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 Anticancer agents
Supportive Measures
Prostate Cancer
Therapy
Biological Therapy
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.