ASCO GU 2020: Clinical outcomes and Patient profiles in REASSURE: An Observational Study of Radium-223 (Ra-223) in Metastatic Castration-Resistant Prostate Cancer (mCRPC)

San Francisco, CA ( Radium-223 is a targeted alpha therapy that showed a survival advantage and favorable safety profile in the phase III ALSYMPCA trial in patients with mCRPC.1 Because Radium-223 therapy leads to radiation exposure, it is important to investigate the long-term risk of developing a second primary malignancy. A 3-year safety follow-up of the ALSYMPCA trial (NCT00699751) showed that the cumulative incidence of secondary primary malignancies was low,2 however, there are limited data on the long-term safety of Radium-223 in patients with mCRPC in the real-world setting.  The REASSURE study was designed to assess the short- and long-term safety of Radium-223 in patients with mCRPC in routine clinical practice over a 7-year follow-up. At the prostate cancer session at GU ASCO 2020, Dr. Celestia Higano and colleagues presented results from the second planned interim analysis of REASSURE.

REASSURE is a global, prospective, single-arm, observational study assessing the use of Radium-223 in patients with mCRPC and bone metastasis in routine clinical practice. The second prespecified interim analysis (data cut-off March 20, 2019) evaluated the safety and clinical outcomes of Radium-223 in patients with mCRPC. The primary outcome measures were the incidence of second primary malignancies, bone marrow suppression, and short- and long-term safety in patients who had ≥1 Radium-223 dose. Secondary outcomes included overall survival (OS), the incidence of bone fractures, number of bone-associated events, and patient-reported pain. The full study design is as follows:

ASCO GU 2020 REASSURE follow up timeline
There were 1,465 patients in the safety analysis, with a median follow up of 11.5 months (range: 0-46.9 months). The most common primary reason for ending observation was death (n=933, 64%). The median PSA (n=1053) was 59 ng/mL, median ALP (n=1048) was 135 U/L, and median LDH (n=555) was 269 U/L. Among included patients, 81% had bone metastases only at baseline, 19% of patients had other metastatic sites, mostly in the lymph nodes. There were 19% of patients that had <6 metastatic sites, 47% had 6–20 sites, 20% had >20 lesions but not a superscan, and 6% had a superscan. Among previous therapies utilized 45% had prior abiraterone, 38% prior docetaxel, 37% prior enzalutamide, 9% prior cabazitaxel, and 8% prior sipuleucel-T. The concomitant and subsequent cancer therapies (as well as bone health agents) are as follows:

ASCO GU 2020 REASSURE concomitant and subsequent cancer therapies graph

The median number of Ra-223 doses received was 6, and 67% of patients had ≥5 doses. The secondary primary malignancy rate was only 1%, of which the most common were skin cancer and lung cancer (n=3 each). The most common treatment-emergent drug-related adverse event of any grade was diarrhea (11%). There were 10% of patients that had a bone-associated event, 5% had fractures, and 15% had a hematological adverse event. The median OS was 15.6 months (95% CI 14.6–16.5):

ASCO GU 2020 REASSURE kap meier OS

Of the 39% of patients that received bone health agents, 9% had at least one fracture or bone-associated adverse event. Among 61% of patients that did not have a bone health agent, 11% had at least one fracture or bone-associated adverse event. Mean BPI-SF pain scores were lower during Radium-223 treatment than at baseline, but improvements were not clinically meaningful.

Dr. Higano concluded with several take-home messages from the REASSURE study:

  • In REASSURE, there was a low incidence of secondary primary malignancies, bone fractures, and bone marrow suppression after Radium-223 treatment, with no new adverse events identified
  • Abiraterone/prednisone was the most common prior anticancer therapy
  • This study confirms that in routine clinical practice, Radium-223 adverse event rates were low, and patients generally received ≥5 doses
  • The final data collection is scheduled for December 2023
Clinical trial information: NCT02141438