Lutetium ¹⁷⁷Lu Vipivotide Tetraxetan Efficacy and Toxicity in Advanced Prostate Cancer

This retrospective study aimed to evaluate the efficacy and toxicity of lutetium ¹⁷⁷Lu vipivotide tetraxetan ([LuVT], Pluvicto, Novatis Pharmaceutical Corporation), a peptide receptor radionuclide therapy, in metastatic castration-resistant prostate cancer patients treated at a single institution during the first year of Food and Drug Administration-approved clinical use.

A total of 45 patients with metastatic castration-resistant prostate cancer and positive prostate-specific membrane antigen positron emission tomography imaging were treated with at least 1 cycle of LuVT therapy between September 2022 and September 2023. Clinical records were reviewed to assess prostate-specific antigen (PSA) response, imaging outcomes, and patient-reported and physician-reported toxicities. PSA responses were classified into complete, excellent (≥50% reduction), partial (10%-49% reduction), no response, and initial response with disease progression. Toxicities were graded with Common Terminology Criteria for Adverse Events v5.0 criteria.

Of 45 patients, 44 encompassed the final cohort (1 excluded after a single treatment before death from comorbidity). The mean age was 72.8 years and 88.9% of the cohort was White. A total of 68.9% of the cohort observed PSA biomarker improvement of ≥10%, and 55.6% with ≥50% PSA reduction. Three patients (6.7%) achieved a complete response. Imaging improvements were seen in 8 patients, including 1 with non-PSA-secreting disease. Adverse events were predominantly grade 1 and 2 severities. Most common patient-reported effects included fatigue and flare-related bone pain, with flare reactions noted in 26.7% of patients. None of the toxicities exceeded grade 2 severity. Treatment discontinuation occurred in 33.3% of patients because of a combination of progression, toxicity, lab parameters, or palliative care transition.

LuVT therapy demonstrated consistent efficacy and tolerable toxicity in this real-world cohort, with results comparable to the VISION trial. Flare pain reactions and appetite loss emerged as prominent, although tolerable, adverse effects. Limitations include small sample size, lack of long-term follow-up, and a homogenous population with significantly advanced disease.