LuPSMA Versus Cabazitaxel for mCRPC

By Emily Menendez - Last Updated: November 14, 2022

A report published in The Lancet Oncology showed that an analysis of the phase 2 TheraP trial found higher gallium-68–labeled PSMA-11-positron emission tomography (PET) mean standardized uptake values (SUVmean) were associated with a greater likelihood of prostate-specific antigen (PSA) response to lutetium-177–labeled PSMA-617 (LuPSMA) against cabazitaxel in patients with metastatic castration-resistant prostate cancer. Previous reports from the study had shown that LuPSMA improved PSA response rate and progression-free survival compared with cabazitaxel.

The phase 2 TheraP trial included 200 patients randomly assigned to receive LuPSMA 6.0 to 8.5 GBq intravenously every 6 weeks for up to 6 cycles (n=99) or cabazitaxel at 20 mg/m² every 3 weeks for up to 10 cycles. Out of 35 patients in the LuPSMA group and 30 patients in the cabazitaxel group with an SUVmean ≥10 on PSMA PET, PSA response was seen in 32 versus 14 patients. In 64 and 71 patients with an SUVmean <10, response was seen in 33 versus 23 patients.

High-volume disease was seen in 30 patients in both the LuPSMA and cabazitaxel groups, with 69 LuPSMA patients and 71 cabazitaxel patients having a metabolic tumor volume <200 mL. PSA response was seen in 23 of 60 patients in both groups combined, with a metabolic tumor volume ≥200 mL. Response was also seen in 79 of 140 patients with a metabolic tumor volume <200 mL.

The study investigators concluded that “PSMA-PET SUVmean was predictive of higher likelihood of favorable response to LuPSMA than cabazitaxel, which provides guidance for optimal LuPSMA use. High [fluorodeoxyglucose]-PET was associated with lower responses regardless of randomly assigned treatment, warranting further research for treatment intensification. A strength of this analysis is the validation of prespecified cut points within a multicenter, randomized controlled trial. Quantitative PET parameters used, however, require specialized software and are not yet routinely available in most clinics.”



Biomarker Assessment for Benefit of LuPSMA vs Cabazitaxel in Metastatic Castration-Resistant Prostate Cancer