In an analysis from the phase III VISION trial reported in The Lancet Oncology by Karim Fizazi, MD, PhD, and colleagues, the addition of lutetium (Lu-177) vipivotide tetraxetan to standard of care was associated with improved health-related quality of life in patients with prostate-specific membrane antigen (PSMA)-positive, metastatic, castration-resistant prostate cancer.
The trial supported the March 2022 approval of Lu-177 vipivotide tetraxetan for patients with PSMA-positive metastatic castration-resistant prostate cancer who have received treatment with an androgen receptor pathway inhibitor and taxane-based chemotherapy.
Karim Fizazi, MD, PhD
Study Details
In the open-label trial, 831 patients from nine countries in North America and Europe were randomly assigned 2:1 between June 2018 and October 2019 to receive Lu-177 vipivotide tetraxetan plus standard of care or standard of care alone. The current analysis included 581 patients randomly assigned to Lu-177 vipivotide tetraxetan plus standard of care (n = 385) or standard of care (n = 196) during or after March 2019. Lu-177 vipivotide tetraxetan was given via infusions of 7.4 GBq every 6 weeks for four cycles, plus two optional cycles. Standard of care included approved hormonal treatments, bisphosphonates, and radiotherapy.
In the overall population, the Lu-177 vipivotide tetraxetan group had significantly improved radiographic progression-free and overall survival. The current analysis included assessment of health-related quality of life with the Functional Assessment of Cancer Therapy-Prostate (FACT-P) score and EQ-5D-5L utility score, assessment of pain with the Brief Pain Inventory-Short Form (BPI-SF), and evaluation of time to first symptomatic skeletal event or death.
Key Findings
Median time to first symptomatic skeletal event or death was 11.5 months (95% confidence interval [CI] = 10.3–13.2 months) in the Lu-177 vipivotide tetraxetan group vs 6.8 months (95% CI = 5.2– 8.5 months) in the control group (hazard ratio [HR] = 0.50, 95% confidence interval [CI] = 0.40–0.62).
Median time to worsening of ≥ 10 points on the FACT-P score, clinical disease progression, or death was 5.7 months (95% CI = 4.8–6.6 months) vs 2.2 months (95% CI = 1.8–2.8 months; HR = 0.54, 95% CI = 0.45–0.66, P < .001).
Median time to worsening of ≥ 30% or ≥ two points on the BPI-SF scale, clinical disease progression, or death was 6.9 months (95% CI = 6.0–7.7 months) vs 2.6 months (95% CI = 2.1–3.1 months; HR = 0.52, 95% CI = 0.42–0.63, P < .001).
Median time to worsening in EQ-5D-5L utility score—defined as time to any decrease relative to baseline or no change from baseline—was 1.0 months (95% CI = 0.7–1.8 months) vs 0.5 months (95% CI = 0.4–1.0 months; HR = 0.65, 95% CI = 0.54–0.78, P < .001).
Among the patients included in the current analysis, treatment-related adverse events led to death in five patients in the Lu-177 vipivotide tetraxetan group (due to pancytopenia in two, bone marrow failure in one, subdural hematoma in one, and intracranial hemorrhage in one) and no patients in the control group.
The investigators concluded, “[Lu-177 vipivotide tetraxetan] plus standard of care delayed time to worsening in [health-related quality of life] and time to skeletal events compared with standard of care alone. These findings support the use of [Lu-177 vipivotide tetraxetan] in patients with metastatic castration-resistant prostate cancer who received previous androgen receptor pathway inhibitor and taxane treatment.”
Dr. Fizazi, of the Department of Cancer Medicine, Institut Gustave Roussy, University of Paris Saclay, Villejuif, is the corresponding author for The Lancet Oncology article.
Disclosure: The study was funded by Advanced Accelerator Applications (Novartis). For full disclosures of the study authors, visit thelancet.com.
