• Reproductive Cancers
• Oncology Clinical Trials

• Reproductive Cancers
• Oncology
• Oncology Clinical Trials

Matthew R. Smith, MD, PhD, Massachusetts General Hospital, Boston, Massachusetts, USA, discussed the Phase III Randomized, Double-Blind, Placebo-Controlled Trial of Radium-223 Dichloride in Combination With Abiraterone Acetate and Prednisone/Prednisolone in the Treatment of Asymptomatic or Mildly Symptomatic Chemotherapy-Naïve Subjects With Bone Predominant Metastatic Castration-Resistant Prostate Cancer (CRPC) trial [ERA 223; NCT02043678] that is now recruiting patients with bone metastases and CRPC.

According to Dr Smith, skeletal metastases are common in prostate cancer, occurring in approximately 90% of men with advanced disease. Bone metastases result in decreased quality of life by causing problems such as bone pain, morbidity, pathologic fracture, and spinal cord compression [Autio K, Morris MJ. Clin Adv Hematol Oncol. 2013].

Although approximately half of patients with metastatic prostate cancer are asymptomatic and may not be good candidates for immediate chemotherapy, they may benefit from alternate therapies [National Comprehensive Cancer Network. Clinical Practice Guidelines in Oncology: Prostate Cancer v2. 2014; Cookson MS et al. Castration-Resistant Prostate Cancer: American Urological Association (AUA) Guideline. 2014].

A first-in-class α-radiopharmaceutical that selectively targets bone metastases, radium-223 has gained US Food and Drug Administration approval for use based primarily on increased overall survival (OS) demonstrated in the large, randomized, placebo-controlled phase 3 ALSYMPCA trial [Parker C et al. N Engl J Med. 2013; http://www.fda.gov/Drugs/InformationOnDrugs/ApprovedDrugs/ucm352393.htm].

Compared with placebo, radium-223 prolonged OS by 3.6 months and delayed time to first symptomatic skeletal event (SSE) by 5.8 months in patients with CRPC with symptomatic bone metastases when added to best standard of care [Parker C et al. N Engl J Med. 2013]. It also demonstrated a favorable safety profile with low rates of myelosuppression, which supports combining it with other agents, noted Dr Smith.

He added that abiraterone plus prednisone is a standard of care for patients with CRPC who are not eligible for docetaxel because they are asymptomatic or mildly symptomatic. Abiraterone produces OS and radiographic progression-free survival benefits, and significantly delays clinical deterioration and initiation of chemotherapy in patients with metastatic CRPC (mCRPC) [Ryan CJ et al. N Engl J Med. 2014].

According to Dr Smith, the different modes of action of radium-223 and abiraterone, and their non-overlapping toxicity profiles, suggest that a combination of the 2 treatment options will prolong SSE-free survival compared with abiraterone alone.

Consequently, ERA 223 was designed to prospectively evaluate combination therapy with abiraterone acetate and prednisone in combination with radium-223 in men with asymptomatic or mildly symptomatic, chemotherapy-naïve, bone-predominant mCRPC.

The study will accrue patients with bone metastases (both symptomatic and asymptomatic) and CRPC. It will include men (≥ 18 years with a life expectancy ≥ 6 months) with pathologically confirmed prostatic adenocarcinoma that is castration-resistant, with ≥ 2 bone metastases within 4 weeks prior to randomization.

Exclusion criteria include prior treatment with abiraterone or cytotoxic chemotherapy, and a history of visceral or brain metastasis.

Approximately 800 eligible subjects will be randomized 1:1 to abiraterone acetate (1000 mg QD) and oral prednisone (5 mg BID) plus radium-223 (50 kBq/kg body weight intravenously, every 4 weeks for 6 cycles) or abiraterone acetate and prednisone plus placebo.

The primary end points are SSE-free survival, with a key secondary end point of OS. In order to determine safety and OS, the long-term follow up consisted of a phone call every 6 months until 7 years after the last dose of radium-223 or death.

During the study, patients will be evaluated at each treatment visit for efficacy, safety, and health-related quality of life. Disease progression and long-term safety will also be assessed every 3 months. Upon completion of radium-223 treatment, all subjects will continue to receive abiraterone plus prednisone until occurrence of an SSE or death.

This trial is currently recruiting participants, with 74 enrolled as of September 5, 2014, concluded Dr Smith.

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