Selecting Patients for ¹⁷⁷Lu-PSMA-617

Theranostics · 2 min read

VISION, TheraP and the label each define PSMA-positive differently

Every ¹⁷⁷Lu-PSMA-617 decision starts with a PSMA PET. The two trials that proved the drug used different PET rules, and the labels define none. Knowing both rule sets tells you what to look for and what to write.

VISION: liver as the threshold

• Centrally read ⁶⁸Ga-PSMA-11 PET plus diagnostic CT.
• PSMA-positive: at least one metastasis with uptake greater than liver parenchyma.
• Exclusion: any PSMA-negative lesion (uptake equal to or below liver) above size limits: lymph node short axis ≥2.5 cm, solid-organ lesion ≥1.0 cm, or bone lesion with a soft-tissue component ≥1.0 cm.
• Of 1003 men scanned, 126 (12.6%) failed these criteria.
• Result: median overall survival 15.3 vs 11.3 months (hazard ratio 0.62); imaging-based progression-free survival 8.7 vs 3.4 months.

TheraP: SUV thresholds and FDG

• ⁶⁸Ga-PSMA-11 and FDG PET for every patient.
• Inclusion: SUVmax ≥20 at one site of disease and SUVmax >10 at all measurable sites ≥10 mm.
• Exclusion: any FDG-positive site with minimal PSMA expression (FDG more intense than PSMA, or PSMA SUVmax <10).
• Of 291 men screened, 200 were eligible on PET. PSA fell by at least 50% in 66% on ¹⁷⁷Lu-PSMA-617 and 37% on cabazitaxel.

What intensity and discordance add

• In TheraP, men with whole-body PSMA SUVmean ≥10 had a 91% PSA response to ¹⁷⁷Lu-PSMA-617, against 52% below that cut-off.
• In VISION, each one-unit rise in whole-body SUVmean lowered the risk of death by 10%. Median survival was still longer with treatment in every SUVmean quartile, though not significantly in the lowest. Low uptake predicts less benefit, not necessarily none.
• Men excluded from an earlier phase 2 trial for low PSMA or FDG-discordant disease had a median survival of 2.5 months.
• EANM/SNMMI: FDG PET is not mandatory for all, but helps when lesion viability or PSMA negativity is uncertain, especially in liver metastases.

What the label says

The US label: select patients with an approved PSMA PET agent “based on PSMA expression in tumors”; the trial criteria sit in the clinical studies section. The EU label: patients “should be identified for treatment by PSMA imaging”. Neither gives a threshold. Indications also differ: the EU label covers progressive mCRPC after an androgen-receptor pathway inhibitor and a taxane; the current US label extends to taxane-naive and earlier settings.