The 177Lu-PSMA-617 is a targeted radioligand therapy that distributes ß–particle radiation to cells expressing PSMA and to the surrounding microenvironment
During the ASCO World Congress 2021, VISION (NCT03511664), an international, randomized, open-label phase III trial evaluating 177Lu-PSMA-617 in men with PSMA-positive metastatic castration-resistant prostate cancer (mCRPC), previously treated with new-generation androgen inhibitors and/or one to two regimens with taxanes, was presented.
PSMA positivity (threshold higher than liver) was determined by the central review of 68Ga-PSMA-11 tests. Patients were randomized in a 2:1 ratio to receive 177Lu-PSMA-617 (7.4GBq every six weeks for six cycles) plus standard of care (SOC) versus SOC alone. SOC was determined by the investigator but excluded cytotoxic chemotherapy and radium-223. The alternative primary endpoints were radiographic progression-free survival (rPFS) by independent central review (ICR) and overall survival (OS). In the alternative hypothesis, the median rPFS was assumed to be six months for a HR of 0.67 and the median OS was assumed as 13.7 months for a HR of 0.7306. The main secondary endpoints included the objective response rate (ORR) by RECIST v1.1, the disease control rate (DCR) and the time to first symptomatic skeletal event (SSE).
Findings:
Between June 4, 2018, and October 23, 2019, 831 out of 1,179 selected patients were randomized in a 2:1 ratio to receive 177Lu-PSMA-617 + SOC (n = 551) or SOC alone (n = 280). The study’s mean follow-up was 20.9 months at the data cut-off date (January 27, 2021). The treatment groups were balanced in terms of demographic data and baseline characteristics.
The 177Lu-PSMA-617 + SOC significantly improved rPFS versus SOC alone (8.7 vs 3.4 months; HR 0.40; CI 99.2% 0.29 – 0.57]; p < 0.001, unilateral). The alternative primary endpoint of OS was also significantly better versus SOC alone (15.3 vs 11.3 months; HR 0.62; 95% CI 0.52 – 0.74; p < 0.001 unilateral).
All major secondary outcomes were statistically significant between treatment arms in favor of 177Lu-PSMA-617 + SOC, including ICR-determined ORR (29.8% vs 1.7%), ICR-determined DoR (89.0% vs 66.7%) and time for the first SSE (11.5 vs 6.8 months; HR, 0.50).
Although a higher rate of high-grade treatment-emergent adverse events was observed with 177Lu-PSMA-617 (52.7% vs. 38.0%), therapy was well tolerated.
The authors conclude that treatment with 177Lu-PSMA-617 plus SOC is a well-tolerated regimen that improves rPFS and prolongs OS compared to SOC alone in men with advanced-stage PSMA-positive mCRPC, supporting its adoption as a standard of care.