Paar, Claus Garbe, Van Anh Nguyen, Benjamin Weide, Patrick Terheyden, Maximilian Gassenmaier, Antonio Cozzio, Andrea Forschner, Friedegund Meier, Wolfram Hoetzenecker, Carmen Loquai, Angela Oellinger, Kathrin Kühl, Caroline Zellweger, Nikolaus B. Wagner, Erika Richtig, Natalie Ring |
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| Rok vydání: | 2020 |
| Předmět: |
Male
0301 basic medicine Oncology Cancer Research Skin Neoplasms Time Factors Programmed Cell Death 1 Receptor Pembrolizumab Metastasis 0302 clinical medicine Risk Factors Immunotherapy Biomarkers Immunology and Allergy Immune Checkpoint Inhibitors RC254-282 Melanoma Neoplasms. Tumors. Oncology. Including cancer and carcinogens Middle Aged ddc Europe Nivolumab Treatment Outcome 030220 oncology & carcinogenesis Cohort Molecular Medicine Female immunotherapy Cohort study tumor medicine.medical_specialty Immunology Antibodies Monoclonal Humanized Risk Assessment 03 medical and health sciences Predictive Value of Tests Internal medicine melanoma medicine Humans Cell Proliferation Neoplasm Staging Retrospective Studies Pharmacology Proportional hazards model business.industry biomarkers Reproducibility of Results medicine.disease 030104 developmental biology Tomography X-Ray Computed business Brain metastasis |
| Zdroj: | Journal for ImmunoTherapy of Cancer, Vol 9, Iss 5 (2021) Journal for Immunotherapy of Cancer |
| Popis: | BackgroundCheckpoint inhibitors revolutionized the treatment of metastatic melanoma patients. Although tumor burden and lactate dehydrogenase (LDH) are associated with overall survival (OS), the impact of tumor growth kinetics remains elusive and in part contradictory. The aims of this study were to develop a novel simple and rapid method that estimates pretreatment metastatic growth rate (MGR) and to investigate its prognostic impact in melanoma patients treated with antiprogrammed death receptor-1 (PD-1) antibodies.MethodsMGR was assessed in three independent cohorts of a total of 337 unselected consecutive metastasized stage IIIB–IV melanoma patients (discovery cohort: n=53, confirmation cohort: n=126, independent multicenter validation cohort: n=158). MGR was computed during the pretreatment period before initiation of therapy with anti-PD-1 antibodies nivolumab or pembrolizumab by measuring the increase of the longest diameter of the largest target lesion. Tumor doubling time served as quality control. Kaplan-Meier analysis and univariable as well as multivariable Cox regression were used to examine the prognostic impact of MGR.ResultsPretreatment MGR >3.9 mm/month was associated with impaired OS in the discovery cohort (HR 6.19, 95% CI 2.92 to 13.10, pConclusionsHigh pretreatment MGR is an independent strong prognostic biomarker associated with unfavorable survival of melanoma patients receiving anti-PD-1 antibodies. Further investigations are warranted to assess the predictive impact of MGR in distinct systemic therapeutic regimens. |
| Databáze: | OpenAIRE |
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