Daniel Heinrich, MD
Formal discussant of the ERA 223 trial, Daniel Heinrich, MD, of Akershus University Hospital, Lørenskog, Norway, reminded listeners at the European Society for Medical Oncology (ESMO) 2018 Congress that radium-223 was developed in Norway.
“When the ALSYMPCA results came out, we were celebrating. But now we have a negative trial—ERA 223—and we have to discuss the implications for our daily practice,” Dr. Heinrich said.
“The time to first skeletal-related event was within the range of expectation for AAP (abiraterone acetate [Zytiga] and prednisone)—26 months. But the assumption of 21 months for the control arm was too low by 4 to 5 months, based on other trials, so the trial would be negative, even with a 6-month prolonged symptomatic skeletal event–free survival, and my impression is that the trial never had a chance to show a statistically significant,” he commented.
“The excess of fracture is nothing new, and it mainly occurs within the first 12 months. Using bone health agents can prevent a proportion of fractures, but only 40% of patients were on bone health agents at the beginning of the trial,” Dr. Heinrich said.
“In the future, AAP plus radium-223 cannot be recommended as first-line [treatment],” he continued. “The concomitant addition of radium-223 to AAP vs enzalutamide (Xtandi) has never been tested in a prospective trial. Hence, ERA 223 results are not informative for this question. So when you go back home to your practice, carry on as before,” he said.
EMA Recommendation Questioned
As a result of the ERA 223 findings, the European Medicines Agency (EMA) recommended restricting the use of radium-223 to patients who have had 2 previous treatments for metastatic prostate cancer or who cannot receive other treatments. Dr. Heinrich took issue with this revised indication.
He pointed out that the EMA decision was based on a subgroup analysis of ALSYMPCA that showed no significant survival benefit associated with the use of radium-223 in patients with less than 6 bone metastases. In his view, the EMA “disregarded the overall survival advantage seen in ALSYMPCA in the intent-to-treat population, and the indication for radium-223 should be for patients with more than 6 bone metastases. I would like to see the EMA revoke and rethink this change in indications,” he stated.
He emphasized that bone health has to be strengthened in all patients with metastatic castration-resistant prostate cancer, not just those treated with radium-223. “Bone health needs more attention in our patients with metastatic castration-resistant prostate cancer, and bone health agents need to be used more regularly,” he stated.
Silke Gillessen, MD
Session Co-Chair Silke Gillessen, MD, of The Christie NHS Foundation Trust in Manchester, United Kingdom, agreed with both Dr. Heinrich and lead author Matthew R. Smith, MD, PhD. “Given the trial results, the combination of radium-223 plus AAP cannot be recommended. Bone health is an important issue in patients on androgen-deprivation therapy. We need to learn much more about it, and we have to take care of the bone health of our patients, as it is crucial to their quality of life,” Dr. Gillessen stated. ■
DISCLOSURE: Dr. Heinrich is an advisor for AstraZeneca, Bayer, Eisai, Ipsen, Janssen-Cilaq, and Roche; has received speaker honoraria from Astellas, Bayer, Bristol-Myers Squibb, Janssen-Cilaq, and Novartis; and has received research funding from Astra Zeneca, Bayer, Bristol-Myers Squibb, Janssen-Cilaq, Merck Sharp & Dome,and Roche. Dr. Gillesen is a consultant/advisor (including IDMC) with AAA International, Active Biotech, Astellas, Bayer, Bristol-Myers Squibb, CellSearch (Menarini Silicon Biosystems), Clovis, Curevac, Dendreon, Ferring, Innocrin, Janssen, MaxiVAX SA, Millennium, Novartis, Orion, Pfizer, Roche, and Sanofi; is on the speakers bureau of (compensated) Janssen and Novartis; and has a patent application for a biomarker method (WO 2009138392 A1).
The combination of radium-223 plus AAP (abiraterone acetate [Zytiga] and prednisone) was not superior to placebo plus AAP in the phase III ERA 223 trial, which enrolled men with asymptomatic bone-predominant metastatic castration-resistant prostate cancer.1 Patients treated with the combination had ...