On March 23, 2022, the radioligand therapeutic agent lutetium Lu-177 vipivotide tetraxetan was approved for treatment of patients with prostate-specific membrane antigen (PSMA)-positive metastatic castration-resistant prostate cancer who have been treated with an androgen receptor pathway inhibitor and taxane-based chemotherapy.¹

The U.S. Food and Drug Administration simultaneously approved gallium Ga-68 gozetotide, a radioactive diagnostic agent for positron-emission tomography of PSMA-positive lesions, for selection of patients for Lu-177 vipivotide tetraxetan treatment.

Supporting Efficacy Data

Approval was based on findings in the open-label VISION trial (ClinicalTrials.gov identifier NCT03511664). Patients were randomly assigned 2:1 to receive Lu-177 vipivotide tetraxetan at 7.4 GBq (200 mCi) every 6 weeks for up to a total of six doses plus best standard of care (n = 551) or best standard of care alone (n = 280).

The trial showed significant improvements in overall survival and radiographic progression-free survival. Median overall survival was 15.3 months (95% confidence interval [CI] = 14.2–16.9 months) with Lu-177 vipivotide tetraxetan vs 11.3 months (95% CI = 9.8–13.5 months) with best standard of care (hazard ratio = 0.62, 95% CI = 0.52–0.74, P < .001). Interpretation of the magnitude of the radiographic progression-free survival benefit was limited due to the high degree of censoring from early dropout in the control group.

How It Is Used

Patients must be selected for treatment using Ga-68 gozetotide or another approved PSMA-11 imaging agent.

The recommended dose is 7.4 GBq (200 mCi) intravenously every 6 weeks for up to six doses or until disease progression or unacceptable toxicity. Product labeling provides instructions for dosage modification, including dose reduction, for adverse events including myelosuppression, renal toxicity, dry mouth, gastrointestinal toxicity, fatigue, electrolyte or metabolic abnormalities, aspartate or alanine aminotransferase elevation, and other nonhematologic toxicities.

Safety Profile

In the VISION trial, the most common adverse events of any grade with Lu-177 vipivotide tetraxetan were fatigue (43%), dry mouth (39%), nausea (35%), anemia (32%), decreased appetite (21%), and constipation (20%). The most common grade 3 or 4 adverse events included anemia (13%), thrombocytopenia (8%), and fatigue (6%). The most common grade 3 or 4 laboratory abnormalities were decreased lymphocytes (47%) and decreased hemoglobin (15%). Safety follow-up was not sufficient to capture late radiation-associated toxicities.

Serious adverse events occurred in 36% of patients, most commonly hemorrhage (4%), musculoskeletal pain (3.8%), and sepsis (3.2%). Adverse events led to discontinuation of treatment in 12%, most commonly anemia (2.8%) and thrombocytopenia (2.8%). Fatal adverse events occurred in 2.8% of patients, including sepsis, pancytopenia, hepatic failure, intracranial hemorrhage, subdural hematoma, ischemic stroke, COVID-19, and aspiration pneumonia.

Lu-177 vipivotide tetraxetan has warnings/precautions for risk from radiation exposure, myelosuppression, renal toxicity, embryofetal toxicity, and infertility. 

REFERENCE

1. Pluvicto (lutetium Lu-177 vipivotide tetraxetan) injection, for intravenous use, prescribing information, Advanced Accelerator Applications USA, Inc, a Novartis company, March 2022. Available at https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/215833s000lbl.pdf. Accessed October 31, 2022.