As reported in The Lancet by Morris et al, the phase III PSMAfore trial has shown improved progression-free survival with lutetium-177–labeled PSMA-617 (LuPSMA) vs change in androgen receptor pathway inhibitor (ARPI) in taxane-naive patients with metastatic castration-resistant prostate cancer whose disease progressed on an ARPI.
Study Details
KEY POINTS
- LuPSMA improved radiographic progression-free survival vs change in ARPI.
- Median radiographic progression–free survival on primary analysis was 9.30 vs 5.55 months.
In the open-label trial, 468 patients from sites in Europe and North America were randomly assigned between June 2021 and October 2022 to receive LuPSMA at 7.4 GBq (200 mCi) ± 10% every 6 weeks for six cycles (n = 234) or ARPI change (n = 234) to abiraterone (n = 100) or enzalutamide (n = 132) given continuously per product labeling. The primary endpoint was radiographic progression–free survival on blinded independent central review in the intention-to-treat population. Primary analysis was performed at first data cutoff, and updated analysis was performed at third data cutoff.
Progression-Free Survival
In the primary analysis, with median follow-up of 7.26 months (interquartile range [IQR] = 3.38–10.55 months), median radiographic progression–free survival was 9.30 months (95% confidence interval [CI] = 6.77 months to not estimable) in the LuPSMA group vs 5.55 months (95% CI = 4.04–5.95 months) in the ARPI-change group (hazard ratio [HR] = 0.41, 95% CI = 0.29–0.56, P < .0001).
At updated analysis, with median follow-up of 24.11 months (IQR = 20.24–27.40 months), median radiographic progression–free survival was 11.60 months (95% CI = 9.30–14.19 months) in the LuPSMA group vs 5.59 months (95% CI =4.21–5.95 months) in the ARPI-change group (HR = 0.49, 95% CI = 0.39–0.61).
Adverse Events
Among the 237 patients in the LuPSMA group and 232 in the ARPI group who received at least one dose of study medication, grade ≥ 3 adverse events occurred in 36% vs 48% of patients; the most common in both groups was anemia (6% vs 7%). Adverse events led to discontinuation of treatment in 6% vs 5% of patients. Adverse events led to death in 2% of patients in each group; treatment-related death occurred in one patient in the ARPI-change group, due to cerebrovascular accident.
The investigators concluded: “[LuPSMA] prolonged radiographic progression–free survival relative to ARPI change, with a favourable safety profile. For patients with PSMA-positive metastatic castration-resistant prostate cancer who are being considered for a change of ARPI after progression on a previous ARPI, [LuPSMA] may be an effective treatment alternative.”
Michael J. Morris, MD, of Memorial Sloan Kettering Cancer Center, is the corresponding author for The Lancet article.
Disclosure: The study was funded by Novartis. For full disclosures of the study authors, visit www.thelancet.com.
