Top Line: Is 177Lu-PSMA-617 an effective first-line treatment for metastatic castration resistant prostate cancer?
The Study: ENZA-p was a randomized, phase 2 trial from Australia that sought to determine if adding 177Lu-PSMA-617 to first-line enzalutamide for mCRPC would improve PSA progression-free survival. It included 162 patients with mCRPC who had not received any prior docetaxel or androgen receptor pathway inhibitors. They also had to have PSMA-positive disease and at least two out of a long list of risk factors for early progression on enzalutamide. The most common risk factors were de novo metastatic disease (52%), <3 years since diagnosis (59%), >5 bone mets (55%) and PSA doubling time <84 days (61%). The PSMA SUVmax had to be at least 15 at one of the sites, and at least 10 at larger sites of disease. PSMA uptake was too low in 18% of screened patients. Patients were randomized to receive 160mg daily enzalutamide with or without 7.5GBq of 177Lu-PSMA-617. In the later group, they received 2 cycles of 177Lu-PSMA-617 followed by an interim PSMA scan. Those with residual disease (89%) received 2 more cycles. Median PSA-PFS was significantly improved with the addition of 177Lu-PSMA-617 (13 v 7.8 months) as was clinical PFS (14 v 9.4 months). More patients had a >50% reduction in PSA with 177Lu-PSMA-617 (93% v 68%), and the rate of pain improvement was also higher (61% v 27%).
TBL: In this phase 2 trial, adding 177Lu-PSMA-617 to enzalutamide improved PSA-PFS in patients with mCRPC. | Emmett, Lancet Oncol 2024
The Study: ENZA-p was a randomized, phase 2 trial from Australia that sought to determine if adding 177Lu-PSMA-617 to first-line enzalutamide for mCRPC would improve PSA progression-free survival. It included 162 patients with mCRPC who had not received any prior docetaxel or androgen receptor pathway inhibitors. They also had to have PSMA-positive disease and at least two out of a long list of risk factors for early progression on enzalutamide. The most common risk factors were de novo metastatic disease (52%), <3 years since diagnosis (59%), >5 bone mets (55%) and PSA doubling time <84 days (61%). The PSMA SUVmax had to be at least 15 at one of the sites, and at least 10 at larger sites of disease. PSMA uptake was too low in 18% of screened patients. Patients were randomized to receive 160mg daily enzalutamide with or without 7.5GBq of 177Lu-PSMA-617. In the later group, they received 2 cycles of 177Lu-PSMA-617 followed by an interim PSMA scan. Those with residual disease (89%) received 2 more cycles. Median PSA-PFS was significantly improved with the addition of 177Lu-PSMA-617 (13 v 7.8 months) as was clinical PFS (14 v 9.4 months). More patients had a >50% reduction in PSA with 177Lu-PSMA-617 (93% v 68%), and the rate of pain improvement was also higher (61% v 27%).
TBL: In this phase 2 trial, adding 177Lu-PSMA-617 to enzalutamide improved PSA-PFS in patients with mCRPC. | Emmett, Lancet Oncol 2024