(UroToday.com) Dr. Daniel Song presents the results of the non-interventional REASSURE study, which examined the Real-world safety and effectiveness of radium-223 (223Ra) in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC) treated in the US.
Radium-223 (223Ra) is an established treatment for patients for men with castration resistant prostate cancer and symptomatic bony metastatic disease, based on its proven improved overall survival (OS), improved quality of life, and demonstrated favorable safety in the phase 3 ALSYMPCA trial.1 Its use remains relatively minimal in most clinical practices, however, especially in the face of the multiple new agents for men with advanced prostate cancer.
REASSURE (NCT02141438) is a global, prospective, single-arm, observational study of 223Ra use in pts with mCRPC and bone metastases in routine clinical practice. It was meant to assess short and long term safety data with 7 years follow-up. Herein, the authors present clinical outcomes from the second planned interim analysis of REASSURE for pts treated in the US. The authors note and acknowledge that practice patterns, drug availability, and treatment landscape differ in the US than in other parts of the world.
The study design is below:
This analysis included pts with confirmed mCRPC with bone metastases scheduled to receive 223Ra in the US. All pts received ≥1 dose of 223Ra. Primary endpoints are short- and long-term safety, including incidence of bone marrow suppression and second primary malignancies (SPM). Secondary endpoints included OS and pt-reported pain (Brief Pain Inventory – Short Form [BPI–SF] scores). A clinically meaningful pain response was defined as a decrease from baseline of ≥2 points in BPI-SF worst pain item.
Between 2014–2017, a total of 498 pts were included in this analysis. At the data cut-off (20 March 2019), the median duration of observation was 11.9 months (0.4–41.3). Most pts (81%) had bone metastases only; 69% of pts received 5–6 223Ra injections.
Demographics are summarized below:
In addition to Radium-223, patients received a multitude of additional agents. Overall, 77% of pts had received ≥1 prior life-prolonging therapy: abiraterone (45%), enzalutamide (48%), docetaxel (25%), cabazitaxel (6%), or sipuleucel-T (24%). Concomitant enzalutamide was received by 31% of pts, and 47% received concomitant bone health agents. After 223Ra, 31% of pts received ≥1 life prolonging therapies.
During treatment, 208/358 (58%) pts with a baseline BPI-SF ≥2 had a clinically meaningful pain response.
As for safety, any-grade and grade ≥3 drug-related treatment-emergent adverse events (TEAEs) occurred in 32% and 10% of pts, respectively. Drug-related TEAEs resulted in 223Ra discontinuation in 4% of pts. Treatment-emergent and drug-related serious AEs (SAEs) occurred in 21% and 6% of pts, respectively. The most common (>5% of pts) any-grade drug-related TEAEs were diarrhea (10%), fatigue (9%), anemia (8%), and nausea (7%). Overall, 4% of pts had fractures; 2% of pts developed bone disorders. Eleven SPMs occurred in 10 pts (2%). In total, 60% of pts died during study follow-up.
The take-home point here is that there were no new signals of adverse events or concerning findings.
Median OS was 17.8 months (95% CI 15.6–19.4).
Despite its limited use and uptake, this study demonstrates continued efficacy in the real world - median OS after 223Ra treatment was close to 18 months. A majority of patients completed 5–6 223Ra injections. The known safety profile of 223Ra was confirmed with no new safety signals. Over half of patients with pain at baseline had a clinically meaningful pain response during 223Ra treatment.
However, it should be noted that these patients were enrolled in 2014-2017, and the treatment landscape has drastically changed since then. I doubt as much Radium-223 is being used as much now.
Presented by: Daniel Song, MD, Johns Hopkins Medicine, Baltimore, MDWritten by: Thenappan (Thenu) Chandrasekar, MD – Urologic Oncologist, Associate Professor of Urology, University of California, Davis, @tchandra_uromd @UCDavisUrology on Twitter during the 2023 American Society of Clinical Oncology (ASCO) Annual Meeting, Chicago, IL, Fri, June 2 – Tues, June 6, 2023.
References:
- Hoskin P, Sartor O, O'Sullivan JM, Johannessen DC, Helle SI, Logue J, Bottomley D, Nilsson S, Vogelzang NJ, Fang F, Wahba M, Aksnes AK, Parker C. Efficacy and safety of radium-223 dichloride in patients with castration-resistant prostate cancer and symptomatic bone metastases, with or without previous docetaxel use: a prespecified subgroup analysis from the randomised, double-blind, phase 3 ALSYMPCA trial. Lancet Oncol. 2014 Nov;15(12):1397-406. doi: 10.1016/S1470-2045(14)70474-7. Epub 2014 Oct 17. PMID: 25439694.