(UroToday.com) In the on-demand poster session of the European Society for Medical Oncology (ESMO) Annual Congress, Dr. Scott Tagawa presented a trial in poster summary of the PSMAddition trial. This trial was launched given the proven benefits of [177Lu]Lu-PSMA-617 (177Lu-PSMA-617). 177Lu-PSMA-617 is a high-affinity prostate-specific membrane antigen (PSMA)-targeted radioligand therapy that delivers β-particle radiation to cells that express PSMA, as well as the surrounding microenvironment. While 177Lu-PSMA-617 has recently shown benefit in metastatic castration resistant prostate cancer, other treatment approaches including androgen receptor pathway inhibitors (ARPI) have been utilized in this disease space and metastatic hormone-sensitive prostate cancer (mHSPC) for many years. Notably, ARPI treatment may alter PSMA expression and radiosensitivity. Thus, the PSMAddition trial is designed to assess the efficacy and safety of 177Lu-PSMA-617 plus standard of care (SOC) versus SOC alone in adults with metastatic hormone-sensitive prostate cancer (mHSPC).
PSMAddition (NCT04720157) is an international prospective open-label, randomized, phase III trial in adult men with mHSPC. To be eligible, patients must be treatment-naïve or minimally treated candidates for hormonal therapy. Further, they must have evidence of PSMA-positive disease (determined by [68Ga]Ga-PSMA-11 PET/CT) as well as ECOG performance status of 0 to 2 and adequate major organ function. Notably, patients are excluded if they have rapidly progressing tumours that require chemotherapy.
The authors plan to accrue approximately 1126 patients. Once enrolled, patients will be randomized 1:1 to receive 177Lu-PSMA-617 (7.4 GBq i.v. every 6 weeks, ≤ 6 cycles) plus SOC or SOC alone (control arm). In the context of this trial, the SOC is ARPI and androgen deprivation therapy. Randomization will be stratified according to tumour volume (high/low), age (≥ 70/< 70 years) and previous/planned prostatectomy or radiation treatment of the primary prostate tumour (yes/no).
The primary endpoint of the PSMAddition trial is radiographic progression-free survival (rPFS), as assessed by blinded independent centralized review. Following centrally confirmed radiographic progression, cross-over is allowed for participants in the control arm to the 177Lu-PSMA-617 arm. The planned sample size of 1126 randomized patients provides 95% power to detect a hazard ratio of 0.7 for rPFS after 418 events with an overall one-sided significance level of 0.025. The key secondary endpoint is overall survival and other secondary endpoints include the proportion of patients with a prostate-specific antigen (PSA) decline of ≥ 90% from baseline, time to development of metastatic castration resistant prostate cancer, composite progression-free survival (radiographic, clinical, or PSA progression), safety and tolerability, and health-related quality of life.