Long-term Data Show Ra-223 Safe in Advanced Prostate Cancer

Roxanne Nelson

January 31, 2014

San Francisco — The novel radiopharmaceutical radium-223 (Xofigo, Algeta/Bayer) appears to have long term safety with minimal adverse events.

In an updated report of the ALSYMPCA trial, no major safety issues were identified within ~1.5 years after the end of treatment in a population of men with castration-resistant prostate cancer (CRPC) and bone metastases.

The drug, which has been approved in both the US and the European Union, extended survival in this population and addressed an "important unmet need," according to researchers who initially reported the results of the phase 3 trial that led to the product's approval.

The updated results were presented here at the 2014 Genitourinary Cancers Symposium (GUCS).

"We found that it has a very benign safety profile, and that was shown in the earlier phase I and phase II trials," said lead author Sten Nilsson, MD, PhD, professor of oncology at the Karolinska Hospital, Stockholm, Sweden. "Now it is important that we try to follow the patients, and to see if any adverse events have developed and can be considered treatment related."

He told Medscape Medical News that they have been following both hematologic and nonhematologic side effects, as well as the possible induction of secondary malignancies.

Thus far, they have not seen any cases of myelogenous leukemia, myelodysplastic syndrome, or primary bone cancer, he continued. "We feel that it is important to follow up on adverse events, and so far, Radium-223 has a very benign profile."

The prognosis for this disease is poor, but radium-223 did extend survival. "The median survival was less than 1 year in placebo and 14.9 months in the active treatment arm, so the survival benefit was 3.6 months," Dr. Nilsson said. "That is a very robust finding."

He noted that they will continue to follow the surviving patients, and updated study results will be presented in the spring, at the annual meeting of the American Society of Clinical Oncology.

Improved Survival

The ALSYMPCA trial involved 921 men with CRPC and at least 2 bone metastases but no visceral metastases. Patients were enrolled whether or not they had received previous docetaxel therapy.

The trial was halted early after an interim analysis showed that treatment with radium-223 significantly improved survival as compared with placebo. When these early results were originally presented, they were hailed by experts as practice-changing and were considered a new standard of care.

The updated analysis has confirmed a median survival advantage of radium-223 over placebo (14.9 vs 11.3 months; hazard ratio, 0.70; P < .001).

The ALSYMPCA safety population included 901 patients (Ra-223, n = 600; placebo, n = 301). Overall, 25 (4%) of Ra-223 and 8 (3%) of patients on placebo experienced ≥ 1 treatment-related adverse event. During this follow-up, primary cancer in other organs was reported in 5 patients (Ra-223, n = 2; placebo, n = 3).

"There were cancers reported in other organs, but none were deemed to be associated with radium-223," Dr. Nilsson said.

The most common hematologic event was anemia, reported in 11 patients who received radium-223 (5 were grade 3/4) and in 5 patients in the placebo arm (1 grade 3/4). There was also one case of aplastic anemia, in a patient who received active treatment.

Unanswered Questions

There is now safety data for a year and a half, commented Michael J. Morris, MD, a medical oncologist from Memorial Sloan-Kettering Cancer Center, who was a discussant for the paper.

"For those concerned about long term bone marrow toxicity, it looks like one can rest easy and there are no surprises coming down the pipe," he said. "It prolongs survival and with a side effect profile that is tantalizingly close to zero."

But he noted that now that 1.5 years have passed, it is time to delve more deeply into finding out how the drug works, as much remains unclear.

For example, it does seem that "one can go much higher on the dose and still not risk toxicity," he said. "We don't know how to leverage the gains with this drug as monotherapy into combinations with other treatments."

"We also don't know how to identify a responder or progresser on this drug," Dr. Morris continued.

And perhaps the most frustrating aspect, from a scientific standpoint, is that "we don't know what the target is," he pointed out.

"What we do know is that it prolongs survival and we do know that at least at one and a half years out it is relatively safe, but there are many questions that need to be answered," he said.

Several of the authors report relationships with industry.

2014 Genitourinary Cancers Symposium (GUCS): Abstract 9. Presented January 30, 2014.

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