Outcomes of cabazitaxel following 177Lu-PSMA-617 (LuPSMA) in patients with metastatic castration-resistant prostate cancer (mCRPC).

Abstract

84 Background: LuPSMA and cabazitaxel are both standard of care options for men with PSMA-positive mCRPC post docetaxel. The phase 2 TheraP study demonstrated comparable overall survival (OS), although LuPSMA was associated with a more favorable toxicity profile and higher ≥50% PSA decline (PSA 50 ) rates. Consequently, LuPSMA is often preferred when available. Therefore, we retrospectively evaluated men who received cabazitaxel after LuPSMA to better define prognosis and inform treatment sequencing for this high-risk population. Methods: We identified consecutive men with mCRPC previously treated with ARPI and docetaxel who received ≥1 cycle of LuPSMA followed by cabazitaxel. Secondary endpoints included PSA progression-free survival (PSA-PFS) and OS, measured from the first cycle of cabazitaxel, and hematologic toxicity. Efficacy endpoints were stratified by PSA 50 response to LuPSMA and compared using log-rank test. PSA progression followed PCWG3 criteria. Results: Of 237 patients treated with LuPSMA (June 2022–January 2025), 28 (11.8%) subsequently received cabazitaxel. Among these 28 patients, 23 (82.1%) received ≥2 lines of ARPI therapy, and 1 (3.6%) received PARP inhibitor. Median age was 72.5 (range 65–88); median LuPSMA and cabazitaxel cycles were 3.5 (1–6) and 4 (1–11), respectively. PSA 50 was achieved in 35.7%. Median PSA-PFS was 2.1 months (95% CI 1.6–5.3) and OS 5.5 months (3.0–13.4). Nine patients (32%) achieved PSA 50 with LuPSMA; of these, 5 (56%) again achieved PSA 50 with cabazitaxel. Median PSA-PFS was 1.8 months (1.5–4.8) in LuPSMA non-responders vs 6.4 (1.3–NR) in responders (p = 0.11). OS was 5.0 months (3.8–14.1) vs 11.8 (4.0–NR) in non-responders vs responders (p = 0.07). Grade ≥3 thrombocytopenia and neutropenia occurred in 9 and 4 patients, respectively. Conclusions: Cabazitaxel demonstrates modest activity following LuPSMA. While PSA 50 were comparable to historical data, the poor survival outcomes suggest reduced taxane sensitivity. Patients who responded to LuPSMA trended to also have better responses with cabazitaxel. Prospective studies are warranted to define optimal sequencing and patient selection criteria.