Radium-223 treatment may be appropriate for first- or second-line therapy in men with metastatic castration-resistant prostate cancer (mCRPC), according to a new study.

In a study of 63 men with mCRPC who underwent radium-223 treatment, the median overall survival (OS) time was 15 months for the entire cohort but 23 months for men who received the drug as first-line therapy, investigators reported in Scientific Reports.

Radium-223 is an alpha-emitting bone-seeking radioisotope indicated for use in men with mCRPC and symptomatic bone metastases.

In the study, which was conducted by Elisa Lodi Rizzini, MD, and colleagues at DIMES University of Bologna in Bologna, Italy, radium-223 was administered as first-line therapy to 11 patients, second-line therapy to 19 patients, third-line therapy to 16 patients, and in successive lines to 17 patients. Each man received radium-223 (55 kBq/kg) every 4 weeks for up to 6 cycles. Patients had a median age of 76.8 years, and more than 50% had comorbid heart disease.


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Of the 63 patients, 42 (67%) completed all 6 cycles. Within 1 month after the end of 6 cycles, 35.7% of men had achieved a partial response, 26.2% had stable disease, and 33.3% had progressive disease. Pain levels diminished with each successive cycle.

The most frequent treatment-related toxicity was low-grade hematologic toxicity (predominantly G1-G2), which developed halfway through treatment in about 75% of men. “Our most considerable finding is the fact that anemia seems to be more the expression of advanced disease than an adverse effect of radium-223 therapy,” Dr Lodi Rizzini, a radiation oncologist, told Renal & Urology News. Patient treated early with supportive care (iron supplementation and/or blood transfusions) were able to complete radium-223 treatment with higher hemoglobin levels and less painful symptoms.

“In our opinion, the best candidate for the therapy is the patient with higher hemoglobin levels, lower levels of osteoporosis, and with oligometastatic disease,” Dr Lodi Rizzini said. “Our take-home message, in contrast with the current guidelines, is that early treatment with radium-223 with an early supportive care (iron and anti-resorptive bone-active drugs) can significantly improve quality of life by avoiding skeletal events as well as prolong overall survival.”

In the current study, 52 (82.5%) of the 63 men had received at least 1 line of systemic therapy and 33 (52.4%) had received 2 lines of systemic therapy, most commonly abiraterone and cabazitaxel before starting radium-223.

Kelvin A. Moses, MD, PhD, Associate Professor of Urology at Vanderbilt University Medical Center in Nashville, Tennessee, said while radium 223 was approved for men with symptomatic bone metastases in the setting of CRPC based on results from the ALSYMPCA trial, much is unknown about which patients may benefit the most. “Its role earlier in the disease process is unknown, as is the optimal sequence of therapy for men with mCRPC,” Dr Moses said. “This study in a small population of patients suggests that radium 223 as first-line or second-line treatment may be feasible. The results from this retrospective study would need to be confirmed in a randomized trial of radium-223 versus chemotherapy or second-generation antiandrogen as first-line therapy.”

“This study is not big enough to change clinical practice,” said Brent Hollenbeck, MD, Associate Professor of Urology at the University of Michigan in Ann Arbor, noting that although the findings are intriguing, the study is limited by its small sample size. “From a patient perspective, I think it may be a hard sell as first-line therapy over one of the oral agents since the majority of patients did not respond.” 

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Judd W. Moul, MD, Professor of Surgery in the Division of Urologic Surgery at Duke Cancer Institute in Durham, North Carolina, said because the study is a small single-center its value is limited. Further, he said radium-223 has fallen out of favor due to the safety issues of using it with abiraterone. “The death rate was higher when patients received radium-223 plus abiraterone, and this put the use of this agent into a tailspin,” Dr Moul said.

It might be better to sequence radium-223 earlier in the course of the disease so that patients are not so “beat up” from other therapies or their cancer when they get it, he said. “If a man is too far gone when he is prescribed radium 223, he will not be able to get the full course of 6 cycles,” Dr Moul said. “Without 5 to 6 cycles, there is felt to be no survival benefit. In this study, it is noteworthy and good that 67% of the study cohort were able to get all 6 cycles.”

Phuoc T. Tran, MD, PhD, Professor of Radiation Oncology and Molecular Radiation Sciences at Johns Hopkins Medicine in Baltimore, said the new findings raise interesting issues involving the use of radium-223 earlier rather than later. “Sequencing of the life prolonging agents in the mCRPC space, of which radium-223 is one, has been and continues to be one of the most critical questions in the treatment of mCRPC. Another question of clinical importance are combination approaches, and given recent data, these are best answered in a prospective clinical trial fashion.”                                        

Reference

Rizzini EL, Dionisi V, Ghedini P et al. Clinical aspects of mCRPC management in patients treated with radium-223 [published online April 21, 2020]. Sci Rep 10:6681 (2020). https://doi.org/10.1038/s41598-020-63302-2

This article originally appeared on Renal and Urology News