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Randomised phase II study of second-line olaratumab with mitoxantrone/prednisone versus mitoxantrone/prednisone alone in metastatic castration-resistant prostate cancer

OW. Hakenberg, JL. Perez-Gracia, D. Castellano, T. Demkow, T. Ali, O. Caffo, A. Heidenreich, W. Schultze-Seemann, B. Sautois, I. Pavlik, A. Qin, RD. Novosiadly, A. Shahir, R. Ilaria, J. Nippgen,

. 2019 ; 107 (-) : 186-195. [pub] 20181217

Jazyk angličtina Země Velká Británie

Typ dokumentu klinické zkoušky, fáze II, srovnávací studie, časopisecké články, multicentrická studie, randomizované kontrolované studie, práce podpořená grantem

Perzistentní odkaz   https://www.medvik.cz/link/bmc20022933

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.

Citace poskytuje Crossref.org

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$a INTRODUCTION: Platelet-derived growth factor receptor-α (PDGFRα) is expressed in primary prostate adenocarcinoma and in associated skeletal metastases. Olaratumab is a fully human monoclonal antibody that binds PDGFRα and blocks downstream signalling. This phase II study assessed the efficacy and safety of olaratumab in combination with mitoxantrone and prednisone (M/P) versus M/P alone in patients with metastatic castration-resistant prostate cancer (mCRPC) who progressed after docetaxel. METHODS: Patients were randomised to receive 21-d cycles of olaratumab (15 mg/kg, Days 1 and 8) plus mitoxantrone (12 mg/m2, Day 1) and prednisone (5 mg, twice daily) or M/P alone. Progression-free survival (PFS) was the primary end-point. Secondary end-points included overall survival (OS), safety, and circulating tumour cell (CTC) counts. RESULTS: A total of 123 patients were randomised, 63 to olaratumab + M/P and 60 to M/P. Median PFS was 2.3 months for olaratumab + M/P and 2.4 months for M/P (hazard ratio [HR] = 1.29; 95% confidence interval [CI] = 0.87-1.90). Median OS was 14.2 months for olaratumab + M/P and 12.8 months for M/P (HR = 1.08; 95% CI = 0.72-1.61). Both treatment arms had similar toxicity profiles; neutropenia (24% versus 15%), anaemia (13% versus 14%) and fatigue (11% versus 9%) (olaratumab + M/P versus M/P, respectively) were the most common grade ≥3 events. High CTC count was associated with poorer OS in both arms. Patients with very high cell counts (>37 cells/7.5 ml) exhibited improved OS with olaratumab + M/P (interaction P = 0.043). CONCLUSIONS: Olaratumab + M/P had an acceptable safety profile but did not improve the efficacy of M/P chemotherapy. Further study with selected patient populations and earlier in the disease course might be considered.
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$a Perez-Gracia, Jose Luis $u Clinica Universidad De Navarra, Pamplona, Spain. Electronic address: jlgracia@unav.es.
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$a Castellano, Daniel $u Medical Oncology Department (CiberOnc), Hospital 12 De Octubre, Madrid, Spain. Electronic address: cdanicas@hotmail.com.
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$a Demkow, Tomasz $u Centrum Onkologii - Instytut im. Marii Sklodowskiej-Curie, Warsaw, Poland. Electronic address: demkow@coi.waw.pl.
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$a Ali, Tarek $u Department of Urology, Josa Andras Teaching Hospital, Nyiregyhaza, Hungary. Electronic address: tarekali@freemail.hu.
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$a Caffo, Orazio $u Medical Oncology Department, Santa Chiara Hospital, Trento, Italy. Electronic address: orazio.caffo@apss.tn.it.
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$a Heidenreich, Axel $u Department of Urology and Uro-Oncology, University Hospital Cologne, Cologne, Germany. Electronic address: axel.heidenreich@uk-koeln.de.
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$a Schultze-Seemann, Wolfgang $u Department of Urology, University of Freiburg, Freiburg, Germany. Electronic address: wolfgang.schultze-seemann@uniklinik-freiburg.de.
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$a Sautois, Brieuc $u CHU Sart Tilman, University of Liège, Liège, Belgium. Electronic address: brieuc.sautois@chu.ulg.ac.be.
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$a Pavlik, Ivan $u Department of Urology, General University Hospital, And First Faculty of Medicine, Charles University, Prague, Czech Republic. Electronic address: ivan.pavlik@vfn.cz.
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$a Qin, Amy $u Eli Lilly and Company, Bridgewater, NJ, USA. Electronic address: aqin@dsi.com.
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$a Novosiadly, Ruslan D $u Eli Lilly and Company, NY, USA. Electronic address: ruslan.novosiadly@lilly.com.
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$a Shahir, Ashwin $u Eli Lilly and Company, Basingstoke, United Kingdom. Electronic address: shahir_ashwin@lilly.com.
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$a Nippgen, Johannes $u Eli Lilly and Company, Bridgewater, NJ, USA. Electronic address: dr.nippgen@web.de.
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