Emerging Trials and the Future of Biomarker-Driven Therapy in Metastatic Castration-Sensitive Prostate Cancer

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Dr McKay discusses the exciting developments in biomarker-driven therapy for metastatic castration-sensitive prostate cancer (mCSPC), highlighting the AMPLITUDE trial’s success with abiraterone plus olaparib in patients with DNA damage response alterations. The study showed particularly pronounced benefits in patients with BRCA1/2 mutations, representing a significant step toward precision medicine in prostate cancer treatment. Similarly, the positive PSMA ADDITION trial news release suggests potential benefits of lutetium-177-PSMA-617 in PSMA-positive disease, although full results remain pending.

The increasing complexity of treatment options extends beyond PARP inhibitors to include the CAPITELLO study investigating capivasertib (AKT inhibitor) in PTEN-deficient patients with mCSPC. These targeted approaches require sophisticated patient selection based on molecular profiling, creating opportunities and challenges for clinical practice. The success of these biomarker-driven trials suggests a future where treatment decisions will be increasingly guided by tumor genetics rather than clinical factors alone.

Implementing precision medicine approaches in mCSPC will require significant changes in clinical practice, including routine molecular testing and multidisciplinary treatment planning. Questions remain about optimal sequencing of targeted therapies, long-term toxicity management, and impact on subsequent treatment options. As these novel agents undergo regulatory review, the field must prepare for a new era of personalized prostate cancer treatment that balances efficacy, toxicity, and quality-of-life considerations.