In a significant stride forward in treatment options for metastatic castration-resistant prostate cancer (mCRPC), a ground-breaking study has demonstrated the efficacy of combining enzalutamide with lutetium-177 [177Lu]Lu-prostate-specific membrane antigen (PSMA)-617. The findings, published in The Lancet, shed light on the potential of this novel combination therapy in improving overall survival rates among patients with advanced prostate cancer.
The study, dubbed ENZA-p, was a phase 2 clinical trial conducted across 15 hospitals in Australia. It enrolled men aged 18 years and older who had metastatic castration-resistant prostate cancer, Eastern Cooperative Oncology Group performance status of 0–2, and at least two risk factors for early progression on enzalutamide. Importantly, these participants had not previously received treatment with docetaxel or androgen receptor pathway inhibitors for mCRPC.
Researchers randomly assigned 162 participants between August 17, 2020, and July 26, 2022, into two groups: one receiving enzalutamide alone and the other receiving a combination of enzalutamide and adaptive-dosed [177Lu]Lu-PSMA-617. The primary endpoint of the study was prostate-specific antigen (PSA) progression-free survival, a key measure of cancer progression.
Results from the interim analysis revealed promising outcomes. The median follow-up period was 20 months, during which patients receiving the combination therapy exhibited a median PSA progression-free survival of 13.0 months, compared to 7.8 months in those receiving enzalutamide alone. This represents a significant improvement in cancer control, with a hazard ratio of 0.43 favouring the combination therapy group.
Moreover, the safety profile of the combination therapy was found to be manageable. The most common adverse events reported included fatigue, nausea, and dry mouth, with similar rates observed in both groups. Grade 3–5 adverse events occurred in 40% of patients in the combination therapy group and 41% in the enzalutamide-alone group. Notably, no grade 4 or 5 events were attributed to treatment in either group.
These findings suggest that the addition of [177Lu]Lu-PSMA-617 to enzalutamide not only improves PSA progression-free survival but also demonstrates enhanced anticancer activity in patients with mCRPC. The results underscore the need for further evaluation of this combination therapy in the broader context of metastatic prostate cancer treatment.
The study, registered with ClinicalTrials.gov under the identifier NCT04419402, marks a significant milestone in the ongoing efforts to enhance treatment options and outcomes for individuals battling advanced prostate cancer. As researchers continue to explore novel therapeutic approaches, the hope is that such advancements will translate into improved survival rates and quality of life for patients worldwide.
Paper: Emmett, L,. et al. [177Lu]Lu-PSMA-617 plus enzalutamide in patients with metastatic castration-resistant prostate cancer (ENZA-p): an open-label, multicentre, randomised, phase 2 trial. The Lancet. April 12, 2024. DOI:https://doi.org/10.1016/S1470-2045(24)00135-9
