Abstract 803
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 à 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 | 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) |
| Normalization§, 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
§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.