Comparison of two alternative sequences with cabazitaxel and 177Lu-P-SMA-617 in metastatic castration-resistant prostate cancer: A retrospective multicenter study (LuCaS)

Background: Cabazitaxel and 177Lu-PSMA-617 have been shown to improve survival in patients with metastatic castration-resistant prostate cancer (mCRPC) previously treated with docetaxel and androgen receptor pathway inhibitors (ARPI). we aimed to evaluate the impact of sequencing cabazitaxel and 177Lu-PSMA-617 on survival outcomes in patients with mCRPC. Patients and methods: This is a retrospective, multicenter, cohort study which included patients with mCRPC who received sequential treatment with 177Lu-PSMA-617 and cabazitaxel between January 2015 and December 2023. Primary outcome was progression-free survival-2 (PFS-2) Results: A total of 68 patients with mCRPC who received sequential 177Lu-PSMA-617 and cabazitaxel were included in the study. The primary outcome, progression-free survival-2 (PFS-2), was similar in patients treated with 177Lu-PSMA-617 first (LU-CA) and those receiving cabazitaxel (CA-LU) first (10.8 and 11.7 months, respectively; p = 0.422). The median overall survival (OS) was also similar in the LU-CA and CA-LU groups (16.6 and 19.9 months, respectively; p = 0.917). The objective response rate (ORR) for 177Lu-PSMA-617 was 23.1 % when used first and 16.1 % after cabazitaxel. ORR for cabazitaxel was 25.6 % and 31.3 % when used as the first agent and when used after 177Lu-PSMA-617, respectively. Conclusions: In conclusion, treatment sequencing between cabazitaxel and 177Lu-PSMA-617 did not significantly affect survival outcomes in patients with mCRPC. These findings suggest that both drugs can be effectively integrated into the mCRPC treatment paradigm without concerns about the effect of sequencing. However, prospective data are needed to optimize sequencing strategies and explore their impact on specific patient subgroups for more personalized care.