Retreatment With Radium-223 in Patients With Castration-Resistant Prostate Cancer and Bone Metastases

[Balsam01]

TAKE-HOME MESSAGE

•Radium-223 is approved for patients with castration-resistant prostate cancer and symptomatic bone metastases. Repeat treatment after initial therapy has not been studied. The authors studied 44 patients who completed an initial course of six Xofigo treatments without progression and then were retreated based on subsequent disease progression. All six retreatments were completed in 29 of the patients, and no new safety signals were observed. During the 2-year follow-up, 43% of patients progressed or died, with 11% of patients having bone progression. Median survival was 24 months.

•Based on these data, repeat treatment with radium in patients already treated is safe and appears to provide additional benefit in men with castration-resistant prostate cancer and bony disease.

– Gautam Jayram, MD

BACKGROUND

Radium-223 dichloride (radium-223) is approved for patients with castration-resistant prostate cancer (CRPC), symptomatic bone metastases, and no visceral disease using a dosing regimen of 6 injections (55 kBq/kg intravenously; 1 injection every 4 weeks). Early results from international, open-label, phase 1/2 study NCT01934790 showed that re-treatment with radium-223 was well tolerated with favorable effects on disease progression. Here we report safety and efficacy findings from 2-year follow-up of the radium-223 re-treatment study.

METHODS

Patients with CRPC and bone metastases who completed 6 initial radium-223 injections with no disease progression in bone and later progressed were eligible for radium-223 re-treatment (up to 6 additional radium-223 injections), provided that hematologic parameters were adequate and chemotherapy had not been administered after the initial course of radium-223. Concomitant cytotoxic agents were not allowed during re-treatment but were allowed at the investigator's discretion during follow-up; other concomitant agents for prostate cancer (including abiraterone acetate or enzalutamide) were allowed at investigator's discretion. The primary objective was safety. Exploratory objectives included time to radiographic bone progression, radiographic progression-free survival (rPFS), time to total alkaline phosphatase (tALP), and prostate-specific antigen (PSA) progression, overall survival (OS), time to first symptomatic skeletal event (SSE), and SSE-free survival, all calculated from re-treatment start. Evaluation of safety and exploratory efficacy objectives included active 2-year follow-up. Safety results from active follow-up and updated efficacy are reported.

RESULTS

Overall, 44 patients were re-treated with radium-223; 29 (66%) completed all 6 injections, and 34 (77%) entered 2-year active follow-up, during which no new safety concerns and no serious drug-related adverse events were noted. rPFS events (progression or death) occurred in 19 (43%) of 44 patients; median rPFS was 9.9 months. Radiographic bone progression occurred in 5 (11%) of 44 patients. Median OS was 24.4 months. Median times to first SSE and SSE-free survival were 16.7 and 12.8 months, respectively. Median time to tALP progression was not reached; median time to PSA progression was 2.2 months.

CONCLUSIONS

Re-treatment with radium-223 in this selected patient population was well tolerated, led to minimal hematologic toxicity, and provided continued disease control in bone at 2-year follow-up.

The Prostate

Re-Treatment With Radium-223: 2-Year Follow-up From an International, Open-Label, Phase 1/2 Study in Patients With Castration-Resistant Prostate Cancer and Bone Metastases

Prostate 2019 Oct 01;79(14)1683-1691, O Sartor, D Heinrich, N Mariados, MJ Méndez Vidal, D Keizman, C Thellenberg Karlsson, A Peer, G Procopio, SJ Frank, K Pulkkanen, E Rosenbaum, S Severi, J Trigo, L Trandafir, V Wagner, R Li, LT Nordquist

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

[Fairwind]

R-223 would become an obsolete treatment overnight if Lu-177 is approved.. Of course, price of treatment would enter the picture at this point..