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.
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).
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 Cmax was 0.263 kBq/mL (33%). Most common tx-related AEs (>5%) were nausea, anemia, diarrhea, vomiting, decreased appetite, and decreased platelets. Table:
|Mean % change, baseline to 12 wk||LOCF* N = 70||OCâ N = 33||LOCF* N = 70||OCâ N = 33|
|Mean (SD)||−23.9 (30.1)||−28.4 (28.3)||85.68 (143.28)||91.42 (135.55)|
|Response (changes ≤12 wkâ¡), 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)|
|NormalizationÂ§, N = 40|
|n (%)||8 (20.0)||8 (20.0)||Not applicable||Not applicable|
*Last observation carried forward; pts with nonmissing baseline values
â Observed 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.
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
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.