Background: When the ALSYMPCA study that reported improved overall survival (OS) in bone symptomatic mCRPC patients (pts) treated with radium-223 (Ra-223) vs placebo (median 14.9 vs 11.3 months [mos], HR = 0.70) was conducted, few treatment alternatives with OS benefit were available. Due to its unique mode of action, interference of Ra-223 with novel endocrine agents is not expected. Here we present data on Ra-223 with concomitant abiraterone (Abi) and/or enzalutamide (Enza) from EAP pts recruited in 14 countries (Europe, Canada and Israel).
Methods: The EAP was a prospective phase IIIb study of mCRPC pts with symptomatic or asymptomatic bone metastases (no visceral disease). Pts received Ra-223 50 kBq/kg (iv injection) every 4 weeks for 6 cycles. Concomitant treatment was defined as any agent given after the first Ra-223 injection or prior to Ra-223 initiation and continued during Ra-223 treatment. Effects of concomitant Abi or Enza on OS and safety were investigated.
Results: Of 696 pts treated with Ra-223, 154 (22%) received concomitant Abi, 50 (7%) Enza and 15 both Abi and Enza; a total of 189 pts (27%) received Abi and/or Enza (Abi/Enza). 277 (40%) and 56 (8%) pts had received Abi or Enza prior to Ra-223, respectively. 75% of pts receiving concomitant Abi/Enza and 54% receiving Ra-223 alone had received prior docetaxel. From the first Ra-223 injection, median time on concomitant Abi or Enza was 24.9 and 15.5 weeks, respectively.
Baseline characteristics were largely comparable, median PSA (164.2 vs 98.9 μg/L) and ALP (161.0 vs 142.0 U/L) levels were higher in pts receiving Ra-223 alone vs Ra-223 with concomitant Abi/Enza. OS and safety are summarized (Table).
Median OS was not reached in the concomitant groups vs 13 mos in the Ra-223 alone group. In the concomitant treatment groups AE rates were comparable with the Ra-223 alone group. Grade ⩾3 hematological AEs in the concomitant Abi/Enza vs Ra-223 alone group included anemia, (12% each), thrombocytopenia (1% vs 3%), leukopenia (1% vs <1%), and neutropenia (1% each). Grade 3/4 diarrhea was reported in <1% of pts in the concomitant Abi/Enza and Ra-223 alone groups.
| Median, mos | Abi* (N = 154) | Enza* (N = 50) | Abi/Enza* (N = 189) | Ra-223 alone (N = 507) |
| Abi* (N = 154) | Enza* (N = 50) | Abi/Enza* (N = 189) | Ra-223 alone (N = 507) | |
| OS | ||||
| Median, mos | NR | NR | NR | 13 |
| 95% CI | 16–NE | 12–NE | 16–NE | 12–16 |
| TEAEs | ||||
| Any | 124 (81%) | 38 (76%) | 152 (80%) | 394 (78%) |
| Grade 3/4 | 61 (40%) | 17 (34%) | 75 (40%) | 195 (38%) |
| Grade 5 | 4 (3%) | 3 (6%) | 7 (4%) | 50 (10%) |