Clinical and economic outcomes of cabazitaxel versus Lu-PSMA in mCRPC: a US perspective

The TheraP trial compared cabazitaxel to Lutetium-177-labeled PSMA-617 (Lu-PSMA) in metastatic castration-resistant prostate cancer (mCRPC) following docetaxel and an androgen receptor pathway inhibitor (ARPI). Lu-PSMA demonstrated improved PSA response (66% vs 37%; p < 0.0001) and progression-free survival (HR = 0.63; p = 0.0028), while overall survival (OS; median 16.4 vs. 19.4 months) and rates of Grade 3 (0.88 vs. 0.96 events/patient) and Grade 4 adverse events (AE; 0.11 vs. 0.08 events/patient) were comparable. The comparative economic implications of these two therapies in the United States (US) remain uncertain.

A cost-consequence Excel model was developed from the US Medicare perspective to evaluate the direct cost outcomes for mCRPC patients receiving cabazitaxel or Lu-PSMA. Inputs were derived from TheraP, supplemented by literature and clinical expert validation. Costs included PSMA testing, drug acquisition and administration, supportive care, AE management, and end-of-life care. Outcomes (derived from TheraP inputs) included OS, progression-free survival (PFS), PSA-PFS, and radiographic-PFS (rPFS). An 18-month time horizon aligned with clinical follow-up. Costs were reported in 2025 USD.

At 18 months in the modeled cohort of 100 patients, cabazitaxel was associated with nine additional modeled survivors; this should be interpreted cautiously, as TheraP reported no statistically significant difference in OS between cabazitaxel and Lu-PSMA. In contrast, Lu-PSMA demonstrated improved PFS outcomes in the modeled cohort, with eight more patients remaining progression-free and 15 more radiographic progression-free. From the Medicare perspective, cabazitaxel was associated with a per-patient cost of $107,729, versus $303,338 per patient for Lu-PSMA (-$195,608). Cost differences were driven primarily by lower drug acquisition costs for cabazitaxel.

Cabazitaxel provides a clinically validated and economically favorable treatment option post-docetaxel and ARPI, providing substantial cost savings across payer scenarios with no observed difference in OS. Lu-PSMA offers improved PSA-based outcomes and progression-related endpoints at higher treatment costs. These findings support clinical-economic trade-off considerations when sequencing therapies for mCRPC.