243PD - Phase 3 study of radium-223 dichloride (Ra-223) in Asian patients (pts) with castration-resistant prostate cancer (CRPC) and symptomatic bone metas...

Date 19 December 2015
Event ESMO Asia 2015 Congress
Session Genitourinary tumours
Topics Supportive Care
Prostate Cancer
Presenter Yinghao Sun
Citation Annals of Oncology (2015) 26 (suppl_9): 71-79. 10.1093/annonc/mdv524
Authors Y. Sun1, H. Shi2, C. Chen3, J.L. Lee4, T.W. Kang5, S.H. Park6, T. Wu7, Q.S. Ng8, B. Keam9, S.C.A. Wong10, M.H. Tay11, Q. Ding12, F. Li13, D.C.E. Ng14, X. Liu15, Z. Zhang16, J. Guo17
  • 1Department Of Urology, Shanghai Changhai Hospital, 200433 - Shanghai/CN
  • 2Department Of Nuclear Medicine, Zhongshan Hospital, Fudan University, Shanghai/CN
  • 3Department Of Urology, National Taiwan University Hospital, Taipei/TW
  • 4Department Of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul/KR
  • 5Department Of Urology, Chonnam National University Hospital, Gwangju/KR
  • 6Department Of Medical Oncology, Sungkyunkwan University, Samsung Medical Center, Seoul/KR
  • 7Division Of Urology, Department Of Surgery, Kaohsiung Veterans General Hospital, Kaohsiung/TW
  • 8Department Of Medical Oncology, National Cancer Centre, Singapore/SG
  • 9Department Of Oncology, Seoul National University Hospital, Seoul/KR
  • 10Department Of Hematology Oncology, National University Hospital, Singapore/SG
  • 11Department Of Medical Oncology, OncoCare Cancer Centre, - - Singapore/SG
  • 12Department Of Urology, Huashan Hospital, Fudan University, Shanghai/CN
  • 13Department Of Nuclear Medicine, Peking Union Medical College Hospital, Beijing/CN
  • 14Department Of Nuclear Medicine And Pet, Singapore General Hospital, Singapore/SG
  • 15Department Of Global Development - Portfolio & Operations, Bayer HealthCare Company Ltd., Beijing/CN
  • 16Department Of Gds&a, Bayer HealthCare Company Ltd., Beijing/CN
  • 17Department Of Urology, Zhongshan Hospital, Fudan University, Shanghai/CN

Abstract

Aim/Background

Ra-223 is approved for pts with CRPC, symptomatic bone mets, and no visceral mets. This study evaluated efficacy and safety of Ra-223 + best standard of care (BSoC) in Asian pts with CRPC and symptomatic bone mets.

Methods

These are interim results of Ra-223 effect on total alkaline phosphatase (tALP) and prostate-specific antigen (PSA) dynamics, pharmacokinetics (PK) in a Chinese pt subset, and safety. Pts had progressive, symptomatic CRPC, ≥2 bone mets, no visceral mets, and were docetaxel ineligible. Pts were to have 6 injections (inj) Ra-223 (50 kBq/kg IV) q4wk × 6 + BSoC. Blood samples for clinical chemistry were assessed ≤2 d pre-inj. Primary efficacy was tALP % change from baseline at 12 wk. tALP and PSA response and normalization were also reported. PK blood samples came from a Chinese pt subset up to 72 h after first dose. Safety included adverse events (AEs).

Results

At data cutoff, 115 pts were enrolled; 70 had ≥1 inj; 15 discontinued treatment (tx) early. 9 pts (valid PK data) were in the PK analysis. Table shows mean % changes in tALP and PSA from baseline at 12 wk, and tALP and PSA response and normalization. 24% and 3% pts had ≥50% decreases in tALP and PSA, respectively. Radioactivity cleared rapidly after 1 Ra-223 dose; fraction of remaining activity decreased: 14.5 ± 6.4% at 15 min to 0.4 ± 0.4% at 72 h. Geometric mean (coefficient of variation, %) of Ra-223 AUC(0-last) was 0.456 kBq*h/mL (82%); Ra-223 Cmax was 0.263 kBq/mL (33%). Most common tx-related AEs (>5%) were nausea, anemia, diarrhea, vomiting, decreased appetite, and decreased platelets. Table:

tALP tALP PSA PSA
Mean % change, baseline to 12 wk LOCF* N = 70 OC† N = 33 LOCF* N = 70 OC† N = 33
Mean (SD) −23.9 (30.1) −28.4 (28.3) 85.68 (143.28) 91.42 (135.55)
Response (changes ≤12 wk‡), N = 70
Decrease vs baseline, n (%)
≥30% 35 (50.0) 35 (50.0) 5 (7.1) 5 (7.1)
≥50% 17 (24.3) 17 (24.3) 2 (2.9) 2 (2.9)
Confirmed decrease vs baseline, n (%)
≥30% 22 (31.4) 22 (31.4) 2 (2.9) 2 (2.9)
≥50% 8 (114.3) 8 (114.3) 1 (1.4) 1 (1.4)
Normalization§, N = 40
n (%) 8 (20.0) 8 (20.0) Not applicable Not applicable

*Last observation carried forward; pts with nonmissing baseline values

†Observed case; pts with nonmissing values, baseline & wk 12

‡Max tALP decrease after tx; decrease confirmed ∼ ≥ 4 wk later

§Normal range at 12 wk (2 consecutive measurements, ≥2 wk apart) after tx start if baseline value > upper limits of normal.

Conclusions

Ra-223 decreased serum markers of CRPC activity. Radioactivity cleared rapidly from blood. Ra-223 PK data in 9 Chinese pts were in line with early phase 1 results. Ra-223 was safe and well tolerated.

Clinical trial identification

NCT01810770

Disclosure

T.L. Wu: ownership interest in Pfizer. Q.S. Ng: served on the Advisory Board for Bayer. M.H. Tay: honoraria from Bayer for attending an advisory board meeting. D.C.E. Ng: research funding from Bayer, as principal investigator of Bayer-sponsored trials. X. Liu, Z. Zhang: employed by Bayer HealthCare Company Ltd. All other authors have declared no conflicts of interest.