Concomitant Ra 223, abiraterone found safe, effective

April 1, 2016

Radium 223 dichloride (Ra 223 [Xofigo]) can be safely combined with abiraterone acetate (ZYTIGA) for the treatment of patients with metastatic castration-resistant prostate cancer with symptomatic bone metastases, and appears to result in decreased bone pain and improved quality of life, according to the interim results of an open-label prospective study known as eRADicAte.

San Francisco-Radium 223 dichloride (Ra 223 [Xofigo]) can be safely combined with abiraterone acetate (ZYTIGA) for the treatment of patients with metastatic castration-resistant prostate cancer (mCRPC) with symptomatic bone metastases, and appears to result in decreased bone pain and improved quality of life, according to the interim results of an open-label prospective study known as eRADicAte.  

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Both agents have been shown to prolong survival in this setting and are approved by the FDA for this indication, but the effect of combining them hasn’t been formally addressed in a prospective manner.

Dr. ShoreData from 30 evaluable patients in the study demonstrate an improvement in several significant subscales of quality of life and pain indices, no new safety concerns, no exacerbation of adverse effects beyond those reported with use of either agent by itself, and no serologic abnormalities of concern, said lead investigator Neal D. Shore, MD. He presented the interim data at the Genitourinary Cancers Symposium in San Francisco.

“To my knowledge, even though the numbers are not huge, this interim analysis represents the largest reported combination trial which has been conducted in a monitored prospective design,” said Dr. Shore, medical director, Carolina Urologic Research Center, Myrtle Beach, SC.

Some clinicians have been combining the two agents in practice without evidence from a prospective randomized clinical trial to support concurrent use, he noted.

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“When I received the grant to do this study, there were no data on combination therapy,” Dr. Shore said. “The first data that came out were from some of the early expanded access program reports of different types of combination treatment. But none of it was done in a prospective prespecified way.”

Next: How the study was conducted

 

His group conducted an open-label phase II study of patients with symptomatic bone mCRPC with no visceral metastases. The study was carried out at five sites nationally in medical oncology and urology clinics, providing “national geographic distribution, specialty distribution, and a real-world experience of using these two drugs on label for the similar population of patients who are M1 CRPC.”

Patients were treated with Ra 223 every 4 weeks x 6 doses, and concomitant abiraterone acetate, 1,000 mg, plus prednisone, 5 mg, twice daily. Patients could have received other prostate cancer treatments (ie, sipuleucel-T [Provenge], denosumab [XGEVA], or docetaxel [Taxotere]). The primary efficacy outcome was quality of life and bone pain assessments using the Brief Pain Inventory (BPI)-Short Form (SF) and Functional Assessment of Cancer Therapy-Prostate (FACT-P) questionnaires.

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Of the 36 patients enrolled, 30 received all six cycles of radum-223 and concurrent abiraterone acetate and thus were evaluable.

Next: Significant decrease in bone pain seen

 

Significant decrease in bone pain seen

There was a significant decrease in self-assessed average bone pain during the study period, from 3.0 at screening to 1.9 at the end of treatment (p=.014). From the BPI-SF scores, patients experienced no significant increase in how pain interfered with their daily lives. The amount of bone pain that interfered with mood (BPI mood rating) declined from 2.3 to 1.4 (p=.045), and the amount that interfered with work (BPI work rating) fell from 2.9 to 2.1 (p=.019) over the study period.

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“We wanted to see how patients would tolerate these two distinct mCRPC-approved therapies,” Dr. Shore said. “The mechanisms of action are very different. Radium-223 is a calcium mimetic; it goes to mineralization sites and effects double-stranded DNA breaks, as opposed to abiraterone acetate, which is working on the androgen biosynthesis pathway. There were no new findings regarding the respective safety profiles of either drug.”

There were no adverse laboratory values or serologic parameters affecting hemoglobin, albumin, white blood cell count, platelets, or transaminases.

Guidelines from the American Society of Oncology, AUA, and National Comprehensive Cancer Network (NCCN), among others, incorporate Ra 223 (level 1 evidence) for use in CRPC patients with bone metastases. In the NCCN guidelines, the use of Ra 223 after the first novel hormone is a level 1 recommendation.

Radiologic endpoints from eRADicAte will be presented later this year, said Dr. Shore.

Dr. Shore is a consultant/adviser for Astellas Pharma, Bayer, Ferring, Janssen Pharmaceuticals, Medivation, and Sanofi. His institution has received research funding from Bayer.

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