Real-World Analysis Supports Upfront Use of Radium-223 in mCRPC

Rana R. McKay, MD

Rana R. McKay, MD

Patients with metastatic castration-resistant prostate cancer (mCRPC) may benefit more from the use of radium-223 dichloride (Xofigo) when given before chemotherapy compared with post-chemotherapy, according to results from a retrospective analysis presented at the 2020 Genitourinary Cancers Symposium.

Included in the analysis were 220 patients who received radium-223 pre-chemotherapy (n = 64), post-chemotherapy (n = 83), or in the absence of chemotherapy (n = 73). Patients received a median of 5.3 and 4.3 injections of radium-223 in the pre- and post-chemotherapy cohorts, respectively (P <.001).

“There have been some data to suggest that if you give radium-223 pre-chemotherapy, patients’ counts may not be sustained, or they may not be able to receive every cycle of chemotherapy. However, the use of radium-223 before chemotherapy did not influence the amount of chemotherapy that patients could receive,” said lead study author Rana R. McKay, MD. “It was also more likely for a patient to complete all 6 cycles of radium-223 if it had been given first.”

Although radium-223 is approved for use as a single agent, the analysis also showed that 41.8% of patients received the radiopharmaceutical in combination with another agent, most commonly abiraterone acetate (Zytiga; 43.5%) or enzalutamide (Xtandi; 52.2%).

The median OS among all patients measured from the start of radium-223 was 12.4 months (95% CI, 10.2-13.9). Additionally, there was a 2-month improvement in median overall survival (OS) from patients’ initial therapy for mCRPC in those who received radium-223 pre-chemotherapy versus post-chemotherapy, at 39.4 months (95% CI, 33.0-48.8) and 37.4 months (95% CI, 32.0-43.5), respectively. Patients who received combination therapy experienced a 3-month improvement in median OS versus those who received radium-223 alone, respectively, at 35.2 months (95% CI, 27.9-43.3) and 32.0 months (95% CI, 26.9-36.0).

In an interview with OncLive, McKay, an assistant professor of medicine and medical oncologist at the University of California, San Diego, discussed the results of the real-world analysis with radium-223 and other exciting research in the mCRPC field.

OncLive: Could you provide some background on the trial?

McKay: Radium-223 is a liquid radiopharmaceutical that has been shown to improve survival for patients with advanced prostate cancer. It's specifically used for patients who have bone metastases, those who may have symptomatic bone pain, and those who don't have visceral metastases.

Results from the phase III ALSYMPCA trial demonstrated an improvement in OS with the agent. However, there hasn’t really been a lot of real-world data documenting how this agent is used in the changing landscape of advanced RCC. Since the ALSYMPCA trial, we have seen the approvals of several androgen receptor (AR)—targeted agents. We could potentially see PARP inhibition in the future. Placing radium-223 in that landscape in the context of the real-world has not been established. The rationale for this study was to characterize the utilization of radium-223 within real-world practice.

What did the results of the study show?

We included 220 patients who had received radium-223 between 2013 to 2017. We wanted to look at the characteristics of patients who had received radium-223 pre-chemotherapy versus post-chemotherapy. About half of patients had received radium pre-chemotherapy and half post-chemotherapy.

The median number of chemotherapy cycles when radium-223 was given before or after chemotherapy was 9 in both groups.

We also showed that if radium-223 was given pre-chemotherapy as opposed to post-chemotherapy, it was more likely that any individual patient would be able to complete all 6 cycles of radium-223. It’s given intravenously every 4 weeks for up to 6 doses.

What are the main implications of these findings?

[The biggest implication is regarding] the placement of radium-223. The trial wasn’t meant to look at the right sequence [of treatment]. [Instead it showed] that there's not really an increase in toxicity or a decline in the amount of chemotherapy that patients can receive if they receive radium-223 first.

In addition to evaluating radium-223 in the context of line of therapy, we also characterized how many people received radium-223 as a single agent and in combination in the real-world setting. It seems like approximately 40% of patients received radium-223 in combination with an AR-targeting agent, the majority of which was enzalutamide. That’s not necessarily an on-label use of radium-223, but in the real-world practice, we see concurrent AR-targeted agents.

With the ERA-223 data, it's important to stress the importance of using a bisphosphonate or bone-strengthening agent when radium-223 is used [to reduce] the risk of fragility fractures. Our study showed how we utilize radium-223 in the real world, and it provided some instruction to clinicians around the placement of radium-223 for patients with mCRPC.

How did patients tolerate radium-223? Were any new safety data reported?

In patients who received radium-223 after docetaxel, the median number of cycles received was 5 as opposed to 6. More patients were not able to complete the radium-223 when it was given after chemotherapy, whether that’s because of blood counts or disease progression.

Could you shed light on other real-world analyses that are being conducted with radium-223?

There has been a lot of excitement around the DNA repair pathway in prostate cancer. Since radium-223 is a liquid radiopharmaceutical, specifically an alpha particle that induces DNA damage in cells within the bone niche, we have to think about potential synergy in the context of those who have homologous recombination deficiency (HRD). Based on this data set, [we’ll be] looking at outcomes in patients with HRD-mutated versus [HRD]-nonmutated patients.

What were some of the key takeaways from the 2020 GU Cancers Symposium in prostate cancer?

If we hear the word “prostate-specific membrane antigen” (PSMA) one more time, I think everybody's will go crazy. PSMA imaging and PSMA-targeted therapies are really where the field is going. Everyone is anticipating the results of the VISION trial, which looked at Lutetium-177 PSMA in patients with advanced prostate cancer. That trial has the potential to have a profound impact on mCRPC treatment.

Quality of life (QOL) data were presented from the STAMPEDE trial, which evaluated abiraterone acetate versus docetaxel. It was interesting to see the patient-reported QOL analyses. Now that our patients are living longer, [we have to think about] how we can help them live better. That’s a huge takeaway.

McKay RR, Silver R, Bkak R, et al. Real-world utilization of radium-223 (Ra-223) for the treatment of metastatic castration-resistant prostate cancer (mCRPC): a U.S. tertiary oncology center analysis. J Clin Oncol. 2020;38(suppl 6; abstr 223). doi: 10.1200/JCO.2020.38.6_suppl.223