Rapid Readouts: Results from the Phase 3 VISION Study

A. Oliver Sartor, MD, discusses data from the following presentation:

• Phase 3 study of 177Lu-PSMA-617 in patients with metastatic castration-resistant prostate cancer (VISION) (Morris, ASCO 2021, LBA4)
  • The objective of this study is to report results from the phase 3 VISION study (NCT03511664) of 177Lu-PSMA-617 in patients with metastatic castration-resistant prostate cancer (mCRPC).
  • 177Lu-PSMA-617 is a targeted radioligand therapy that delivers β-particle radiation to mCRPC lesions that highly express prostate-specific membrane antigen (PSMA).
  • Men with PSMA-positive mCRPC previously treated with androgen receptor pathway inhibitors and 1 to 2 taxane regimens were randomly assigned 2:1 to either 177Lu-PSMA-617 (7.4 GBq every 6 weeks x 4 to 6 cycles) plus standard of care (SOC) vs SOC alone (investigator determined but excluded cytotoxic chemotherapy and radium-223).
  • Alternate primary end points were radiographic progression-free survival (rPFS) using Prostate Cancer Clinical Trials Working Group 3 criteria by independent central review, and overall survival (OS).
  • Key secondary end points were objective response rate (ORR; RECIST v1.1), disease control rate (DCR), and time to first symptomatic skeletal event (SSE).
  • Conclusions: efficacy
    • 177Lu-PSMA-617 plus SOC significantly improved median rPFS vs SOC alone (median rPFS, 8.7 vs 3.4 months; HR, 0.40 [99.2% CI, 0.29-0.57]; P < .001, one-sided) in the rPFS analysis set (n=581).
    • Median OS was also significantly improved versus SOC alone (median OS, 15.3 vs 11.3 months; HR, 0.62 [95% CI, 0.52-0.74]; P < .001, one-sided) in the OS analysis set (n=831).
    • Key secondary end points were statistically significant between the treatment arms in favor of 177Lu-PSMA-617 plus SOC, including ORR (29.8% vs 1.7%), DCR (89.0% vs 66.7%), and time to first SSE (median time, 11.5 vs 6.8 months; HR, 0.50).
  • Conclusions: safety
    • A higher rate of high-grade treatment-emergent adverse events was observed with 177Lu-PSMA-617 (52.7% vs 38.0).
    • Fatigue, bone marrow suppression, dry mouth, and nausea and vomiting were the highest all grade and grade 3-5 treatment-emergent adverse events in both study arms.
• 177Lu-PSMA-617 plus SOC is a well-tolerated regimen that improves rPFS and prolongs OS compared with SOC alone in men with PSMA-positive mCRPC.