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:
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:
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):
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
Presented by: Celestia Higano, MD, University of Washington, Seattle Washington
Written by: Zachary Klaassen, MD, MSc – Assistant Professor of Urology, Georgia Cancer Center, Augusta University/Medical College of Georgia Twitter: @zklaassen_md at the 2020 Genitourinary Cancers Symposium, ASCO GU #GU20, February 13-15, 2020, San Francisco, California
References:
1. Parker C, Nilsson S, Heinrich D, et al. Alpha emitter radium-223 and survival in metastatic prostate cancer. N Engl J Med 2013;369(3):213-223.
2. Parker CC, Coleman RE, Sartor O, et al. Three-year Safety of Radium-223 Dichloride in Patients with Castration-resistant Prostate Cancer and Symptomatic Bone Metastases from Phase 3 Randomized Alpharadin in Symptomatic Prostate Cancer Trial. Eur Urol 2018 Mar;73(3):427-435.
Written by: Zachary Klaassen, MD, MSc – Assistant Professor of Urology, Georgia Cancer Center, Augusta University/Medical College of Georgia Twitter: @zklaassen_md at the 2020 Genitourinary Cancers Symposium, ASCO GU #GU20, February 13-15, 2020, San Francisco, California
References:
1. Parker C, Nilsson S, Heinrich D, et al. Alpha emitter radium-223 and survival in metastatic prostate cancer. N Engl J Med 2013;369(3):213-223.
2. Parker CC, Coleman RE, Sartor O, et al. Three-year Safety of Radium-223 Dichloride in Patients with Castration-resistant Prostate Cancer and Symptomatic Bone Metastases from Phase 3 Randomized Alpharadin in Symptomatic Prostate Cancer Trial. Eur Urol 2018 Mar;73(3):427-435.