Randomized Phase II Study Evaluating the Addition of Pembrolizumab to Radium-223 in Metastatic Castration-resistant...

Area of Science:

• Oncology
• Immunotherapy
• Radiopharmaceuticals

Background:

• Pembrolizumab shows limited efficacy in metastatic castration-resistant prostate cancer (mCRPC).
• Radium-223 may enhance anti-tumor immunity and pembrolizumab activity in mCRPC bone metastases.

Purpose of the Study:

• To evaluate the combination of Radium-223 and pembrolizumab in mCRPC.
• To assess the impact on tumor immune infiltration, safety, radiographic progression-free survival (rPFS), and overall survival (OS).

Main Methods:

• A randomized phase II study comparing Radium-223 plus pembrolizumab (R223+P) versus Radium-223 alone (R223).
• Analysis of CD4+ and CD8+ T-cell infiltrate in bone metastasis biopsies.
• Evaluation of safety, rPFS, and OS.

Main Results:

• No significant differences in CD4+ or CD8+ T-cell infiltration were observed between R223+P and R223 groups.
• Median rPFS and OS were similar for both treatment arms (R223+P: 6.1 months rPFS, 16.9 months OS; R223: 5.7 months rPFS, 16.0 months OS).
• The combination R223+P was well-tolerated, with no unexpected toxicity. R223+P induced CTLA-4 expression on circulating CD4+ T cells, but minimal immune modulation by R223 alone.

Conclusions:

• The combination of Radium-223 and pembrolizumab did not improve efficacy in patients with mCRPC.
• The combination therapy was safe but did not enhance tumor immune infiltration.
• Peripheral T-cell exhaustion may limit the clinical activity of this combination.