In analyses from the phase III PSMAfore trial reported in The Lancet Oncology, Fizazi et al examined whether [177Lu]Lu–PSMA-617 (vipivotide tetraxetan; Lu-PSMA) improved patient-reported outcomes and delayed the time to first symptomatic skeletal events vs change of androgen receptor pathway (ARP) inhibitor in taxane-naive patients with prostate-specific membrane antigen (PSMA)-positive metastatic castration-resistant prostate cancer who experienced disease progression on a previous ARP inhibitor.
In the primary analysis of the trial, Lu-PSMA significantly improved radiographic progression–free survival compared with change of ARP inhibitor in these patients.
Study Details
In the open-label international trial, 468 patients were randomly assigned between June 2021 and October 2022 to receive Lu-PSMA at 7.4 GBq every 6 weeks for six cycles (n = 234) or change in ARP inhibitor (n = 234; abiraterone or enzalutamide per local labeling). Patients were candidates for a change in ARP inhibitor after disease progression on a previous ARP inhibitor. Secondary endpoints featured in the current analysis included the time to worsening in self-reported health-related quality of life, assessed by Functional Assessment of Cancer Therapy–Prostate (FACT-P) and EQ-5D-5L, and pain was assessed by Brief Pain Inventory–Short Form (BPI-SF), and the time to first symptomatic skeletal event. The current analyses were performed at the third interim analysis of overall survival.
Key Findings
Median follow-up from randomization to the third interim analysis data cutoff (in February 2024) was 24.11 months (interquartile range [IQR] = 20.24–27.60 months) in the Lu-PSMA group and 24.13 months (IQR = 20.24–27.37 months) in the group that had a change in ARP inhibitor.
The Lu-PSMA group had a delayed time to worsening vs the group that had a change in ARP inhibitor in all assessed FACT-P, EQ-5D-5L, and BPI-SF scales and subscales. The median time to worsening in FACT-P total score was 7.5 months (95% confidence interval [CI] = 6.1–8.5 months) in the Lu-PSMA group vs 4.3 months (95% CI = 3.5–4.5 months) in the group that had a change in ARP inhibitor (hazard ratio [HR] = 0.61, 95% CI = 0.50–0.75). The median time to worsening in EQ-5D-5L utility score was 6.3 months (95% CI = 4.7–7.9 months) vs 3.9 months (95% CI = 3.3–4.4 months; HR = 0.67, 95% CI = 0.54–0.82). The median time to worsening of BPI-SF pain intensity was 5.0 months (95% CI = 4.4–6.8 months) vs 3.6 months (95% CI = 3.1–4.4; HR = 0.72, 95% CI = 0.59–0.88).
The median time to first symptomatic skeletal event was not reached (95% CI = not estimable to not estimable) in the Lu-PSMA group vs 18.0 months (95% CI = 14.3 months to not estimable) in the group that had a change in ARP inhibitor (HR = 0.41, 95% CI = 0.26–0.63).
Overall, grade ≥ 3 adverse events occurred in 36% of the Lu-PSMA group vs 48% of the group that had a change in ARP inhibitor, most commonly anemia (6% vs 7%). One treatment-related death occurred, as a result of a cerebrovascular accident in a patient in the group that had a change in ARP inhibitor.
The investigators concluded: “[177Lu]Lu–PSMA-617 might delay worsening of patient-reported outcomes and prevent symptomatic skeletal events versus ARP [inhibitor] change in taxane-naive patients with PSMA-positive metastatic castration-resistant prostate cancer whose disease has progressed once on a previous ARP [inhibitor].”
Karim Fizazi, MD, of the Institut Gustave Roussy and Centre Oscar Lambret, Universite Paris-Saclay, Villejuif, France, is the corresponding author of The Lancet Oncology article.
Disclosure: The study was funded by Novartis. For full disclosures of all study authors, visit The Lancet Oncology.
