Circulating biomarkers are prognostic for radium-223 benefit in mCRPC

Circulating tumor cell (CTC) and automated bone scan index (aBSI) analyses may serve as potential biomarkers for survival among patients treated with radium-223 for metastatic castration-resistant prostate cancer (mCRPC), according to data published in JCO Precision Oncology.¹

The current study is the first to assess molecular RNA signatures in CTCs as potential prognostic biomarkers for radium-223 in mCRPC.

“Radium-223 is a valuable treatment option for patients with mCRPC, but better biomarkers are needed to identify patients most likely to benefit from therapy. This study suggests that CTC analysis may be a promising candidate for such circulating biomarkers,” said Annie Partisano, PharmD, MS, in a news release on the findings.² Patisano is the senior vice president and head of operations at TellBio, Inc, the developer of the TellDx CTC System.

Among all patients included in the study, the median overall survival (OS) was 21.3 months after treatment with radium-223.

Data showed that a lower aBSI at baseline was associated with improved OS, with patients that had a baseline aBSI of less than 0.9 experiencing a median OS of 39.9 months, compared with 15.2 months among those with a baseline aBSI of 0.9 or higher (HR, 5.874; 95% CI, 1.582-21.81; P = .00341). A minimal change in aBSI (less than +0.7) from baseline to 2 months was also associated with improved OS (P = .0139).

Further, a higher baseline CTC count of 5 CTC or more/7.5 mL at baseline was associated with worse OS. Specifically, patients with a higher baseline CTC count experienced a median OS of 10.1 months, vs 32.9 months among those with a lower CTC count (P = .00568). Patients with a CTC_M score (a panel of 8 prostate cancer-specific genes) of 20 or less experienced a median OS of 36.6 months, compared with 15.6 months among those with a CTC_M greater than 20 (HR, 5.874; 95% CI, 1.582-21.81; P = .00341).

Among the 15 patients with detectable baseline CTCs, 4 experienced declines in CTCs at 2 months. CTC decline was not associated with OS.

Additionally, among the individual genes in CTCs, significantly worse OS was seen with baseline expression of the splice variant AR-V7. Specifically, those with detectable baseline AR-V7 experienced a median overall survival of 11.8 months, compared with 31.1 months among those without detectable baseline AR-V7 (HR, 5.198; 95% CI, 1.657-16.31; P = .00195). No significant association was observed between the number of CTCs and the presence of AR-V7.

Baseline detectable AR-V7, higher aBSI, and a CTC count of 5 or higher/7.5 mL were all significantly associated with an independent negative impact on OS even after investigators controlled for prostate-specific antigen or total alkaline phosphatase levels. The presence of baseline CTC AR-V7 expression was found to be most predictive of OS.

Overall, the prospective study enrolled 22 patients with bone mCRPC who received treatment with standard radium-223 once monthly for up to 6 doses. Each patient underwent 99mTc-MDP bone scan imaging at baseline, 2 months, and 6 months, and the images were quantitated using aBSI. CTCs were assessed at baseline, 1 month, and 2 months for RNA expression of prostate cancer-specific genes. Isolation of CTCs was done using the TellDx CTC System.

Radium-223 was granted FDA approval in May 2013 for the treatment of patients with CRPC with symptomatic bone metastases and no known visceral proliferation.³ In the phase 3 ALSYMPCA trial (NCT00699751) that supported the FDA approval, radium-223 was shown to improve OS and reduce the time to first symptomatic skeletal event in patients with mCRPC.

The current study is the first to prospectively assess molecular RNA signatures in CTCs as potential prognostic biomarkers for radium-223, according to the news release on the findings.

“These results are encouraging and suggest that circulating biomarkers may be useful in guiding the use of radium-223 therapy,” concluded senior author David T. Miyamoto, MD, PhD, in the release.² Miyamoto is an assistant professor of radiation oncology at Harvard Medical School and an attending radiation oncologist at Massachusetts General Hospital in Boston.

References

1. Saylor PJ, Otani K, Balza R, et al. Circulating and imaging biomarkers of radium-223 response in metastatic castration-resistant prostate cancer. JCO Precis Oncol. 2024:8:e2300230. doi:10.1200/PO.23.00230

2. Tellbio’s technology demonstrates that analysis of circulating tumor cells can predict survival among patients with metastatic castration-resistant prostate cancer Receiving Radium-2230. News release. TellBio, Inc. Published online and accessed March 27, 2024.

3. Bayer receives US FDA approval for xofigo (radium Ra 223 dichloride) injection as a new treatment for castration-resistant prostate cancer with bone metastases. News release. May 15, 2013. Accessed March 27, 2024. https://www.prnewswire.com/news-releases/bayer-receives-us-fda-approval-for-xofigo-radium-ra-223-dichloride-injection-as-a-new-treatment-for-castration-resistant-prostate-cancer-with-bone-metastases-207545191.html