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

Date

19 Dec 2015

Session

Genitourinary tumours

Presenters

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

Author affiliations

  • 1 Department Of Urology, Shanghai Changhai Hospital, 200433 - Shanghai/CN
  • 2 Department Of Nuclear Medicine, Zhongshan Hospital, Fudan University, Shanghai/CN
  • 3 Department Of Urology, National Taiwan University Hospital, Taipei/TW
  • 4 Department Of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul/KR
  • 5 Department Of Urology, Chonnam National University Hospital, Gwangju/KR
  • 6 Department Of Medical Oncology, Sungkyunkwan University, Samsung Medical Center, Seoul/KR
  • 7 Division Of Urology, Department Of Surgery, Kaohsiung Veterans General Hospital, Kaohsiung/TW
  • 8 Department Of Medical Oncology, National Cancer Centre, Singapore/SG
  • 9 Department Of Oncology, Seoul National University Hospital, Seoul/KR
  • 10 Department Of Hematology Oncology, National University Hospital, Singapore/SG
  • 11 Department Of Medical Oncology, OncoCare Cancer Centre, - - Singapore/SG
  • 12 Department Of Urology, Huashan Hospital, Fudan University, Shanghai/CN
  • 13 Department Of Nuclear Medicine, Peking Union Medical College Hospital, Beijing/CN
  • 14 Department Of Nuclear Medicine And Pet, Singapore General Hospital, Singapore/SG
  • 15 Department Of Global Development - Portfolio & Operations, Bayer HealthCare Company Ltd., Beijing/CN
  • 16 Department Of Gds&a, Bayer HealthCare Company Ltd., Beijing/CN
  • 17 Department Of Urology, Zhongshan Hospital, Fudan University, Shanghai/CN
More

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.

Resources from the same session

This site uses cookies. Some of these cookies are essential, while others help us improve your experience by providing insights into how the site is being used.

For more detailed information on the cookies we use, please check our Privacy Policy.

Customise settings