Activity of Lutetium-177 Prostate-Specific Membrane Antigen and Determinants of Outcomes in Patients with Metastatic Castration-Resistant Prostate Cancer Previously Treated with Cabazitaxel: The PACAP Study - Beyond the Abstract
With the widespread approval of Lu-PSMA, optimal selection of patients has been a key consideration for physicians facing a variety of clinical settings. Most patients treated with Lu-PSMA in the VISION trial were not previously treated with cabazitaxel, another life-prolonging agent after docetaxel and NHA, and only limited data was available for Lu-PSMA activity in this context. The life expectancy > 6 months required for the inclusion of patients within the VISION trial may have also prompted the inclusion of patients with indolent disease courses, which may not accurately reflect the real-life use of Lu-PSMA.
We conducted the European multicenter PACAP study to evaluate the real-life activity of Lu-PSMA after cabazitaxel, understand the determinants of response, and ultimately help improve patient selection. We found a compelling rate of objective radiological response (35%) and PSA decline (44%), but activity was short-lived in this unselected population: radiological progression-free survival was only 4 months, and the time to PSA progression was 3.5 months. Among factors associated with adverse outcomes, short time to castration resistance and high ISUP grade was associated with lesser activity of Lu-PSMA, as well as FDG uptake in patients who had FDG-PET at baseline. Conversely, high PSMA uptake (SUVmean and SUVmax) was associated with better outcomes on Lu-PSMA, as well as depth of PSA decline on therapy.
This work highlights the importance of patient selection based on disease characteristics and PET parameters, as well as thorough follow-up of PSA on-therapy. It also supports widespread integration of both FDG and PSMA-PET in routine practice, which could be further implemented into clinical trials though efforts towards standardized criteria are still underway. Real-world evaluation of Lu-PSMA in earlier settings will be important to improve treatment sequencing with a wider range of therapeutic options available.
Written by: Ronan Flippot, MD, MSc, Medical Oncologist, Department of Cancer Medicine, Gustave Roussy, Paris Saclay University, Villejuif, France
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