Top Line: Does Pluvicto improve survival in patients with mCRPC who progress on an androgen receptor pathway inhibitor?
The Study: In the PSMAfore trial, switching to Pluvicto rather than another ARPI in patients with mCRPC who progress on ADT and an ARPI significantly improved the primary endpoint of median radiographic PFS from 5.59 to 11.6 months with less toxicity. Here we have the final overall survival analysis from PSMAfore, which showed no significant difference in median OS with Pluvicto (24.5 months) versus switching to a different ARPI (23.1 months) based on intention to treat. However, 60% of patients in the ARPI arm crossed over to receive Pluvicto including 75% of those who had radiographic progression. Crossover-adjusted OS analysis showed a significant benefit with Pluvicto, which suggests treatment crossover likely had a confounding effect on the OS outcomes. Pluvicto continued to have a lower incidence of grade 3+ toxicity events compared to a change in ARPI.
TBL: Intention to treat analysis of PSMAfore showed no improvement in OS with Pluvicto versus switching ARPIs in those with mCRPC. However, most patients in the ARPI arm crossed over to receive Pluvicto, which likely impacted the final OS results. | Fizazi, Ann Oncol 2025
The Study: In the PSMAfore trial, switching to Pluvicto rather than another ARPI in patients with mCRPC who progress on ADT and an ARPI significantly improved the primary endpoint of median radiographic PFS from 5.59 to 11.6 months with less toxicity. Here we have the final overall survival analysis from PSMAfore, which showed no significant difference in median OS with Pluvicto (24.5 months) versus switching to a different ARPI (23.1 months) based on intention to treat. However, 60% of patients in the ARPI arm crossed over to receive Pluvicto including 75% of those who had radiographic progression. Crossover-adjusted OS analysis showed a significant benefit with Pluvicto, which suggests treatment crossover likely had a confounding effect on the OS outcomes. Pluvicto continued to have a lower incidence of grade 3+ toxicity events compared to a change in ARPI.
TBL: Intention to treat analysis of PSMAfore showed no improvement in OS with Pluvicto versus switching ARPIs in those with mCRPC. However, most patients in the ARPI arm crossed over to receive Pluvicto, which likely impacted the final OS results. | Fizazi, Ann Oncol 2025