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Poster display

2723 - Radium-223 with concomitant bone-targeting agents in metastatic castration-resistant prostate cancer (CRPC) patients treated in an international early access program (EAP)

Date

09 Oct 2016

Session

Poster display

Presenters

Fred Saad

Citation

Annals of Oncology (2016) 27 (6): 243-265. 10.1093/annonc/mdw372

Authors

F. Saad1, A. Heidenreich2, D. Heinrich3, D. Keizman4, J.M. O'Sullivan5, J. Carles6, M. Wirth7, K. Miller8, J. Gratt9, M. Seger-van Tol10, S. Nilsson11, S. Gillessen12

Author affiliations

  • 1 Department Of Surgery, University of Montreal Hospital Center, QC H2X 0A9 - Montreal/CA
  • 2 Department Of Urology, University Hospital Cologne, Köln/DE
  • 3 Department Of Oncology, Akershus University Hospital, Lorenskog/NO
  • 4 Genitourinary Oncology Service, Meir Medical Center, Kfar Saba/IL
  • 5 The Centre For Cancer Research And Cell Biology, Queen’s University Belfast, and the Northern Ireland Cancer Centre, Belfast/GB
  • 6 Department Of Oncology, Vall d`Hebron University Hospital Institut d'Oncologia, 08035 - Barcelona/ES
  • 7 Department Of Urology, University Hospital Carl-Gustav Carus, Dresden/DE
  • 8 Department Of Urology, Charité University Medicine Berlin, 10117 - Berlin/DE
  • 9 Biostatistics, Modular Informatics LLC, New York/US
  • 10 Pharmaceutical Division, Bayer, Whippany/US
  • 11 Department Of Oncology-pathology, Karolinska University Hospital, Stockholm/SE
  • 12 Department Of Oncology/haematology, Kantonsspital St. Gallen, 9007 - St. Gallen/CH
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Resources

Abstract 2723

Background

The bone-targeting agents (BTAs) denosumab and bisphosphonates (BPs) are widely used in the supportive care of patients (pts) with CRPC and bone metastases. We present data on pts treated with radium-223 dichloride (Ra-223) with or without a concomitant BTA in an international EAP.

Methods

This was a prospective single-arm phase IIIb study of CRPC pts with symptomatic or asymptomatic bone metastases (no visceral disease) recruited from 14 countries. Pts received Ra-223 50 kBq/kg [55 kBq/kg after NIST update] (iv injection) every 4 weeks for 6 cycles. Co-primary endpoints were safety and overall survival (OS). Exploratory analyses investigated the effects of concomitant denosumab (no BPs) or BPs (no denosumab) on OS and symptomatic skeletal events (SSE).

Results

696 pts received at least one Ra-223 cycle. Of those, 127 (18%) pts were treated with concomitant denosumab (no BPs) and 435 (63%) without concomitant BTAs. Key baseline characteristics are reported in pts treated with Ra-223 with or without a concomitant BTA (Table). Median OS (mOS) and median time to first SSE (mSSE) were longer in pts treated with Ra-223 and denosumab versus pts without a concomitant BTA (Table). While key baseline characteristics in pts treated with Ra-223 and denosumab were similar to pts treated with Ra-223 and BPs (no denosumab, 125 [18%] of 696), adding BPs to Ra-223 did not appear to improve mOS. However, mSSE was prolonged in pts receiving Ra-223 and BPs versus pts who received Ra-223 without a concomitant BTA (Table).

Concomitant treatment with Ra-223 (administered after the first injection of Ra-223, or before the study and continued after the first Ra-223 injection)

Denosumab BPs No denosumab /no BPs
N = 127 N = 125 N = 435
Baseline characteristics
ECOG PS, n (%)
0 58 (46%) 55 (44%) 144 (33%)
1 55 (43%) 54 (43%) 234 (54%)
≥2 14 (11%) 16 (13%) 57 (13%)
Pain, n (%) 123 122 413
Mild 75 (61%) 72 (59%) 218 (53%)
Moderate-severe 19 (15%) 24 (20%) 113 (27%)
None 29 (24%) 26 (21%) 82 (20%)
ALP (U/L), n 127 125 433
Median 121.0 137.0 168.0
PSA (µg/L), n 127 124 433
Median 91.2 118.5 174.6
Efficacy outcome
Overall survival
Median, months NR 12.7 13.4
95% CI NA 10.9–NA 11.7–NA
Hazard ratio (95% CI) 0.630 (0.431–0.922) 0.846 (0.584–1.226) -
Time to first SSE
Median, months 17.0 NR 15.8
95% CI 17.0–17.5 NA 10.9–19.1
Hazard ratio (95% CI) 0.761 (0.493–1.173) 0.498 (0.294–0.845) -

NR/A = not reached/available.

Conclusions

In this EAP, pts treated with Ra-223 and a concomitant BTA appeared to have longer time to first SSE than those treated without a concomitant BTA. However, improvement in OS with a BTA was observed with denosumab but not with BPs. Prospective randomized controlled studies are required to confirm the benefit of this specific treatment combination in metastatic CRPC.

Clinical trial identification

ClinicalTrials.gov NCT01618370

Legal entity responsible for the study

Pharmaceutical Division of Bayer

Funding

Pharmaceutical Division of Bayer

Disclosure

F. Saad: Grants, personal fees and non-financial support from Bayer, Amgen, Janssen, and Astellas, during the conduct of the study.

A. Heidenreich: Grants and personal fees from Bayer during the conduct of the study; grants and personal fees from Astellas and Sanofi Aventis, personal fees from Amgen, Dendreon, Ferring, Hexal, IPSEN, Janssen-Cilag, Pfizer, and Takeda; outside the submitted work.

D. Heinrich: Grant from Bayer, during the conduct of the study; personal fees from Bayer, Amgen, Astellas, Sanofi, and Johnson & Johnson, outside the submitted work.

J.M. O'Sullivan: Advisory boards for: Bayer, Astellas, Sanofi.

J. Carles: Scientific advisory board membership/consultancy: Johnson & Johnson, Astellas, Bayer, Amgen, Pfizer, BMS; Speakers Bureau: Bayer, Johnson & Johnson.

M. Wirth: Personal fees from Apogepha, Astellas, Bayer, Janssen-Cilag, Merck, Roche, and Sanofi-Aventis outside the submitted work.

K. Miller: Advisory board membership: Bayer.

J. Gratt: Personal fees from Bayer Healthcare during the conduct of the study.

M. Seger-van Tol: Employment: Bayer.

S. Nilsson: Participated in Bayer Healthcare advisory boards and as speaker in scientific meetings.

S. Gillessen: Advisory Boards (compensated): Astellas, Bayer, Curevac, Dendreon, Janssen Cilag, Janssen Diagnostics, Millennium, Novartis, Orion Pharma, Pfizer, Sanofi Aventis. Speakers Bureau (without honorarium): Bayer. Pending patent application: WO 2009138392 A1.

All other authors have declared no conflicts of interest.

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