Bayer's Xofigo and Xtandi combination increases overall survival in mCRPC patients with bone metastases.

Bayer's Xofigo combined with Xtandi shows a significant increase in overall survival for patients with metastatic castration-resistant prostate cancer (mCRPC) and bone metastases. The Phase III PEACE-3 trial found a 24% reduction in death risk, improving median survival by 5.6 months.

Bayer's radioligand therapy, Xofigo (radium-223 dichloride), has shown significant efficacy when used in combination with Xtandi (enzalutamide) as a first-line treatment for patients with metastatic castration-resistant prostate cancer (mCRPC) who have bone metastases. These findings are based on results from a pivotal Phase III clinical trial.

PEACE-3 Trial Design and Outcomes

The results come from the open-label, investigator-initiated PEACE-3 study (NCT02194842), which compared the combination of Xofigo and Xtandi against Xtandi monotherapy. Key findings from the trial include:

• Patients receiving the Xofigo-Xtandi combination experienced a 24% reduction in the risk of death compared with those on Xtandi alone.
• The median overall survival (OS) reached 38.2 months for the combination group, representing a 5.6-month increase over the 32.6-month median OS observed in the Xtandi monotherapy group.
• Radiological progression-free survival (rPFS) improved to 19.4 months with the combination, compared with 16.4 months in patients receiving only Xtandi, meeting the trial's primary endpoint.

These results highlight the continuing significance of overall survival as a primary regulatory endpoint in oncology trials, confirming its status as a gold standard for assessing clinical benefit.

Safety and Adverse Events

The combination treatment demonstrated effectiveness but was associated with a higher rate of serious treatment-emergent adverse events (TEAEs). The safety data showed:

• 69% of patients in the combination group experienced Grade 3 or higher TEAEs.
• 58% of patients in the Xtandi monotherapy group experienced Grade 3 or higher TEAEs.
• No individual severe TEAE occurred in more than 5% of patients in the combination group compared with Xtandi alone.

Trial Sponsorship

The PEACE-3 trial was sponsored by the European Organisation for Research and Treatment of Cancer (EORTC), a non-profit organization dedicated to international translational and clinical research supporting evidence-based treatment decisions in oncology.

Radioligand Therapy in Oncology

Radiopharmaceuticals are increasingly incorporated into cancer treatment as alternatives to conventional chemotherapy. Radioligand therapies (RLTs) such as Xofigo and Pluvicto (lutetium Lu 177 vipivotide tetraxetan) have received approval in the United States for treating mCRPC, particularly in patients with prostate-specific membrane antigen (PSMA)-positive disease. Market analyses forecast that RLTs for prostate cancer may generate approximately $6.3 billion in revenue by 2030, primarily driven by Pluvicto sales.

Major pharmaceutical companies, including AstraZeneca, Eli Lilly, and Bristol Myers Squibb, have engaged in multi-billion-dollar mergers and acquisitions involving radiopharmaceutical-focused firms between 2023 and 2024. Investor interest is also increasing, with venture funding reaching $408 million in 2023 and a 330% growth in the first quarter of 2024 compared with the same period in 2023. Experts indicate that theranostics, which combine diagnostic and therapeutic capabilities, may become a key element in precision, image-guided oncology therapies.

Conclusion

The combination of Bayer's Xofigo with Xtandi offers a clinically meaningful improvement in overall survival for patients with mCRPC and bone metastases, while maintaining an acceptable safety profile. These results reinforce the expanding role of radioligand therapies in the treatment landscape for prostate cancer.

Sources:

• Enzalutamide/Radium‑223 Offers Long‑Term Gains in mCRPC - Oncology Nursing News
• Bayer's XOFIGO Plus Enzalutamide Reduces Death Risk by 24% in Metastatic Prostate Cancer Trial - MedPath
• Enzalutamide/Radium‑223 Extends Survival in mCRPC - CancerNetwork
• Radium‑223 Plus Enzalutamide Boosts Survival in Metastatic Prostate Cancer - OncologyNewsCentral
• Bayer’s Xofigo plus Xtandi extends OS in mCRPC with bone metastases