Addition of 177Lu-PSMA-617 therapy to standard of care for patients with metastatic castration-resistant prostate cancer (mCRPC) significantly improves survival, according to results from the randomized, phase 3 VISION trial.
Despite recent therapeutic advances, mCRPC remains invariably fatal. Prostate-specific membrane antigen (PSMA) is highly expressed in mCRPC lesions. 177Lu-PSMA-617 is a targeted radioligand therapy that delivers β-particle radiation to PSMA-expressing cells and surrounding microenvironment. The VISION trial (NCT03511664) is an international, randomized, open-label, phase 3 study evaluating 177Lu-PSMA-617 in men with PSMA-positive mCRPC, previously treated with next-generation androgen receptor signaling inhibition and 1–2 taxane regimens.
A total of 831 patients were randomized 2:1 to 177Lu-PSMA-617 (7.4 GBq every 6 weeks x 6 cycles) plus standard of care versus standard of care alone (investigator determined but excluding cytotoxic chemotherapy and radium-223). The alternate primary endpoints were radiographic progression-free survival and overall survival. Key secondary endpoints were objective response rate, disease control rate, and time to first symptomatic skeletal event. Dr Michael Morris (Memorial Sloan Kettering Cancer Center, NY, USA) presented the results of the VISION trial after a median follow up of 20.9 months . Addition of 177Lu-PSMA-617 therapy to standard of care significantly improved median radiographic progression-free survival versus standard of care alone: 8.7 months versus 3.4 months. The alternate primary endpoint of overall survival was also significantly improved versus standard of care: median overall survival was 15.3 versus 11.3 months in patients treated with 177Lu-PSMA-617 plus standard of care versus patients treated with standard of care alone.
All key secondary endpoints were statistically significant between the treatment arms in favor of 177Lu-PSMA-617 plus standard of care, including overall response rate (51.0% vs 3.1%) and disease control rate (86.3% vs 50.0%). While a higher rate of high-grade treatment-emergent adverse events was observed with 177Lu-PSMA-617 (any grade: 85.3% vs 28.8%; grade 3-5: 28.4% vs 3.9%), therapy was in general well tolerated. Based on these results, Dr Morris concluded that “177Lu-PSMA-617 plus standard of care treatment is a well-tolerated regimen that improves both radiographic progression-free survival and overall survival compared with standard of care alone in men with advanced-stage PSMA-positive mCRPC. This supports its adoption as a standard of care.”
- Morris MJ, et al. Phase III study of lutetium-177-PSMA-617 in patients with metastatic castration-resistant prostate cancer (VISION). ASCO 2021 Virtual Meeting, abstract LBA4.