Universität zu Köln

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:	Creators Email ORCID ORCID Put Code Hakenberg, Oliver W. UNSPECIFIED UNSPECIFIED UNSPECIFIED Perez-Gracia, Jose Luis UNSPECIFIED orcid.org/0000-0003-4941-9075 UNSPECIFIED Castellano, Daniel UNSPECIFIED UNSPECIFIED UNSPECIFIED Demkow, Tomasz UNSPECIFIED UNSPECIFIED UNSPECIFIED Ali, Tarek UNSPECIFIED UNSPECIFIED UNSPECIFIED Caffo, Orazio UNSPECIFIED UNSPECIFIED UNSPECIFIED Heidenreich, Axel UNSPECIFIED UNSPECIFIED UNSPECIFIED Schultze-Seemann, Wolfgang UNSPECIFIED UNSPECIFIED UNSPECIFIED Sautois, Brieuc UNSPECIFIED UNSPECIFIED UNSPECIFIED Pavlik, Ivan UNSPECIFIED UNSPECIFIED UNSPECIFIED Qin, Amy UNSPECIFIED UNSPECIFIED UNSPECIFIED Novosiadly, Ruslan D. UNSPECIFIED UNSPECIFIED UNSPECIFIED Shahir, Ashwin UNSPECIFIED UNSPECIFIED UNSPECIFIED Ilaria, Robert, Jr. UNSPECIFIED UNSPECIFIED UNSPECIFIED Nippgen, Johannes UNSPECIFIED UNSPECIFIED UNSPECIFIED
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:	Keywords Language GROWTH-FACTOR RECEPTOR; SYSTEMIC THERAPY; PLUS PREDNISONE; MEN; BIOMARKER; SURVIVAL Multiple languages Oncology Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/14033