CRPC: Evidence
International, open-label, phase III trial
Population
- Patients with mCRPC treated with:
- ≥1 ARPI and
- 1-2 taxane regimens
- Protocol-permitted SOC planned before randomisation
- Excluding chemotx, immunotx, Ra-223, investigational drugs
- ECOG PS 0-2
- Life expectancy >6 mo
- PSMA-positive mCRPC on PET/CT with 68Ga-PSMA-11
Design
- Stratification factors: ECOG PS, LDH, liver mets, ARPI in SOC
- CT/MRI/bone scans: at baseline, every 8 wk for 24 wk after starting tx, every 12 wk until end of tx and every 12 wk during FU (BICR)
Endpoints
Alternate primary endpoints: rPFS (PWG3) and OS (study positive if ≥1 is significant)
Secondary endpoints:
- Time to 1st SSE
- ORR (RECIST v1.1)
- DCR (RECIST v1.1)
- Safety & tolerability
- Biomarkers
- HRQoL and pain
In the SOC alone arm, approximately 60% received steroids and approximately 60% received ARPI switch
Primary endpoints significantly favoured 177Lu-PSMA-617
Other key secondary endpoints favoured 177Lu-PSMA-617
| Median time to... (mo) | Lu-PSMA + SOC (N=385) | SOC alone (N=196) | HR (95% CI) |
|---|---|---|---|
| Worsening pain | 5.9 | 2.2 | 0.52 (0.43-0.63) |
| Worsening HRQoL | 5.7 | 2.2 | 0.54 (0.45-0.66) |
| First symptomatic skeletal event | 11.5 | 6.8 | 0.50 (0.40-0.62) |
- Grade ≥3 AEs occurred in 53% of patients in the experimental arm vs 38% of patients in the control arm
- The most common AEs in the experimental arm were fatigue (43%), dry mouth (39%), nausea (35%) and anaemia (32%)
- The incidence of any grade tx-emergent AEs was similar in cycles 1-4 and cycles 5-6
- The trial has been criticised for having a weak control arm (2)
Key messages:
- 177Lu-PSMA-617 prolonged imaging-based PFS and OS when added to SOC
- The trial has been criticised for having a weak control arm (~60% received ARPI switch)
1. Sartor O, de Bono J, Chi KN, et al. N Engl J Med 2021;385:1091-103; 2. Van Wambeke S, Vera-Badillo FE, Gyawali B, J Clin Oncol 2022;40:1518-21