Follow-up Confirms Safety of Radium-223 in mCRPC

January 31, 2014

Conference | Genitourinary Cancers Symposium (ASCO GU)

Extended follow-up of patients with castration-resistant prostate cancer (CRPC) and bone metastases randomized to radium-223 dichloride (Xofigo) in the phase III ALSYMPCA study revealed a continued low incidence of myelosuppression and no association with secondary malignancies.

Sten Nilsson, MD

The ALSYMPCA study compared the efficacy and safety of radium-223 with placebo in 921 patients with CRPC and symptomatic bone metastases, demonstrating a 3.6-month improvement in overall survival in the radium-223 arm. The incidence of hematologic adverse events at the 2-year follow-up was low in the radium-223 group.

“What we found in the ALSYMPCA trial, and also in the phase I and II trials, is that radium-223 has a very benign safety profile, but I think it’s important to find out if this benign safety profile exists in the long-term follow-up,” said Nilsson, professor of Oncology at the Karolinska University Hospital in Stockholm, Sweden. “It could be that a new drug could give rise to second malignancies or new disease.”

The safety population consisted of 901 of the 921 patients enrolled in ALSYMPCA. Of the 901 participants in the safety analysis, 571 (404 randomized to radium-223 and 167 randomized to placebo) entered a designated long-term follow-up that lasted until 3 years after their first injection of radium-223. Eighty-three percent of the radium-223 group and 71% of the placebo group who entered the follow-up period completed all 6 injections of the study treatment.

The median follow-up durations at the time of the analysis (about 1.5 years after the patient’s last injection) were 10.4 months in patients randomized to radium-223 and 7.6 months for placebo recipients.

“The very benign safety profile we saw in previous studies and the ALSYMPCA study remained,” said Nilsson. “There were very few side effects with respect to hematologic parameters and also with non-hematologic parameters.”

Treatment-related adverse events reported during follow-up occurred in 25 of the 404 radium-223 patients (6%) and 8 of the 167 placebo patients (5%). The most common adverse events in the radium-223 group were hematologic: anemia (3%), aplastic anemia (<1%), leukopenia (<1%), neutropenia (1%), and thrombocytopenia (1%). Grade 3/4 hematologic adverse events in the radium-223 cohort included anemia (1%), aplastic anemia (<1%), leukopenia (<1%), and neutropenia (1%).

The one patient with aplastic anemia in the radium-223 group was diagnosed based on bone marrow biopsy. This patient had been treated previously with chemotherapy and repeated external beam radiotherapy due to bone metastatic disease, said Nilsson. Three percent of the placebo group experienced anemia and 1% had grade 3/4 anemia.

There were no reports of acute myelogenous leukemia, myelodysplastic syndrome, or primary bone cancer. Primary cancers in other organs developed in two radium-223 patients and three placebo patients, and were deemed by the investigators not to be related to the study drug.

Non-hematologic toxicities were rare in the radium-223 group, with the most common occurring in <1% of patients for each adverse event (general physical health deterioration, multiorgan failure, pneumonia, weight loss, anorexia, musculoskeletal pain, pathologic fracture, dizziness).

“Radium-223 is a good drug that prolongs life and the safety profile is very benign and keeps being so,” Nilsson said. The findings support the evaluation of combining radium-223 with other agents for the treatment of patients with CRPC and symptomatic bone metastases.

The full 3-year follow-up data will be presented at the 2014 meeting of the American Society of Clinical Oncology in Chicago in June.

Nilsson S, Vogelzang NJ, Sartor AO, et al. 1.5-year post-treatment follow-up of radium-223 dichloride (Ra-223) in patients with castration-resistant prostate cancer (CRPC) and bone metastases from the phase 3 ALSYMPCA study. J Clin Oncol. 2014;32(suppl 4; abstr 9).

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