KEY TAKEAWAYS
- The PSMAfore phase III trial aimed to assess the efficacy and safety of [177Lu]Lu-PSMA-617 in taxane-naive mCRPC pts.
- The primary endpoint was rPFS. The key secondary endpoint was OS.
- The study found 177Lu-PSMA-617 extended rPFS, demonstrating a favorable safety profile in taxane-naive mCRPC pts.
In a study, [177Lu]Lu-PSMA-617 (177Lu-PSMA-617) has previously shown promise in extending radiographic progression-free survival (rPFS) and overall survival (OS) in metastatic castration-resistant prostate cancer (mCRPC) patients(pts)who have received prior androgen receptor pathway inhibitor (ARPI) and taxane therapy.
Eligible adults with mCRPC, candidates for ARPI change after one progression on prior ARPI, and having ≥1 PSMA+ with no exclusionary PSMA– lesions by [68Ga]Ga-PSMA-11 PET/CT were enrolled. Exclusions included candidates for PARP inhibition and those with recent systemic radiotherapy (<6 months ago), immunotherapy (except sipuleucel-T), or chemotherapy (except [neo]adjuvant >12 months ago).
Randomization was 1:1 to open-label 177Lu-PSMA-617 (7.4 GBq q6w; 6 cycles) or ARPI change (abiraterone/enzalutamide). Pts randomized to ARPI could crossover to 177Lu-PSMA-617 upon centrally reviewed radiographic progression (rPD). Endpoints included rPFS (PCWG3/RECIST v1.1; primary), OS (key secondary) (both overall α=0.025, one-sided), FACT-P (secondary), and ORR/DOR (exploratory).
The primary analysis was planned at ∼156 rPFS events, with a second OS interim analysis (IA) at ∼125 deaths. Crossover-adjusted analysis was the prespecified method for OS using rank-preserving structural failure time (RPSFT).
In the randomized trial involving 68 pts, the primary analysis (median follow-up, 7.3 months; N = 467) demonstrated that the primary endpoint of rPFS was achieved (HR, 0.41; 95% CI: 0.29, 0.56; P<0.0001). This outcome remained consistent in the second interim analysis (IA) (45.1% of target deaths).
At the second IA, 84.2% of pts with radiographic progression who discontinued ARPI crossed over to 177Lu-PSMA-617. While there was a positive OS trend favoring 177Lu-PSMA-617 per rank-preserving structural failure time (RPFST), unadjusted OS analysis did not show the same trend. FACT-P and ORR/DOR favored the 177Lu-PSMA-617 arm.
In the comparison of 177Lu-PSMA-617 vs ARPI change, the incidence of grade ≥3 adverse events(AEs) was 34% (most common: anemia, dry mouth) vs 44%, serious AEs were 20% vs 28%, and AEs leading to discontinuation were 5.7% vs 5.2%.
The study found 177Lu-PSMA-617 extended rPFS, demonstrating a favorable safety profile in taxane-naive mCRPC pts.
Clinical Trial: https://clinicaltrials.gov/study/NCT04689828
Sartor O, Castellano Gauna DE, Herrmann K, de Bono JS, Shore ND, Chi KNN, Crosby M, Piulats JM, Flechon A, Wei XX, Mahammedi H, Roubaud G, Studentova H, Ghebremariam S, Kpamegan E, Kreisl TN, Delgoshaie N, Lehnhoff K, Morris MJ, Fizazi K. Phase III trial of [177Lu]Lu-PSMA-617 in taxane-naive patients with metastatic castration-resistant prostate cancer (PSMAfore). Presented by Oliver Sartor, MD, at ESMO 2023. LBA13.
