New first-line treatment improves progression-free survival for select men with bone mCRPC

Abstract

Men with metastatic castration-resistant prostate cancer (mCRPC) treated with a combination of enzalutamide (ENZ) and the bone-protecting agent ²²³Ra (ENZ–RAD) showed significant improvement in radiological progression-free survival in comparison with those treated with ENZ alone according to the first results of the EORTC-GUCG-1333 (PEACE-3) trial presented at the 2024 European Society for Medical Oncology annual meeting in Barcelona.¹

Silke Gillessen Sommer, MD, head of the Medical Oncology Department and medical scientific director of the Oncology Institute of Southern Switzerland at the Ospedale San Giovanni in Bellinzona, who presented the study, says that the findings suggest the potential for a new first-line treatment option for patients with asymptomatic or mildly symptomatic bone mCRPC who have not received a prior androgen receptor pathway inhibitor.

The international phase 3 trial included 446 patients with mCRPC and bone metastases randomized 1:1 to ENZ–RAD and ENZ alone. None of the patients had received prior treatment with ENZ or RAD or had known visceral metastases. Prior treatment with abiraterone and docetaxel was permitted for patients with metastatic hormone-sensitive prostate cancer. Most of the patients (87.9%) randomized to the ENZ–RAD arm completed the scheduled six cycles of RAD.

A significant improvement in overall survival also was seen in a preplanned interim analysis, which showed overall survival of 42.3 and 35 months for patients treated with ENZ–RAD and ENZ alone, respectively, with a hazard ratio of 0.69 (95% CI, 0.52–0.90; p = .0031).

More patients treated with ENZ–RAD had treatment-related adverse events in comparison with those treated with ENZ alone. For example, grade 3 or higher events were reported in 65.6% and 55.8% of patients, respectively, with the most frequent events in patients treated with ENZ–RAD being hypertension (34%), fatigue (6%), anemia (5%), and neutropenia (5%).

Walter Stadler, MD, the Fred C. Buffett Professor of Medicine and deputy director of the Comprehensive Cancer Center at the University of Chicago Medicine, says that the findings are potentially practice changing, “assuming that the overall survival is improved with longer follow-up.”

He points out, however, that the findings relate to an increasingly smaller and rarer group of patients who make up the patient population of the study—those with bone mCRPC who have not previously received an androgen receptor signaling inhibitor.

“Most patients receive combined hormonal therapy in the castrate-sensitive state or develop biochemical progression without demonstrable bone metastases while receiving androgen ablation alone,” he says.

He also notes that the value of combining ENZ and RAD in patients who have received prior androgen receptor signaling inhibition therapy is unknown in this study because only 2%–3% of the patients in the study received prior abiraterone treatment.

Dr Stadler underscores that RAD, along with zoledronate or denosumab, remains a valuable treatment option for patients with mCRPC, “but timing of its use and whether to use it in combination with other prostate cancer therapies remain unclear.”