Genitourinary Cancer

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SU_28_2283 - Radium-223 for Men with Pretreated Metastatic Castrate Resistant Prostate Cancer, Too Little Too Late?

Sunday, October 21
1:15 PM - 2:45 PM
Location: Innovation Hub, Exhibit Hall 3

Radium-223 for Men with Pretreated Metastatic Castrate Resistant Prostate Cancer, Too Little Too Late?
R. Kalash1, Z. D. Horne2, R. P. Smith2, C. E. Champ1, L. Appleman3, and S. Beriwal4; 1Department of Radiation Oncology, Hillman Cancer Center, University of Pittsburgh School of Medicine, Pittsburgh, PA, 2Department of Radiation Oncology, UPMC Hillman Cancer Center, University of Pittsburgh School of Medicine, Pittsburgh, PA, 3Department of Medical Oncology, UPMC Hillman Cancer Center, University of Pittsburgh School of Medicine, Pittsburgh, PA, 4UPMC Hillman Cancer Center, Pittsburgh, PA

Purpose/Objective(s): Radium-223 (Ra-223) has demonstrated improved symptom, skeletal event (SSE), and survival outcomes in patients with bone-only metastatic castrate-resistant prostate cancer (mCRPC). Since publication of the ALSYMPCA study multiple therapeutic options have emerged for mCRPC, with no widely agreed upon sequence. Herein we report the outcomes of mCRPC patients pre-treated with multiple agents before initiation of Ra223.

Materials/Methods: A single-institution retrospective chart review identified consecutive patients with mCRPC treated with ≥ 1 course of Ra-223. Each infusion was delivered once/month for a maximum of 6 courses. Collected clinical outcomes included biochemical control, radiographic progression, SSE, and overall survival (OS).

Results: A total of 73 mCRPC cancer patients treated from 2013-2017 were identified. At baseline patients had a median Gleason score of 8, PSA of 31.9 ng/mL, and prior therapy duration of 28 months. A minority of patients (11/73, 15%) received Ra-223 following ALSYMPCA trial inclusion criteria of androgen deprivation therapy (ADT) +/- chemotherapy failure. The remaining ALSYMPCA-excluded patients, 62/73 (85%), received Ra-223 after failing a combination of ADT + second generation anti-testosterone (anti-T) therapy +/- chemotherapy. The entire cohort had a median follow up of 4 months, received a median of 5 Ra-223 cycles, and had a median overall survival of 6.6 mos following treatment. ALSYMPCA-appropriate patients received a median of 6 Ra-223 cycles and had a median overall survival of 11.2 months. ALSYMPCA-excluded patients received a median of 5 Ra-223 cycles, and had a median overall survival of 5.1 months. Factors predictive of completing 6 cycles of Ra-223 therapy were longer duration of prior therapy (p=0.08), lower pre Ra-223 PSA (0.06), concurrent therapy to Ra-223 (p=0.03), and prior definitive local therapy (p=0.06). Median survival was predicted by completion of 6 cycles of Ra-223 (13.6 vs. 2.1 mos, p<0.01) and higher pre Ra-223 PSA (9.7 mos (PSA > median) vs 3.7 mos (PSA < median), p=0.005). PSA failure occurred in 52/73 (71%) patients at a median of 1.6 mos following Ra-223. SSE occurred in 26/73 (36%) patients at median of 7.7 mos. Radiographic progression occurred in 20/73 (27%) patients. Completion of 6 cycles of Ra-223 and ALSYMPCA-appropriate criteria were predictive of 1-year PSA control (37.5% vs 10.7%, p=0.06) and SSE. Treatment was discontinued in 39/73 patients (53%), secondary to progressive pain in 15 (20%), radiographic progression in 11 (15%), toxicity in 11 (15%), and biochemical progression in 3 (4%) patients.

Conclusion: Ra-223 therapy provides expected outcome and tolerance in patients treated per ALSYMPCA-criteria, but poor survival in mCRPC patients treated after second generation anti-T therapy. Prospective studies are needed to provide guidance on the use of Ra-223 in the era of second generation anti-testosterone (anti-T) therapy as the benefit appears to be reduced.

Author Disclosure: R. Kalash: None. Z.D. Horne: None. L. Appleman: None. S. Beriwal: Consultant; Varian, XOFT. Editorial Board; Red Journal. Editorial Board; Brachytherapy Journal. Senior Editor; iJROBP.

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