Randomised phase II study of second-line olaratumab with mitoxantrone/prednisone versus mitoxantrone/prednisone alone in metastatic castration-resistant prostate cancer
Jazyk angličtina Země Anglie, Velká Británie Médium print-electronic
Typ dokumentu klinické zkoušky, fáze II, srovnávací studie, časopisecké články, multicentrická studie, randomizované kontrolované studie, práce podpořená grantem
PubMed
30573277
DOI
10.1016/j.ejca.2018.10.005
PII: S0959-8049(18)31433-3
Knihovny.cz E-zdroje
- Klíčová slova
- Antineoplastics, Metastatic, Mitoxantrone, Monoclonal antibodies, Olaratumab, Platelet-derived growth factor alpha, Prostate cancer, Receptor,
- MeSH
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- metastázy nádorů MeSH
- míra přežití MeSH
- mitoxantron aplikace a dávkování MeSH
- monoklonální protilátky aplikace a dávkování MeSH
- nádory prostaty rezistentní na kastraci farmakoterapie patologie MeSH
- následné studie MeSH
- prednison aplikace a dávkování MeSH
- prognóza MeSH
- protokoly protinádorové kombinované chemoterapie terapeutické užití MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- Publikační typ
- časopisecké články MeSH
- klinické zkoušky, fáze II MeSH
- multicentrická studie MeSH
- práce podpořená grantem MeSH
- randomizované kontrolované studie MeSH
- srovnávací studie MeSH
- Názvy látek
- mitoxantron MeSH
- monoklonální protilátky MeSH
- olaratumab MeSH Prohlížeč
- prednison MeSH
INTRODUCTION: Platelet-derived growth factor receptor-α (PDGFRα) is expressed in primary prostate adenocarcinoma and in associated skeletal metastases. Olaratumab is a fully human monoclonal antibody that binds PDGFRα 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/m2, 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.
Centrum Onkologii Instytut im Marii Sklodowskiej Curie Warsaw Poland
CHU Sart Tilman University of Liège Liège Belgium
Clinica Universidad De Navarra Pamplona Spain
Department of Urologie Universitätsmedizin Rostock Rostock Germany
Department of Urology and Uro Oncology University Hospital Cologne Cologne Germany
Department of Urology Josa Andras Teaching Hospital Nyiregyhaza Hungary
Department of Urology University of Freiburg Freiburg Germany
Eli Lilly and Company Basingstoke United Kingdom
Eli Lilly and Company Bridgewater NJ USA
Eli Lilly and Company Indianapolis IN USA
Medical Oncology Department Hospital 12 De Octubre Madrid Spain
Medical Oncology Department Santa Chiara Hospital Trento Italy
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