Meta-analysis shows PFS benefit with 177Lu-PSMA-617 in mCRPC

In a recent meta-analysis presented at the 2026 Multidisciplinary Radiopharmaceutical Therapy Symposium in Palm Desert, California, ¹⁷⁷Lu-PSMA-617 demonstrated an improvement in progression-free survival (PFS) compared with standard therapies for metastatic castration-resistant prostate cancer (mCRPC).¹

The results were presented by Mohammad Arfat Ganiyani, MBBS, a postdoctoral research fellow at the Miami Cancer Institute in South Florida.

“¹⁷⁷Lu-PSMA-617 delivers β radiation to the PSMA-expressing tumor cells. This is mechanistically different from the other systemic therapies that we used in patients [with mCRPC], like androgen receptor pathway inhibitors and chemotherapy,” Ganiyani explained during the presentation. “There have been several trials like VISION and ENZA-p, where they have shown [an] overall survival [OS] benefit in mCRPC setting. However, other trials have just shown PFS benefit. Therefore, we designed this study to evaluate efficacy and toxicity of lutetium across all the [phase 2/3] randomized controlled trials.”

For the analysis, the investigators conducted a systematic review of the literature and included randomized phase 2/3 clinical trials that enrolled patients with mCRPC and assigned them to receive ¹⁷⁷Lu-PSMA-617 vs standard therapies. The trials needed to report PFS, OS, and the rates of grade 3 or higher adverse events (AEs). A total of 7 studies met these criteria and were included for analysis. These studies included ENZA-p (NCT04419402), PSMAfore (NCT04689828), Satapathy et al, TheraP (NCT03392428), VISION (NCT03511664), CCT Group PR.21 (NCT04663997), and SPLASH (NCT04647526).

Overall, the analysis included data from 2526 patients across all 7 studies, of whom 1365 received ¹⁷⁷Lu-PSMA-617 and 1161 received standard therapies. The pooled median age was 71.2 years, with a median age of 70.8 years in the ¹⁷⁷Lu-PSMA-617 arm and 71.8 years in the standard therapies arm.

In the pooled analysis, ¹⁷⁷Lu-PSMA-617 demonstrated a significant benefit in PFS compared with standard therapies (HR, 0.64; 95% CI, 0.50-0.81; P < .001). However, there was no significant difference in OS between the 2 treatment arms (HR, 0.91; 95% CI, 0.66-1.25; P = .55).

According to the authors, the OS finding “likely reflect[s] postprogression and salvage use of Lu-177 PSMA-617 in control arms in some trials, as well as disease and trial heterogeneity.”

The data also showed no statistically significant difference in the risk of overall grade 3 or higher AEs between the 2 groups (RR, 0.98; 95% CI, 0.83-1.14; P = .75). When looking at specific AEs, the relative risk of thrombocytopenia was found to be statistically significant (pooled RR, 5.79; 95% CI, 2.14-15.65; P = .0005; Cochran Q test = 0.72).

There was no significant small-study effects/publication bias detected in any of the outcomes, as assessed using Egger regression and Begg rank-correlation tests.

Based on these findings, the authors concluded, “The data collectively reinforce Lu-177 PSMA-617 as a well-tolerated, effective radioligand option for advanced mCRPC, warranting continued integration into earlier disease settings and combination strategies.”

REFERENCE

1. Ganiyani MA, Sheraz A, Syed DH, et al. Safety and efficacy of Lu-177 PSMA-617 versus established therapies in mCRPC: pooled evidence from randomized phase II/III trials. Presented at: 2026 Multidisciplinary Radiopharmaceutical Therapy Symposium; February 17-18, 2026; Palm Desert, CA.