765PD - Safety of radium-223 dichloride (Ra) with docetaxel (D) in patients (pts) with bone metastases (mets) from castration-resistant prostate cancer (CR...

Date 28 September 2014
Event ESMO 2014
Session Genitourinary tumours, prostate
Topics Anti-Cancer Agents & Biologic Therapy
Supportive Care
Prostate Cancer
Presenter Michael Morris
Citation Annals of Oncology (2014) 25 (suppl_4): iv255-iv279. 10.1093/annonc/mdu336
Authors 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
  • 1Oncology, Memorial Sloan-Kettering Cancer Center, 10128 - New York/US
  • 2Medical Oncology, University of Washington, 98109 - Seattle/US
  • 3Medicine, Memorial Sloan-Kettering Cancer Center, 10128 - New York/US
  • 4Lank Center For Genitourinary Oncology, Dana Farber Cancer Institute, 02115 - Boston/US
  • 5Oncology, Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, 21287 - Baltimore/US
  • 6Medical Oncology, NorthShore University HealthSystem, Evanston/US
  • 7Oncology, UCSF Helen Diller Family Comprehensive Cancer Center, 94115 - San Francisco/US
  • 8Department Of Cancer Medicine, Institut Gustave Roussey, 94805 - Villejuif/FR
  • 9Department Of Cancer Medicine, Institut Gustave Roussy, 94805 - Villejuif/FR
  • 10Molecular Imaging And Therapy Service, Memorial Sloan-Kettering Cancer Center, 10128 - New York/US
  • 11Oncology Global Clinical Programs, Bayer HealthCare, Whippany/US
  • 12Clinical Department, Algeta ASA (Bayer), Oslo/NO
  • 13Clinical Research, Algeta ASA (Bayer), Oslo/NO

Abstract

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.

Patient Data and Characteristics From Expanded Safety Cohort Ra + Docetaxel n = 33 Docetaxel n = 13
No. of patients in treatment 10 4
No. of patients who discontinued study treatment 6 5
No. of patients in follow-up 13 4
No. of patients who completed study 4 0
Age, median (min-max), y 68 (49-82) 67 (55-82)
Weight, median (min-max), kg 87 (58-119) 77 (67-131)
PSA, median (min-max), &mgr;g/L 99 (3-1000) 43 (4-1042)
Total ALP, median (min-max), &mgr;g/L 167 (62-1016) 284 (74-472)
Bone ALP, median (min-max), &mgr;g/L 36 (10-331) 43(16-164)
LDH, median (min-max), U/L 191 (123-418) 195 (124-328)
Mean (min-max) nadir platelet count, thou/cumm, on treatment 261.9 (162-332) 231 (139-314)
Mean (min-max) nadir absolute neutrophil count, thou/&mgr;L, on treatment 1.4 (0.2-5.5) 0.6 (0.1-1.2)
Extent of disease 2-4 metastases5-9 metastases10-20 metastases> 20 metastases 36911 0346

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 Bayer

C.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.