768P - External-beam radiation therapy (EBRT) use and safety with radium-223 dichloride (Ra) in patients (pts) with castration-resistant prostate cancer (...

Date 27 September 2014
Event ESMO 2014
Session Poster Display session
Topics Anti-Cancer Agents & Biologic Therapy
Supportive Care
Prostate Cancer
Surgery and/or Radiotherapy of Cancer
Presenter Joe O'Sullivan
Citation Annals of Oncology (2014) 25 (suppl_4): iv255-iv279. 10.1093/annonc/mdu336
Authors J.M. O'Sullivan1, O. Sartor2, C. Parker3, P. Hoskin4, A. Widmark5, B. Mellado6, S.I. Helle7, A. Aksnes8, J.E. Garcia-Vargas9, S. Nilsson10
  • 1Cancer Research And Cell Biology, Centre for Cancer Research and Cell Biology, Queen's University, BT9 7AB - Belfast/GB
  • 2Department Of Medicine: Section Of Hematology & Medical Oncology And Department Of Urology, Tulane Cancer Center, 70112 - New Orleans/US
  • 3Academic Urology, The Royal Marsden NHS Foundation Trust and Institute of Cancer Research, Sutton/GB
  • 4Oncology, Mount Vernon Hospital Cancer Centre, Middlesex/GB
  • 5Radiation Sciences, Oncology, Umeå University, Umeå/SE
  • 6Medical Oncology, Hospital Clinic, 08036 - Barcelona/ES
  • 7Oncology, Haukeland University Hospital, Bergen/NO
  • 8Clinical Research, Algeta ASA, Oslo/NO
  • 9Oncology Global Clinical Programs, Bayer HealthCare, Whippany/US
  • 10Clinical Oncology, Karolinska University Hosiptal, 171 76 - Stockholm/SE

Abstract

Aim

Bone mets in CRPC frequently cause symptomatic skeletal events (SSEs) requiring EBRT for pain. In ALSYMPCA, Ra, a first-in-class α-emitter, improved overall survival and delayed time to first SSE (Parker NEJM 2013). This post hoc study analyzed ALSYMPCA pts with EBRT for bone pain before randomization and during treatment (tx).

Methods

Eligible pts had symptomatic CRPC with ≥ 2 bone mets and no known visceral mets; had best standard of care; and had prior docetaxel (pD) or were unfit for, lacked access to, or declined docetaxel (no pD). Pts were stratified by prior docetaxel use (yes/no), baseline total alkaline phosphatase level (ALP; < 220 U/L or ≥ 220 U/L), and current bisphosphonate use (yes/no), and randomized 2:1 to 6 injections of Ra (50 kBq/kg IV q 4 wk) or placebo (pbo). EBRT use for bone pain was assessed. Adverse events were analyzed by concomitant EBRT.

Results

Of 921 ALSYMPCA pts, 30% (186/614) Ra pts and 34% (105/307) pbo pts had EBRT for bone pain. Time to EBRT was significantly longer with Ra vs pbo (HR = 0.67, P = 0.001). Ra vs pbo delayed time to EBRT in pts with < 20 mets (HR = 0.49, P < 0.001), current bisphosphonate use (HR = 0.47, P = 0.004), total ALP < 220 (HR = 0.66, P = 0.008), and no pD (HR = 0.65, P = 0.038). In pts with prior EBRT, a higher percentage of pbo vs Ra pts (33% vs 24%) had EBRT for bone pain during the 6 mo of tx. In pts with no prior EBRT, this percentage was also higher for placebo (33% vs 20%), and the difference was even greater at 12 mo after randomization (41% vs 29%). Ra safety profiles were similar with and without concomitant EBRT (Table).

Without Concomitant EBRT With Concomitant EBRT
Patients with AEs, n(%) Radium-223 n = 373 Placebo n = 161 Radium-223 n = 227 Placebo n = 140
Hematologic
Anemia 110 (30) 41 (26) 77 (34) 51 (36)
Neutropenia 16 (4) 2 (1) 14 (6) 1 (1)
Thrombcytopenia 42 (11) 9 (6) 27 (12) 8 (6)
Nonhematologic
Diarrhea 80 (21) 19 (12) 71 (31) 26 (19)
Nausea 115 (31) 43 (27) 98 (43) 61 (44)
Vomiting 55 (15) 15 (9) 56 (25) 26 (19)
Constipation 54 (15) 29 (18) 54 (24) 35 (25)

Conclusions

Ra delays the need for EBRT for bone pain vs pbo. Prior EBRT does not appear to affect need for EBRT for bone pain in pts receiving Ra. EBRT use does not affect the Ra favorable safety profile.

Disclosure

O. Sartor: has had a consultant or advisory relationship with and has received research funding from Algeta and Bayer; C. Parker: has had a consultant or advisory relationship with Algeta, Bayer, and BNIT. He has also received honoraria from Amgen, Astellas, Bayer, Janssen, Sanofi-Aventis, and Takeda; A. Widmark: is employed part-time as an advisor for Sanofi Oncology; A. Aksnes: is employed by Algeta ASA.

J.E. Garcia-Vargas: is employed by Bayer HealthCare; S. Nilsson: has had a consultant or advisory relationship with Algeta and has received remuneration from Bayer HealthCare for travel costs and accommodation for study and writing meetings. All other authors have declared no conflicts of interest.