Data from the phase III PSMAfore trial were presented during a Presidential Symposium at the European Society for Medical Oncology (ESMO) Congress 2023 (Abstract LBA13). Results showed that the trial of lutetium Lu-177 vipivotide tetraxetan met its primary endpoint, with a clinically meaningful and statistically significant benefit in radiographic progression–free survival in patients with prostate-specific membrane antigen (PSMA)-positive metastatic castration-resistant prostate cancer after previous treatment with androgen receptor pathway inhibitor(ARPI) therapy, compared to a change in ARPI (abiraterone or enzalutamide).
“The radiographic progression–free survival data are impressive and the treatment effect is comparable with what was observed in the VISION trial,” said Oliver Sartor, MD, PSMAfore Co–Principal Investigator, Chairman of the Trial Steering Committee, and Director, Radiopharmaceutical Trials, Mayo Clinic, Rochester, Minnesota—one of the many sites where the trial was conducted. “We look forward to a future where [lutetium Lu-177 vipivotide tetraxetan] may be a viable therapy for patients in need of alternative, earlier options.”
Oliver Sartor, MD
About the PSMAfore Study
PSMAfore (ClinicalTrials.gov identifier NCT04689828) is a phase III, open-label, multicenter, 1:1 randomized study comparing the efficacy and safety of Lu-177 vipivotide tetraxetan to a change in ARPI (abiraterone or enzalutamide) in patients with PSMA-positive metastatic castration-resistant prostate cancer who have not been exposed to a taxane-containing regimen. Patients enrolled must have progressed only once after receiving a second-generation ARPI (abiraterone, enzalutamide, darolutamide, or apalutamide).
Patients randomly assigned to the change in the ARPI arm were allowed to cross over to receive Lu-177 vipivotide tetraxetan upon confirmation of radiographic progression by blinded independent central review. There were 469 participants enrolled in the study.
The primary endpoint is radiographic progression–free survival, defined as the time from random assignment to radiographic progression by Prostate Cancer Clinical Trials Working Group 3–modified Response Evaluation Criteria in Solid Tumors version 1.1 (as assessed by blinded independent central review) or death. The key secondary endpoint of overall survival is defined as the time from date of random assignment until the date of death due to any cause. The prespecified crossover-adjusted overall survival analysis was performed using the rank-preserving structural failure time model to adjust for crossover.
Results Presented at the ESMO Congress 2023
The trial met its primary endpoint of radiographic progression–free survival, with a 59% reduction in the risk of radiographic disease progression in patients with Lu-177 vipivotide tetraxetan vs a change of ARPI. Using a data cutoff with a median of 8.6 months longer study follow-up, an updated radiographic progression–free survival analysis (hazard ratio [HR] = 0.43, 95% confidence interval [CI] = 0.33%–0.54%) demonstrated a consistent clinical benefit in patients taking Lu-177 vipivotide tetraxetan vs change in ARPI, more than doubling time to radiographic disease progression (12.0 months vs 5.6 median months).
Patients taking Lu-177 vipivotide tetraxetan also showed improved quality of life, maintaining their Functional Assessment of Cancer Therapy-Prostate total score for 3 months longer than a change in ARPI (7.5 vs 4.3 months), with a delay in worsening pain (BPI-SF) of 5.0 vs 3.7 months. Other clinically meaningful efficacy endpoints also favored Lu-177 vipivotide tetraxetan, with a prostate-specific antigen decline of at least 50% being more than 2.5 times more frequent with Lu-177 vipivotide tetraxetan than with a change in ARPI.
At the second interim overall survival analysis with 45% of events, the prespecified crossover-adjusted overall survival analysis demonstrated a hazard ratio of 0.80 (95% CI = 0.48–1.33). The unadjusted intent-to-treat overall survival analysis was confounded as 84% of patients who discontinued ARPI due to radiographic progression crossed over to receive Lu-177 vipivotide tetraxetan. The trial will continue to assess overall survival, with the next interim overall survival analysis expected in 2024.
The most frequently reported all-grade adverse events for Lu-177 vipivotide tetraxetan were primarily grade 1 and 2 and included dry mouth (in 57.3% of patients), asthenia (in 31.7%), nausea (in 31.3%), anemia (in 24.2%) and fatigue (in 22.9%).
Disclosure: For full disclosures of the study authors, visit cslide.ctimeetingtech.com/esmo2023.
