Oliver W Hakenberg1, Jose Luis Perez-Gracia2, Daniel Castellano3, Tomasz Demkow4, Tarek Ali5, Orazio Caffo6, Axel Heidenreich7, Wolfgang Schultze-Seemann8, Brieuc Sautois9, Ivan Pavlik10, Amy Qin11, Ruslan D Novosiadly12, Ashwin Shahir13, Robert Ilaria14, Johannes Nippgen15. 1. Department of Urologie, Universitätsmedizin Rostock, Rostock, Germany. Electronic address: oliver.hakenberg@med.uni-rostock.de. 2. Clinica Universidad De Navarra, Pamplona, Spain. Electronic address: jlgracia@unav.es. 3. Medical Oncology Department (CiberOnc), Hospital 12 De Octubre, Madrid, Spain. Electronic address: cdanicas@hotmail.com. 4. Centrum Onkologii - Instytut im. Marii Sklodowskiej-Curie, Warsaw, Poland. Electronic address: demkow@coi.waw.pl. 5. Department of Urology, Josa Andras Teaching Hospital, Nyiregyhaza, Hungary. Electronic address: tarekali@freemail.hu. 6. Medical Oncology Department, Santa Chiara Hospital, Trento, Italy. Electronic address: orazio.caffo@apss.tn.it. 7. Department of Urology and Uro-Oncology, University Hospital Cologne, Cologne, Germany. Electronic address: axel.heidenreich@uk-koeln.de. 8. Department of Urology, University of Freiburg, Freiburg, Germany. Electronic address: wolfgang.schultze-seemann@uniklinik-freiburg.de. 9. CHU Sart Tilman, University of Liège, Liège, Belgium. Electronic address: brieuc.sautois@chu.ulg.ac.be. 10. Department of Urology, General University Hospital, And First Faculty of Medicine, Charles University, Prague, Czech Republic. Electronic address: ivan.pavlik@vfn.cz. 11. Eli Lilly and Company, Bridgewater, NJ, USA. Electronic address: aqin@dsi.com. 12. Eli Lilly and Company, NY, USA. Electronic address: ruslan.novosiadly@lilly.com. 13. Eli Lilly and Company, Basingstoke, United Kingdom. Electronic address: shahir_ashwin@lilly.com. 14. Eli Lilly and Company, Indianapolis, IN, USA. Electronic address: cancerdoc@mac.com. 15. Eli Lilly and Company, Bridgewater, NJ, USA. Electronic address: dr.nippgen@web.de.
Abstract
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 afterdocetaxel. 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 toM/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.
RCT Entities:
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.
Authors: Brian A Van Tine; Rangaswamy Govindarajan; Steven Attia; Neeta Somaiah; Scott S Barker; Ashwin Shahir; Emily Barrett; Pablo Lee; Volker Wacheck; Samuel C Ramage; William D Tap Journal: J Oncol Pract Date: 2019-07-03 Impact factor: 3.840