In an analysis of an Australian phase II trial (ENZA-p) reported in The Lancet Oncology, Emmett et al reported that the addition of lutetium-177–labeled PSMA-617 (LuPSMA) to enzalutamide improved overall survival and several aspects of health-related quality of life (HRQOL) in the first-line treatment of patients with castration-resistant metastatic prostate cancer.
Interim analysis of the trial showed that the combination improved prostate-specific antigen progression-free survival. The current report features the secondary endpoints of overall survival and HRQOL with additional follow-up.
Study Details
In the multicenter, open-label trial, 79 patients were randomly assigned between August 2020 and July 2022 to receive enzalutamide plus LuPSMA (n = 83) or enzalutamide alone (n = 79). Patients had received no prior docetaxel or androgen receptor pathway inhibitors for metastatic disease and had at least two risk factors for early progression on enzalutamide. Treatment consisted of enzalutamide at 160 mg daily alone or with adaptive-dosed (two or four doses) LuPSMA at 7.5 GBq every 6 to 8 weeks. HRQOL was assessed with the EORTC QLQ-C30 and the Patient Disease and Treatment Assessment Form.
Key Findings
Median follow-up was 34 months (interquartile range = 29–39 months). Death occurred in 52% of the combination group and 67% of the control group.
Median overall survival was 34 months (95% confidence interval [CI] = 30–37 months) in the combination group vs 26 months (95% CI = 23–31 months) in the control group (HR = 0.55, 95% CI = 0.36–0.84, P = .0053).
For HRQOL, deterioration-free survival at 12 months favored the combination group for both physical function (median = 10.64 months vs 3.42 months, HR = 0.51, P < .0001) and for overall health/QOL (median = 8.71 months vs 3.32 months, HR = 0.47, P = .0001). Mean scores for pain until progression favored the combination group (difference = 7.3, P = .012). Mean scores for fatigue until progression favored the combination group (difference = 5.9, P = .016). The frequency of xerostomia was lower in the control group (57% vs 74%, P = .039), with scores not significantly differing between groups for all other domains.
No treatment-related deaths were reported.
Conclusion
The investigators concluded: “The addition of [LuPSMA] to enzalutamide was associated with improved survival and some aspects of HRQOL in patients with high-risk metastatic castration-resistant prostate cancer. Our findings warrant phase III evaluation of adaptive-dosed [LuPSMA] in combination with androgen receptor pathway inhibitors in people with metastatic prostate cancer.”
Louise Emmett, MD, Department of Theranostics and Nuclear Medicine, St. Vincent’s Hospital, Sydney, is the corresponding author for The Lancet Oncology article.
Disclosures: The study was funded by the Prostate Cancer Research Alliance initiative (Movember and Australian Federal Government), St. Vincent’s Clinic Foundation, AdAcAp (a Novartis company), Astellas, and others. For full disclosures of all study authors, visit www.thelancet.com.
