OBJECTIVES: This study evaluated the cost-effectiveness of [¹⁷⁷Lu]Lu‑PSMA‑617 (¹⁷⁷Lu-PSMA-617), a prostate-specific membrane antigen (PSMA) targeted radioligand therapy, against standard of care (SOC) and cabazitaxel for the treatment of progressive PSMA-positive metastatic castration-resistant prostate cancer (mCRPC) in the United Kingdom (UK).

METHODS: A partitioned survival model was developed to capture time spent by patients in progression free, progressed, and dead health states over a lifetime horizon. Parametric survival modelling was used to extrapolate radiographic progression-free survival and overall survival (OS) outcomes from the VISION trial, and real-world evidence to inform OS for cabazitaxel. Network meta-analysis was performed to estimate relative effectiveness for the indirect comparison with cabazitaxel. Symptomatic skeletal event and adverse event incidences were taken from the VISION and CARD trials. EQ-5D data collected in VISION were analyzed to generate health-state utilities. Resource use estimates were informed by the literature and clinical expert opinion, and unit costs were taken from standard UK sources. Comprehensive sensitivity analysis was conducted.

RESULTS: Compared with SOC, ¹⁷⁷Lu-PSMA-617 generated 0.42 incremental quality-adjusted life years (QALYs) and £80,684 incremental costs; the incremental cost-effectiveness ratio (ICER) was £192,514. Compared with cabazitaxel in patients eligible for further chemotherapy, ¹⁷⁷Lu-PSMA-617 generated 0.44 incremental QALYs and £62,368 incremental costs; the ICER was £143,073. The ICERs were most sensitive to alternative approaches to modelling OS and health-state utilities, which directly influence QALY gains. Incremental costs were predominantly attributable to drug acquisition and the ICERs were also sensitive to the price of ¹⁷⁷Lu-PSMA-617.

CONCLUSIONS: 177Lu-PSMA-617 demonstrated substantial incremental QALY gains versus both cabazitaxel and SOC at an incremental cost. The innovative treatment option represents a clinically significant advancement in the management of progressive mCRPC patients with a very poor prognosis.