San Francisco, CA (UroToday.com) The treatment landscape for metastatic castration-resistant prostate cancer (mCRPC) is expanding and now includes chemotherapy, oral hormonal therapies targeting the androgen receptor axis, immunotherapy, and radiopharmaceutical therapy, all of which are known to increase overall survival (OS). While new therapies have been approved for the treatment of mCRPC, validated guidelines for optimal sequencing of approved mCRPC therapies do not exist. Radium-223 was approved by the FDA in 2013 for the treatment of patients with CRPC with bone metastases. At the prostate cancer session at GU ASCO 2020, Dr. Rana McKay and colleagues presented results of their study evaluating treatment patterns and OS among patients with mCRPC treated with Radium-223 in an academic clinical setting.
This study was a retrospective chart review conducted at Dana-Farber Cancer Institute of bone metastases-predominant mCRPC patients treated with Radium-223. Treatment patterns from 2013-2018 were evaluated including Radium-223 initiation pre- versus post-chemotherapy. Demographic and clinical characteristics were captured at the index date. OS was examined using Kaplan-Meier medians and 95% confidence intervals.
There were 220 patients treated with Radium-223, including 64 pre-chemotherapy, 83 post-chemotherapy, and 73 receiving no chemotherapy. The mean age of patients diagnosed with mCRPC was 69.2 years and the mean age at Radium-223 was 71.4 years. Patients were mostly white (88.6%) and approximately half (50.9%) of the patients had Gleason score ≥8 at prostate cancer diagnosis. The median Radium-223 injections per patient were 6.0 and 5.0 in the pre- vs. post-chemotherapy cohorts, respectively (p<0.001). The mean chemotherapy cycles received was 9.0 (pre-chemo) and 9.2 (post-chemo); on average, Radium-223 was given in the 3rd and 5th mCRPC line of therapy (pre- and post-chemo, p<0.001). As follows is a figure of the treatment sequence up to two lines before and after Radium-223:
Furthermore, 41.8% of patients were treated with Radium-223 in combination with another mCRPC therapy, most commonly abiraterone acetate (37.0%) or enzalutamide (44.4%). The majority of patients received combination therapy for the duration of Radium-223 treatment. Furthermore, 17.6% started another agent after Radium-223 initiation and 17.6% initiated Radium-223 while on an established therapy. Median OS from Radium-223 initiation was 12.4 months (95% CI 10.2, 13.9):
The median OS from first mCRPC treatment was slightly longer for patients with Radium-223 pre- vs. post-chemotherapy (by 2 months) and for patients with Radium-223 combination versus monotherapy (by 3 months).
Several limitations were noted by Dr. McKay:
- Data for this study were collected retrospectively and limited to data captured in medical charts
- Due to the descriptive nature of the study, OS analyses were not adjusted for the use of other life-prolonging mCRPC treatments in this population that may have influenced OS estimates
- Results reported in this study are based on data collected at one cancer referral center and may not be reflective of practice patterns observed in other institutions
Several conclusions from this Radium-223 tertiary referral center analysis:
- Radium-223 improves OS in mCRPC, and the longest OS was seen in those with Radium-223 pre-chemotherapy
- Retrospective analysis of 5 years of Radium-223 treatment data from an academic center demonstrates that patients treated pre-chemotherapy on average obtained one additional cycle of Radium-223, subsequent chemotherapy administration was not limited, and OS measured from first mCRPC therapy was not significantly different
- Additional studies are needed to determine the optimal sequencing strategy of mCRPC involving Radium-223 in the modern era
Presented by: Rana R. McKay, MD, Medical Oncologist, Assistant Professor of Medicine, UC San Diego Health
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