7008 POSTER DISCUSSION Twenty-four-month Safety Data From Phase II Studies of Radium-223 Chloride, a First-in-class Alpha-pharmaceutical With a Highly Favorable Safety Profile for Patients With Castration-resistant Prostate Cancer (CRPC) and Bone Metastases

167 Background: The ALSYMPCA study was conducted to evaluate the alpha-emitting radiopharmaceutical Radium-223 Chloride (BAY 88-8223) in patients with symptomatic bone metastases in Castration resistant prostate cancer (CRPC). This trial met its primary endpoint of overall survival at the time of pre-planned interim analysis. Post hoc analysis showed a reduction from baseline in total ALP at 12 weeks (32% reduction in the BAY 88-8223 arm vs. 37% increase in placebo arm, P < 0.001) (Sartor et al. ASCO 2013). We are reporting here a single-arm, open-label, multicenter, phase II clinical study of BAY 88-8223 in Japanese patients with symptomatic CRPC with bone metastases. Methods: Eligible patients had progressive, symptomatic CRPC with at least 2 bone metastases on bone scintigraphy and no known visceral metastases; were receiving Best Standard of Care; and either had previously received docetaxel, were docetaxel ineligible, or had refused docetaxel. Patients received 6 injections of radium-223 (50 kBq/kg IV) every 4 weeks. The primary endpoint was percentage of change in total ALP from baseline at 12 weeks. Secondary endpoints included overall survival, time to symptomatic skeletal event, percentage of change in bone ALP/PSA/biomarkers, and safety. Results: A total of 67 subjects were enrolled; 18 were screening failures, and 49 were received to the study treatment and received at least one administration from September 2013 to May 2014. The mean percent change in total ALP from baseline at 12 weeks was -19.3% (95%CI: -28.0% to -10.7%). The results of secondary endpoints will be presented. The safety and tolerability profile for BAY 88-8223 were highly favorable and only 1 subject (2.0%) experienced lymphocyte count decreased as a Grade 4 adverse event, and there was no death during the study treatment and within 30 days after the last injection of study treatment. Conclusions: The reduction from baseline in total ALP at 12 weeks seen in this phase II study is consistent with the results shown in ALSYMPCA study. Overall, BAY 88-8223 was well tolerated in Japanese patients with CRPC and bone metastases. Clinical trial information: NCT01929655.

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Radium-223 in combination with enzalutamide in metastatic castration-resistant prostate cancer: a multi-centre, phase II open-label study

Therapeutic Advances in Medical Oncology ◽

10.1177/17588359211042691 ◽

2021 ◽

Vol 13 ◽

pp. 175883592110426

Author(s):

Raymond S. McDermott ◽

John Greene ◽

John McCaffrey ◽

Imelda Parker ◽

Sylva Helanova ◽

...

Keyword(s):

Prostate Cancer ◽

Bone Metastases ◽

Median Time ◽

Phase Ii ◽

Combination Treatment ◽

Bone Health ◽

Castration Resistant Prostate Cancer ◽

Clinical Progression ◽

Castration Resistant ◽

Radium 223

Background: Radium-223 and enzalutamide are approved agents for patients with metastatic castration-resistant prostate cancer (mCRPC). Combining radium-223 and enzalutamide to improve outcomes is of clinical interest due to their differing modes of action and non-overlapping toxicity profiles. Methods: This phase II study enrolled patients with mCRPC and bone metastases. Patients received six cycles of radium-223 in combination with enzalutamide, followed by enzalutamide alone. The primary endpoint was safety for the combination; secondary endpoints included radiographic/clinical progression-free survival (PFS), PSA PFS, overall survival (OS), change in alkaline phosphatase, patient-reported pain outcomes and skeletal related events. Results: Forty-five patients received the combination treatment: 42 patients (93.3%) received all six cycles. Fourteen patients (31.1%) developed grade 3 or 4 toxicities, most commonly fatigue and neutropaenia. Fractures during the combination period occurred in four patients (8.9%). A further 13 patients (28.9%) developed fractures after completing combination treatment, giving a total of 17 patients (37.8%) who developed a fracture at any time on study. The median time to fracture was greater than 17.2 months [95% confidence interval (CI), 17.2–not estimable]. The median time to PSA progression was 18.1 months (95% CI, 12.68–22.60) and the median time to radiological/clinical progression was 28.0 months (95% CI, 22.54–not reached). At the primary analysis, 19 (42.2%) out of 45 patients had died with a median OS not reached (mean 34.8 months, standard error 1.4). Conclusion: In men with progressive mCRPC and bone metastases, the combination of radium-223 and enzalutamide was tolerable with the majority of patients completing the combination treatment. Bone fractures during the combination period were uncommon; however, we did identify a higher incidence of fractures occurring in patients after completing combination treatment. Bone health agents should be administered and bone health should be closely monitored following treatment with radium-223 and enzalutamide.

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