Annals of Oncology 25 (Supplement 4): iv255–iv279, 2014 doi:10.1093/annonc/mdu336.13
765PD
SAFETY OF RADIUM-223 DICHLORIDE (RA) WITH DOCETAXEL (D) IN PATIENTS (PTS) WITH BONE METASTASES (METS) FROM CASTRATION-RESISTANT PROSTATE CANCER (CRPC): A PHASE 1/2A CLINICAL TRIAL
M.J. Morris1, C. Higano2, H.I. Scher3, C. Sweeney4, E.S. Antonarakis5, D. Shevrin6, C.J. Ryan7, Y. Loriot8, K. Fizazi9, N. Pandit-Taskar10, J. E. Garcia-Vargas11, K. Lyseng12, M. Bloma12, A. Aksnes13, J.A. Carrasquillo10 1 Oncology, Memorial Sloan-Kettering Cancer Center, New York, NY, USA 2 Medical Oncology, University of Washington, Seattle, WA, USA 3 Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY, USA 4 Lank Center for Genitourinary Oncology, Dana Farber Cancer Institute, Boston, MA, USA 5 Oncology, Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD, USA 6 Medical Oncology, NorthShore University HealthSystem, Evanston, IL, USA 7 Oncology, UCSF Helen Diller Family Comprehensive Cancer Center, San Francisco, CA, USA 8 Department of Cancer Medicine, Institut Gustave Roussey, Villejuif, FRANCE 9 Department of Cancer Medicine, Institut Gustave Roussy, Villejuif, FRANCE 10 Molecular Imaging and Therapy Service, Memorial Sloan-Kettering Cancer Center, New York, NY, USA 11 Oncology Global Clinical Programs, Bayer HealthCare, Whippany, NJ, USA 12 Clinical Department, Algeta ASA (Bayer), Oslo, NORWAY 13 Clinical Research, Algeta ASA (Bayer), Oslo, NORWAY
Aim: Ra is an approved α-emitter that prolongs survival in pts with CRPC and symptomatic bone mets (Parker et al. NEJM. 2013). D is an approved chemotherapy for CRPC. We conducted a phase 1/2a study of Ra + D in CRPC pts with bone mets to establish safety and a recommended dose of the combination. We previously reported dose escalation data and recommended dose (ASCO 2013). Here we report preliminary data on an expansion cohort studying safety of Ra + D vs D alone. Methods: Eligible pts had progressing CRPC with ≥ 2 bone mets and were candidates for D treatment (tx). Pts were randomized 2:1 to the recommended dose (5 × Ra 50 kBq/kg q 6 wk + 10 × D 60 mg/m2 q 3 wk) vs D alone (75 mg/m2 q 3 wk with step-down option to 60 mg/m2). Adverse events were assessed during tx. Long-term safety data were collected q 3 mo for up to 1 year after start of study tx. Accrual is complete. Results: 46 pts are enrolled (dosed) in the expanded safety cohort. Baseline characteristics in the 2 tx arms are presented below (Table); 33 pts had Ra + D, and 13 had D alone. As of May 2014, 13 (Ra + D) vs 4 (D) pts had all planned study tx doses. To date, febrile neutropenia occurred in 2 pts (both had D alone). There were 1 case of grade 3/4 anemia (Ra + D), 2 cases of grade 1 anemia (both D alone), and no thrombocytopenia. Preliminary data for neutrophils and platelets (Table) indicate a nadir ∼ 1 week after injection, with values similar in the 2 tx arms. 3 of 4 pts receiving
D had confirmed dose reductions. A safety review in Nov 2013 raised no concern; recommended Ra + D dose was continued. Table: 765PD Patient Data and Characteristics From Expanded Safety Cohort
Ra + Docetaxel n = 33
Docetaxel n = 13
No. of patients in treatment No. of patients who discontinued study treatment No. of patients in follow-up No. of patients who completed study Age, median (min-max), y Weight, median (min-max), kg PSA, median (min-max), μg/L Total ALP, median (min-max), μg/L Bone ALP, median (min-max), μg/L LDH, median (min-max), U/L Mean (min-max) nadir platelet count, thou/cumm, on treatment Mean (min-max) nadir absolute neutrophil count, thou/μL, on treatment Extent of disease 2-4 metastases 5-9 metastases 10-20 metastases > 20 metastases
10 6
4 5
13 4 68 (49-82) 87 (58-119) 99 (3-1000) 167 (62-1016) 36 (10-331) 191 (123-418) 261.9 (162-332)
4 0 67 (55-82) 77 (67-131) 43 (4-1042) 284 (74-472) 43(16-164) 195 (124-328) 231 (139-314)
1.4 (0.2-5.5)
0.6 (0.1-1.2)
3 6 9 11
0 3 4 6
Conclusions: The expanded safety cohort data confirm that Ra + D was well tolerated at 5 × Ra 50 kBq/kg q 6 wk + 10 × D 60 mg/m2 q 3 wk in pts who had all planned injections. More pts completed Ra + D tx vs D alone. Expanded safety cohort continues as planned. Disclosure: M.J. Morris: has had a consultant or advisory relationship with and has received research funding from Sanofi-Aventis and Algeta; C. Higano: Consultancy in the past 2-years from Bayer and Johnson & Johnson. Research funding from Algeta, Bayer and Janssen; H.I. Scher: D has had a consultancy relationship with Sanofi; D. Shevrin: Consulted with Astellas on Enzalutamide speakers Bureau for Astellas and BayerC.J. Ryan: Consultancy: Bayer Adboard, Millenium Adboard Research funding: Algeta ASA (Bayer) Honoraria directly received from Janssen; Y. Loriot: has served as a consultant for Bayer, has received honoraria from Sanofi and Bayer, and has received research funding from Sanofi; K. Fizazi: has served on the speakers bureau or advisory committee for Sanofi and Bayer; J.E. Garcia-Vargas: is employed by Bayer HealthCare; K. Lyseng: M is employed by Algeta ASA (Bayer); M. Bloma: is employed by and has an ownership interest in Algeta ASA (Bayer); A. Aksnes: D is employed by Algeta ASA (Bayer); J.A. Carrasquillo: has had a consultant or advisory relationship with Bayer and has received honoraria and research funding from Algeta. All other authors have declared no conflicts of interest.
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abstracts
genitourinary tumours, prostate
