FDA Approval Summary: Lutetium Lu 177 Vipivotide Tetraxetan for Patients with Metastatic Castration-Resistant Prostate Cancer

Abstract

On March 23, 2022, the United States Food and Drug Administration (FDA) approved Pluvicto (lutetium Lu 177 vipivotide tetraxetan, also known as 177Lu-PSMA-617) for the treatment of adult patients with prostate-specific membrane antigen (PSMA)-positive metastatic castration-resistant prostate cancer (mCRPC) who have been treated with androgen receptor pathway inhibition and taxane-based chemotherapy. The recommended 177Lu-PSMA-617 dose is 7.4 gigabecquerels (GBq; 200 mCi) intravenously every 6 weeks for up to 6 doses, or until disease progression or unacceptable toxicity. The FDA granted traditional approval based on VISION (NCT03511664), which was a randomized (2:1), multicenter, open-label trial that assessed the efficacy and safety of 177Lu-PSMA-617 plus best standard of care (BSoC) (n=551) or BSoC alone (n=280) in men with progressive, PSMA-positive mCRPC. Patients were required to have received ≥1 androgen receptor pathway inhibitor, and 1 or 2 prior taxane-based chemotherapy regimens. There was a statistically significant and clinically meaningful improvement in overall survival (OS) with a median OS of 15.3 months in the 177Lu-PSMA-617 plus BSoC arm and 11.3 months in the BSoC arm, respectively (Hazard ratio: 0.62, 95% CI: 0.52, 0.74, p<0.001). The most common adverse reactions (≥20%) occurring at a higher incidence in patients receiving 177Lu-PSMA-617 were fatigue, dry mouth, nausea, anemia, decreased appetite, and constipation. The most common laboratory abnormalities that worsened from baseline in ≥30% of patients receiving 177Lu-PSMA-617 were decreased lymphocytes, decreased hemoglobin, decreased leukocytes, decreased platelets, decreased calcium, and decreased sodium. This article summarizes the FDA review of data supporting traditional approval of 177Lu-PSMA-617 for this indication.

2022 FDA TIDES (Peptides and Oligonucleotides) Harvest

“…Serious adverse effects were observed in 36% of patients, whereas 2.8% of patients who had concurrent treatment-related thrombocytopenia experienced fatal adverse reactions [ 35 ]. In another study, lutetium 177 Lu vipivotide tetraxetan was compared with cabazitaxel, which is a type of chemotherapy for the treatment of prostate cancer [ 36 , 37 ].…”

Theranostic Nuclear Medicine with Gallium-68, Lutetium-177, Copper-64/67, Actinium-225, and Lead-212/203 Radionuclides

“…In 2022, the FDA (USA) approved [ 177 Lu]Lu-(PSMA-617) (also known as lutetium-177 vipivotide tetraxetan and Pluvicto) for the "treatment of adult patients with prostate-specific membrane antigen (PSMA)-positive metastatic castration-resistant prostate cancer (mCRPC) who have been treated with androgen receptor pathway inhibition and taxane-based chemotherapy". 94 [ 177 Lu]Lu(PSMA-617) was originally developed by researchers at The German Cancer Research Center and University Hospital Heidelberg, Germany. 95 The molecule contains a glutamate-ureido-lysine motif, but the linker between the pharmacophore and the DOTA chelator was systematically optimized to improve tumor uptake and internalization as well as pharmacokinetic properties.…”

“…This led to the development of PSMA targeting molecules containing the Glu-NH-CO-NH-Lys motif but where the HBED-CC chelator (Figure a) was replaced with DOTA, which forms stable complexes with [ 177 Lu]­Lu III (Figure a). In 2022, the FDA (USA) approved [ 177 Lu]­Lu­(PSMA-617) (also known as lutetium-177 vipivotide tetraxetan and Pluvicto) for the “treatment of adult patients with prostate-specific membrane antigen (PSMA)-positive metastatic castration-resistant prostate cancer (mCRPC) who have been treated with androgen receptor pathway inhibition and taxane-based chemotherapy” . [ 177 Lu]­Lu­(PSMA-617) was originally developed by researchers at The German Cancer Research Center and University Hospital Heidelberg, Germany .…”

Selective ablation of TRA-1-60+ pluripotent stem cells suppresses tumor growth of prostate cancer

“…Typically, patients are treated with docetaxel and later cabazitaxel. Recently, [ 177 Lu]Lu-PSMA-617, the first prostate-specific membrane antigen (PSMA)-selective radiopharmaceutical therapy (RPT) was approved for patients with disease progression following first-line taxane treatment 14 . The findings demonstrated an absolute overall survival benefit of approximately ~ 4 months compared with protocol-defined standard-of-care 15 .…”