ZYTIGA (Abiraterone) and XTANDI (enzalutamide) are standards of care options for the first line mCRPC patients progressing on androgen deprivation therapy (ADT). No combination has been so far approved to increase the radiological progression-free survival (rPFS) and overall survival (OS) in first-line mCRPC.  

Data from a Phase III PEACE-3 (NCT02194842) comparative study of enzalutamide vs a combination of Radium-223 (Ra223) investigating whether the combination improves cancer progression over enzalutamide alone in patients with mCRPC was presented in the Proffered Paper Session at the ESMO 2024. 

With a median follow-up of 42.2 months, 87.9% of patients in the enzalutamide-radium-223 arm completed the planned six cycles of Ra223. The median rPFS was 16.4 months in the enzalutamide arm and 19.4 months in the combo arm. In a preplanned interim analysis, the median OS was 35.0 months and 42.3 months in the enzalutamide alone and combo arm, respectively.

The safety profile obtained is given below in the table.

KOL insights

"The HR for OS was also 0.69 with a statistically significantly positive p value. Due to the non-proportional hazards, it was recommended to continue to the final OS analysis despite this positive result, to confirm the observed treatment effect. Time to next systemic treatment was also statistically significantly prolonged in the combination arm." –MD, United States.

“Importantly, OS seems to be improved with enzalutamide plus Ra-223, with an approximately 30% reduction in risk of progression or death, and the analysis also showed acceptable safety for the combination. For clinicians who normally reserve ARPIs for mCRPC, the PEACE-3 results provide evidence of a new and more efficacious treatment option for earlier-stage disease.” –Prof. University of Paris Saclay, France

Conclusion 

Other therapies such as PARP inhibitors, immune checkpoint inhibitors, and combination regimens involving novel hormonal therapies and targeted agents are rapidly gaining ground. The evolving landscape suggests a shift toward more personalized and combination-based approaches in mCRPC, making it essential for Radium-223 and enzalutamide to secure a niche for specific patient subsets.

Despite being used for decades in the palliative treatment of prostate cancer, recent times have seen a revival in interest in radiopharmaceuticals. The Phase III PEACE-3  data presented at the ESMO 2024 showed that the addition of XOFIGO to XTANDI yielded significant improvements in rPFS and OS in patients with mCRPC and predominant bone metastases, and supports the combination as a potential new first-line mCRPC treatment option. The combination of ENZ and 6 cycles of Ra233 showed a statistically significant improvement in rPFS, with median rPFS increased from 16.4 months with ENZ to 19.4 months.

Other ongoing research into different radioisotopes and different targets will offer new hope for future treatments. 

For more insight into the patient's burden/epidemiology, treatment, and changing market landscape-related advancements, refer to the:

• Metastatic Castration-Resistant Prostate Cancer (mCRPC) - Market Insight, Epidemiology, And Market Forecast - 2032 report.
• Prostate Cancer Market Insight, Epidemiology, and Market Forecast -2034
• Metastatic Castration-Sensitive Prostate Cancer (mCSPC) - Market Insight, Epidemiology And Market Forecast - 2034