177Lu-PSMA-617 leads to a better quality of life and a better pain control than a change in androgen receptor pathway inhibitor in patients with metastatic castration-resistant prostate cancer

Previously, the phase III PSMAfore study demonstrated a significantly better radiographic progression-free survival (rPFS) with ¹⁷⁷Lu-PSMA-617 compared to a change in androgen receptor pathway inhibitor (ARPI) in patients with ARPI-pretreated metastatic castration-resistant prostate cancer (mCRPC). Additional results of this study, presented at ASCO 2024, show that ¹⁷⁷Lu-PSMA-617 also leads to a significantly better quality of life and pain control.

Background

In the randomised, phase III PSMAfore trial, 468 taxane-naïve patients with mCRPC who were candidates for a change in androgen receptor pathway inhibitor (ARPI) and had ≥1 PSMA-positive and no exclusionary PSMA-negative metastatic lesions by ⁶⁸Ga-PSMA-11 PET/CT were randomly assigned to receive ¹⁷⁷Lu-PSMA-617 (7.4 GBq/6 weeks; 6 cycles) or a change in ARPI (abiraterone or enzalutamide). Previous results of this study showed that ¹⁷⁷Lu-PSMA-617 was associated with a significantly longer radiographic progression-free survival (rPFS) than an ARPI change.

Secondary endpoints of the PSMAfore study included time to worsening (TTW) in self-reported health-related quality of life (HRQoL; FACT-P, EQ-5D-5L) and pain (BPI-SF), defined as a composite of score worsening (prespecified thresholds), clinical progression (including new anti-cancer treatment) or death. 

Results

The median duration of treatment exposure in the study was 8.4 months for ¹⁷⁷Lu-PSMA-617 and 6.5 months for ARPI change. ¹⁷⁷Lu-PSMA-617 significantly delayed the TTW in FACT-P (HR[95%CI]: 0.59[0.47-0.72]) and EQ-5D-5L (HR[95%CI]: 0.61[0.50-0.76]) compared to ARPI change. In addition to this, also the TTW of the FACT-P subscales were improved with ¹⁷⁷Lu-PSMA-617 relative to an ARPI change in terms of physical well-being (HR[95%CI]: 0.55[0.45-0.68]), emotional well-being (HR[95%CI]: 0.66[0.53-0.82]), and functional well-being (HR[95%CI]: 0.77[0.63-0.95]). However, this was not the case for social/family well-being (HR[95%CI]: 0.85[0.69-1.06]).

The BPI-SF scales of TTW pain intensity (HR[95%CI]: 0.69[0.56-0.85]), TTW pain interference (HR[95%CI]: 0.67[0.54-0.83]), and time to disease-related pain (HR[95%CI]: 0.70[0.57-0.85]) were also improved with ¹⁷⁷Lu-PSMA-617 compared to a change in ARPI. Also when patients that had clinical progression or death were excluded, the FACT-P total score (HR[95%CI]: 0.48[0.37-0.63]) and BPI-SF pain intensity (HR[95%CI]: 0.64[0.50-0.83]) remained statistically better for patients receiving ¹⁷⁷Lu-PSMA-617 vs. ARPI change.

Conclusions

In the phase III PSMAfore study, ¹⁷⁷Lu-PSMA-617 statistically outperformed an ARPI change in terms of rPFS, HRQoL and pain control. Together, these data support ¹⁷⁷Lu-PSMA-617 as a treatment option for patients with mCRPC who progressed under an ARPI.

Reference

Fizazi K, et al. Health-related quality of life and pain in a phase 3 study of [177Lu]Lu-PSMA-617 in taxane-naïve patients with metastatic castration-resistant prostate cancer (PSMAfore). Presented at ASCO 2024; Abstract 5003.