Dr Sartor on Efficacy and Safety of Lutetium Lu 177 Vipivotide Tetraxetan in Taxane-Naive mCRPC

Oliver Sartor, MD, director, radiopharmaceutical trials, Mayo Clinic, discusses updated efficacy findings from the phase 3 PSMAfore trial (NCT04689828) of lutetium Lu 177 vipivotide tetraxetan (Pluvicto; formerly 177Lu-PSMA-617) in patients with previously treated, taxane-naive metastatic castration-resistant prostate cancer (mCRPC).

The open-label, multicenter randomized study compared the efficacy of lutetium Lu 177 vipivotide tetraxetan with standard-of-care treatment with an androgen receptor pathway inhibitior (ARPI), Sartor begins. All patients on the study were required to confirmed mCRPC, have progressed on a prior second-generation ARPI, and be eligible for treatment with a second-line ARPI. Other eligibility criteria included the presence of metastatic disease, and confirmed PSMA PET positivity. Patients were randomly assigned to receive either lutetium Lu 177 vipivotide tetraxetan or an ARPI that they did not receive in the first-line setting.

Data from the second interim analysis of PSMAfore showed that patients treated with lutetium Lu 177 vipivotide tetraxetan experienced prolonged radiographic progression-free survival (rPFS) vs treatment with an an ARPI, with a hazard ratio of 0.43 (95% CI, 0.33-0.54), Sartor reports. The median rPFS with lutetium Lu 177 vipivotide tetraxetan was 12.02 months (95% CI, 9.30-14.42) vs 5.59 months (95% CI, 4.17-5.95) with an ARPI, he adds. Moreover, patients on the lu 177 vipivotide tetraxetan arm experienced an objective response rate of 50.7% (95% CI, 38.6%-62.8%) vs 14.9% (95% CI, 7.7%-25.0%) in the ARPI arm.

An analysis of the trial’s secondary end points showed that the hazard ratio for the crossover-adjusted overall survival (OS) was 0.80 (95% CI, 0.48-1.33), Sartor continues. As the range between confidence intervals surpassed 1, this result was not deemed statistically significant, he explains. Additional assessments of health-related quality of life, time to prostate-specific antigen (PSA) progression, time to pain progression, PSA decline rate, and objective response, all favored lutetium Lu 177 vipivotide tetraxetan, Sartor details.

The incidence of grade 3/4 adverse events (AEs) and dose adjustments were notably lower with lutetium Lu 177 vipivotide tetraxetan compared with secondary hormonal therapy, Sartor states, adding that this was an unexpected finding. Discontinuation rates were low, at 5% in both treatment arms, he adds. These findings underscore the favorable safety and efficacy profile of lutetium Lu 177 vipivotide tetraxetan across a spectrum of clinical end points, Sartor concludes.