Three-year follow-up of a phase II study of radium-223 dichloride in Japanese patients with symptomatic castration-resistant prostate cancer and bone metastases

Abstract

Background Radium-223 is a first-in-class targeted alpha therapy to prolong overall survival (OS) in castration-resistant prostate cancer with bone metastases (mCRPC). The aim of the present analysis was to assess the long-term safety with radium-223 in Japanese patients with mCRPC. Methods Patients with symptomatic mCRPC, ≥ 2 bone metastases and no known visceral metastases received up to 6 injections of radium-223 (55 kBq/kg), one every 4 weeks. Adverse events (AEs) considered to be related to radium-223 were reported until 3 years after the first injection. Pre-specified conditions, such as acute myelogenous leukemia, myelodysplastic syndrome, aplastic anemia, primary bone cancer, or other primary malignancies, were reported regardless of causality. Results Of the 49 patients enrolled in the study, 44 (89.8%) entered the survival follow-up period and 33 (67.3%) died. Throughout the entire study, there were no reports of second primary malignancy or other pre-specified conditions. Eight patients (16.3%) experienced post-treatment drug-related AEs, which were all hematological (anemia and decreased lymphocyte, platelet, and white blood cell counts). No serious post-treatment drug-related AEs were reported. Updated median OS was 19.3 months (95% CI: 14.2, 28.5). Conclusions In Japanese patients with symptomatic mCRPC and bone metastases, radium-223 had a favorable long-term safety profile with no second primary malignancies reported. Taken together with median OS, which was comparable to that in the pivotal phase III ALSYMPCA study, these results support continued benefit from radium-223 in Japanese patients with mCRPC. Electronic supplementary material The online version of this article (10.1007/s10147-018-01389-4) contains supplementary material, which is available to authorized users.

Prognostic Value of the BIO-Ra Score in Metastatic Castration-Resistant Prostate Cancer Patients Treated with Radium-223 after the European Medicines Agency Restricted Use: Secondary Investigations of the Multicentric BIO-Ra Study

“…In the present analysis, we verified whether the prognostic power of the BIO-Ra score is still preserved in light of the EMA restriction of the use of Ra-223. Moreover, we verified the correlation between the BIO-Ra score and treatment completion, which is a well-known prognostic factor in mCRPC patients treated with Ra-223 [ 20 , 21 , 22 , 23 , 24 ].…”

“…This finding is coherent with the observed prediction of treatment completion by the BIO-Ra score in the same time interval. Indeed, several previous studies showed a substantial survival benefit in patients reaching the completion of Ra-223 cycles [ 20 , 21 , 22 , 23 , 24 ].…”

Quantifying the survival benefit of completing all the six cycles of radium-223 therapy in patients with castrate-resistant prostate cancer with predominant bone metastases

“…Two UK and a single Canadian studies looked at the effect of completing at least five cycles of treatment and similar to our results, there was a survival benefit but at 5-9 months was less than the 25 months we found in our patient group. [ 16 17 18 ] The reason for this difference is unclear but maybe related to difference in patient selection at different treatment centers. For example, it was a policy in our region to refer patients for radium-223, if suitable, as soon as they failed chemical castration or chemotherapy.…”

Dynamic changes of bone metastasis predict bone‐predominant status to benefit from radium‐223 dichloride for patients with castration‐resistant prostate cancer

“…7 Although Ra-223 can play a major role in the management of mCRPC and symptomatic bone metastasis, it remains unclear how to best employ this treatment in clinical practice. 8,9 Some patients have disease progression of non-bone metastasis with eventually elevated PSA levels during Ra-223 treatment, which can occasionally be too late for the patient to receive subsequent therapies. Thus, the diagnostic certainty of bone-predominant mCRPC needs to be determined.…”