In PSMAddition (NCT04720157), combining 177Lu-PSMA-617 with ADT + ARPI significantly improved rPFS, vs ADT + ARPI, in patients with PSMA+ mHSPC (HR 0.72; 95% CI 0.58, 0.90; p = 0.002) at interim analysis 2 (IA2). We present health-related quality of life (HRQoL), pain and symptomatic skeletal events (SSE) results at rPFS IA2 (data cutoff, Jan 13, 2025).
Eligible patients had treatment-naive/minimally treated (≤45 days pre-consent) mHSPC and ≥1 PSMA+ metastatic lesion on [ 68Ga]Ga-PSMA-11 PET/CT. Patients were randomized 1:1 to 177LuPSMA-617 (7.4 GBq ± 10% q6w, 6 cycles) + ADT + ARPI ( 177Lu-PSMA-617 arm) or to ADT + ARPI alone (control arm). The primary endpoint was rPFS (BIRC-confirmed rPD by PCWG3/RECIST v1.1 or death). Safety and tolerability were secondary endpoints. Secondary endpoints also included time to worsening (TTW) in patient-reported HRQoL (FACT-P, EQ-5D-5L) and pain (BPISF), defined as composites of score worsening by prespecified thresholds, clinical progression, or death; and composite time to SSE (TTSSE) or death. Post hoc non-composite analyses excluded death and clinical progression.
1144 patients were randomized. Median study treatment exposure was 20.6 months in the 177LuPSMA-617 arm and 19.94 months in the control arm. Overall incidences of grade ≥3 AEs and serious AEs were 50.7% and 26.6%, respectively, in the 177Lu-PSMA-617 arm and 43.0% and 22.8% in the control arm. HRs for TTW in all FACT-P, EQ-5D-5L, and BPI-SF scales/subscales were >1.0 but <1.2, and all 95% CIs included 1.0 (Table) ( 177Lu-PSMA-617 arm vs control arm). Post hoc results were similar. The HR for TTSSE was 0.89 (95% CI 0.62, 1.26); medians were not reached. Post hoc results were similar.
Combining 177Lu-PSMA-617 with ADT + ARPI improved rPFS, with a trend toward prolonged TTSSE, vs ADT + ARPI, in patients with PSMA+ mHSPC. The frequency of AEs was slightly increased, but there were no clinically significant differences in TTW in HRQoL and pain.