TOPLINE: 

Patients with metastatic castration-resistant prostate cancer who received Lu-177-PSMA-617 (Pluvicto) achieved similar overall survival and had fewer serious adverse events compared to those who switched androgen receptor pathway inhibitors (ARPI) after progressing on a first-line ARPI. However, the authors noted, the overall survival results "were likely confounded by the high rate of crossover" from a second-line ARPI to Lu-177-PSMA-617.

METHODOLOGY:

• Patients with metastatic castration-resistant prostate cancer who progress on first-line ARPI therapy and are taxane-naive may receive an ARPI in the second-line setting if they are unable to tolerate taxane-based chemotherapy. However, an ARPI is not the most active treatment in this setting.
• In the PSMAfore trial , researchers compared the efficacy of another agent — Lu-177-PSMA-617 — to an ARPI as a second-line treatment option. Overall, 468 patients with PSMA-positive metastatic castration-resistant prostate cancer were randomly assigned to receive either Lu-177-PSMA-617 (n = 234) or ARPI switch (n = 234). Participants had previously experienced disease progression on an ARPI (abiraterone, enzalutamide, darolutamide, or apalutamide) and were deemed appropriate to delay taxane-based chemotherapy.
• Participants received Lu-177-PSMA-617 at a dose of 7.4 GBq once every 6 weeks for six cycles or ARPI change (abiraterone or enzalutamide at the treating physician's discretion). Patients in the ARPI arm could cross over to Lu-177-PSMA-617 after centrally confirmed radiographic progression.