Beta emitter radiation therapy

The phase III, international, open label VISION study (NCT03511664) enrolled 831 patients with mCRPC previously treated with androgen receptor-directed therapy as well as taxane-based chemotherapy. Eligible patients were required to have at least one PSMA-positive lesion without a dominant PSMA-negative metastatic lesion, using approved PSMA imaging agents. Patients were randomly assigned in a 2:1 ratio to receive either 177Lu-PSMA-617 every 6 weeks for four to six cycles plus protocol-permitted standard care or standard care alone. Standard care included abiraterone, enzalutamide, bisphosphonates, radiation therapy, denosumab, and/or glucocorticoids and excluded chemotherapy, immunotherapy, 223Ra, and investigational drugs when the trial was designed (e.g., olaparib). Alternate primary end points included image-based PFS and OS.[79]

The phase III, international, open label VISION study (NCT03511664) enrolled 831 patients with mCRPC previously treated with androgen receptor-directed therapy as well as taxane-based chemotherapy. Eligible patients were required to have at least one PSMA-positive lesion without a dominant PSMA-negative metastatic lesion, using approved PSMA imaging agents. Patients were randomly assigned in a 2:1 ratio to receive either 177Lu-PSMA-617 every 6 weeks for four to six cycles plus protocol-permitted standard care or standard care alone. Standard care included abiraterone, enzalutamide, bisphosphonates, radiation therapy, denosumab, and/or glucocorticoids and excluded chemotherapy, immunotherapy, 223Ra, and investigational drugs when the trial was designed (e.g., olaparib). Alternate primary end points included image-based PFS and OS.[79]

The median follow-up was 20.9 months. The median image-based PFS was 8.7 months in the 177Lu-PSMA-617-plus-standard care group and 3.4 months in the standard care-alone group (HRprogression or death, 0.40; 99.2% CI, 0.29–0.57; P < .001). The median OS was 15.3 months in the 177Lu-PSMA-617-plus-standard care group and 11.3 months in the standard care-alone group (HRdeath, 0.62; 95% CI, 0.52–0.74; P < .001).[79][Level of evidence A1]

The phase III, international, open label VISION study (NCT03511664) enrolled 831 patients with mCRPC previously treated with androgen receptor-directed therapy as well as taxane-based chemotherapy. Eligible patients were required to have at least one PSMA-positive lesion without a dominant PSMA-negative metastatic lesion, using approved PSMA imaging agents. Patients were randomly assigned in a 2:1 ratio to receive either 177Lu-PSMA-617 every 6 weeks for four to six cycles plus protocol-permitted standard care or standard care alone. Standard care included abiraterone, enzalutamide, bisphosphonates, radiation therapy, denosumab, and/or glucocorticoids and excluded chemotherapy, immunotherapy, 223Ra, and investigational drugs when the trial was designed (e.g., olaparib). Alternate primary end points included image-based PFS and OS.[79]

All key secondary end points significantly favored the 177Lu-PSMA-617-plus-standard care group, including median time to first symptomatic skeletal event or death (11.5 months vs. 6.8 months; HR, 0.50; 95% CI, 0.40–0.62; P < .001).

The phase III, international, open label VISION study (NCT03511664) enrolled 831 patients with mCRPC previously treated with androgen receptor-directed therapy as well as taxane-based chemotherapy. Eligible patients were required to have at least one PSMA-positive lesion without a dominant PSMA-negative metastatic lesion, using approved PSMA imaging agents. Patients were randomly assigned in a 2:1 ratio to receive either 177Lu-PSMA-617 every 6 weeks for four to six cycles plus protocol-permitted standard care or standard care alone. Standard care included abiraterone, enzalutamide, bisphosphonates, radiation therapy, denosumab, and/or glucocorticoids and excluded chemotherapy, immunotherapy, 223Ra, and investigational drugs when the trial was designed (e.g., olaparib). Alternate primary end points included image-based PFS and OS.[79]

The most common adverse events in the 177Lu-PSMA-617-plus-standard care group were fatigue, dry mouth, and nausea, nearly all of which were grade 1 or 2 in severity. Grade 3 or higher adverse events occurred in 52.7% of patients in the 177Lu-PSMA-617-plus-standard care group and 38% of patients in the standard care-alone group. The most common grade 3 or higher adverse event in the 177Lu-PSMA-617-plus-standard care group was anemia (12.9% vs. 4.9% in the standard care-alone group).

The phase III, international, open label VISION study (NCT03511664) enrolled 831 patients with mCRPC previously treated with androgen receptor-directed therapy as well as taxane-based chemotherapy. Eligible patients were required to have at least one PSMA-positive lesion without a dominant PSMA-negative metastatic lesion, using approved PSMA imaging agents. Patients were randomly assigned in a 2:1 ratio to receive either 177Lu-PSMA-617 every 6 weeks for four to six cycles plus protocol-permitted standard care or standard care alone. Standard care included abiraterone, enzalutamide, bisphosphonates, radiation therapy, denosumab, and/or glucocorticoids and excluded chemotherapy, immunotherapy, 223Ra, and investigational drugs when the trial was designed (e.g., olaparib). Alternate primary end points included image-based PFS and OS.[79]

There was delayed worsening of heath-related QOL in the 177Lu-PSMA-617-plus-standard care group versus the standard care-alone group, including FACT-P scores (HR, 0.54; 0.45–0.66), BPI-SF pain intensity scores (HR, 0.52; 0.42–0.63), and EQ-5D-5L utility scores (HR, 0.65; 0.54–0.78).[80]