Introduction

Radium-223 (Ra-223), a targeted alpha therapy, significantly improved overall survival (OS) versus (vs) placebo (pbo) for patients (pts) with metastatic castration resistant prostate cancer (mCRPC) in ALSYMPCA trial (HR = 0.70; 95% CI, 0.58-0.83; P < 0.001) and was well tolerated. We hypothesized that outcome with Ra-223 in ALSYMPCA is similar whether or not pts underwent radical local therapy (RLT) for prostate cancer (PC) at initial diagnosis.

Methods

ALSYMPCA eligible pts had progressive mCRPC with ≥2 bone lesions and no known visceral metastases. Pts were randomized 2:1 to 6 injections of Ra-223 (55 kBq/kg IV; q4 wk) plus best standard of care (BSoC) or matching pbo plus BSoC. Exploratory subgroup analyses were performed to evaluate outcome of Ra-223 vs pbo by RLT (defined as radical prostatectomy or radiation to prostate) and according to metastatic status at initial diagnosis.

Results

921 pts were treated (Ra-223, n = 614; pbo, n = 307). 392 (43%) received RLT at initial diagnosis and 529 (57%) did not. Median OS was longer with Ra-223 vs pbo regardless of whether pts received RLT or not [(with RLT: 15.3 vs 11.8 mo, HR: 0.704 (0.523-0.948); without RLT: 14.7 vs 10.8 mo; HR: 0.684 (0.543-0.862)] (table). _x000D_ _x000D_ Metastatic status at diagnosis was documented for 576 pts (63%); 306 were documented as non-metastatic (M0) and 270 as metastatic (M1). Median OS was longer with Ra-223 vs pbo regardless of metastatic status at diagnosis [M0: 14.1 vs 9.6 mo, HR: 0.674 (0.491-0.925); M1: 15.6 vs 11.5 mo, HR: 0.638 (0.454-0.895)] (table)._x000D_ _x000D_ Therapies received prior to ALSYMPCA trial initiation were mainly RLT (mostly M0), bilateral orchiectomy, LHRH agonist, anti-androgens, chemotherapy and external radiotherapy to bone. These prior therapies were generally balanced between Ra-223 and pbo groups. _x000D_ _x000D_ Safety and pts demographics for the subgroups will be presented. _x000D_ _x000D_ _x000D_

Conclusions

Compared with pbo, Ra-223 improved OS in mCRPC patients. A subgroup analysis indicates that OS is consistent regardless of whether pts had received RLT or not at initial diagnosis. Similarly, OS is consistent regardless of metastatic status at initial diagnosis.

Funding

Bayer Pharmaceuticals