Hakenberg, Oliver W., Perez-Gracia, Jose Luis ORCID: 0000-0003-4941-9075, Castellano, Daniel, Demkow, Tomasz, Ali, Tarek, Caffo, Orazio, Heidenreich, Axel, Schultze-Seemann, Wolfgang, Sautois, Brieuc, Pavlik, Ivan, Qin, Amy, Novosiadly, Ruslan D., Shahir, Ashwin, Ilaria, Robert, Jr. and Nippgen, Johannes (2019). Randomised phase II study of second-line olaratumab with mitoxantrone/prednisone versus mitoxantrone/prednisone alone in metastatic castration-resistant prostate cancer. Eur. J. Cancer, 107. S. 186 - 196. OXFORD: ELSEVIER SCI LTD. ISSN 1879-0852

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Abstract

Introduction: Platelet-derived growth factor receptor-alpha (PDGFR alpha) is expressed in primary prostate adenocarcinoma and in associated skeletal metastases. Olaratumab is a fully human monoclonal antibody that binds PDGFR alpha and blocks downstream signalling. This phase II study assessed the efficacy and safety of olaratumab in combination with mitoxantrone and prednisone (M/P) versus M/P alone in patients with metastatic castration-resistant prostate cancer (mCRPC) who progressed after docetaxel. Methods: Patients were randomised to receive 21-d cycles of olaratumab (15 mg/kg, Days 1 and 8) plus mitoxantrone (12 mg/m(2), Day 1) and prednisone (5 mg, twice daily) or M/P alone. Progression-free survival (PFS) was the primary end-point. Secondary end-points included overall survival (OS), safety, and circulating tumour cell (CTC) counts. Results: A total of 123 patients were randomised, 63 to olaratumab + M/P and 60 to M/P. Median PFS was 2.3 months for olaratumab + M/P and 2.4 months for M/P (hazard ratio [HR] = 1.29; 95% confidence interval [CI] = 0.87-1.90). Median OS was 14.2 months for olaratumab + M/P and 12.8 months for M/P (HR = 1.08; 95% CI = 0.72-1.61). Both treatment arms had similar toxicity profiles; neutropenia (24% versus 15%), anaemia (13% versus 14%) and fatigue (11% versus 9%) (olaratumab + M/P versus M/P, respectively) were the most common grade >= 3 events. High CTC count was associated with poorer OS in both arms. Patients with very high cell counts (>37 cells/7.5 ml) exhibited improved OS with olaratumab + M/P (interaction P = 0.043). Conclusions: Olaratumab + M/P had an acceptable safety profile but did not improve the efficacy of M/P chemotherapy. Further study with selected patient populations and earlier in the disease course might be considered. (C) 2018 Published by Elsevier Ltd.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Hakenberg, Oliver W.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Perez-Gracia, Jose LuisUNSPECIFIEDorcid.org/0000-0003-4941-9075UNSPECIFIED
Castellano, DanielUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Demkow, TomaszUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ali, TarekUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Caffo, OrazioUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Heidenreich, AxelUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schultze-Seemann, WolfgangUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Sautois, BrieucUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Pavlik, IvanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Qin, AmyUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Novosiadly, Ruslan D.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Shahir, AshwinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ilaria, Robert, Jr.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Nippgen, JohannesUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-140331
DOI: 10.1016/j.ejca.2018.10.005
Journal or Publication Title: Eur. J. Cancer
Volume: 107
Page Range: S. 186 - 196
Date: 2019
Publisher: ELSEVIER SCI LTD
Place of Publication: OXFORD
ISSN: 1879-0852
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
GROWTH-FACTOR RECEPTOR; SYSTEMIC THERAPY; PLUS PREDNISONE; MEN; BIOMARKER; SURVIVALMultiple languages
OncologyMultiple languages
Refereed: Yes
URI: http://kups.ub.uni-koeln.de/id/eprint/14033

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