Real-World Comparison of Cabazitaxel Versus ¹⁷⁷Lu-PSMA Radiopharmaceutical Therapy in Metastatic Castration-Resistant Prostate Cancer

¹⁷⁷Lu-vipivotide tetraxetan prostate-specific membrane antigen (¹⁷⁷Lu-PSMA) therapy is under current scientific investigation and aims to become established in the treatment of metastatic castration-resistant prostate cancer (mCRPC). However, real-world evidence in treatment comparison is scant. Methods: We relied on the FRAMCAP database and compared cabazitaxel versus ¹⁷⁷Lu-PSMA therapy in mCRPC patients regarding progression-free survival (PFS) and overall survival (OS). Sensitivity analyses addressed second- to fourth-line mCRPC treatment to approximate current phase III patient selection criteria. Results: Of 373 patients, 14% received cabazitaxel, 65% received ¹⁷⁷Lu-PSMA, and 21% received both. Patients undergoing ¹⁷⁷Lu-PSMA therapy were significantly older than cabazitaxel patients (median, 72 y vs. 66 y; P < 0.01), and a higher proportion had an Eastern Cooperative Oncology Group score of 2 or more (12% vs. 5.0%, P = 0.1). Rates of a prostate-specific antigen decline of at least 50% were 32% versus 0% for ¹⁷⁷Lu-PSMA versus cabazitaxel. In outcome analyses, significant superior median PFS was observed for ¹⁷⁷Lu-PSMA versus cabazitaxel (13.4 mo vs. 7.1 mo, P < 0.001), even after multivariable adjustment (hazard ratio, 0.38; P < 0.001). Regarding OS, rates also significantly differed, with median OS of 14.7 mo versus 16.5 mo versus 29.6 mo for cabazitaxel versus ¹⁷⁷Lu-PSMA versus both treatments (P < 0.01). In sensitivity analyses of second- to fourth-line mCRPC treatment, PFS rates and median OS rates for cabazitaxel versus ¹⁷⁷Lu-PSMA versus both therapies qualitatively remained the same as for the entire cohort. Conclusion: In a real-world setting, ¹⁷⁷Lu-PSMA provides significantly better PFS and qualitatively better OS rates than does cabazitaxel chemotherapy and should therefore be considered a valuable treatment option for advanced mCRPC patients according to the European Medicines Agency approval.