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

Resources

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Abstract 243PD

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 Ã 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 Â± 6.4% at 15 min to 0.4 Â± 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 C_max 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^â N = 33	LOCF* N = 70	OC^â N = 33
Mean (SD)	−23.9 (30.1)	−28.4 (28.3)	85.68 (143.28)	91.42 (135.55)
Response (changes ≤12 wk^â¡), 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^Â§, N = 40
n (%)	8 (20.0)	8 (20.0)	Not applicable	Not applicable

*Last observation carried forward; pts with nonmissing baseline values

^âObserved case; pts with nonmissing values, baseline & wk 12

^â¡Max tALP decrease after tx; decrease confirmed ∼ ≥ 4 wk later

^Â§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.