Lutetium Lu 177 vipivotide tetraxetan for metastatic castration-resistant prostate cancer

ABSTRACT

Introduction

¹⁷⁷Lu-vipivotide tetraxetan is a radiopharmaceutical that selectively targets prostate-specific membrane antigen (PSMA) and delivers beta-radiations to kill prostate cancer cells.

Areas covered

Extensive experience outside the United States as well as randomized phase II and phase III data demonstrate that ¹⁷⁷Lu-vipivotide tetraxetan is a safe, generally well tolerated, and effective therapy for men with mCRPC. ¹⁷⁷Lu-vipivotide tetraxetan was approved by the FDA in March 2022 for the treatment of PSMA-positive metastatic castration-resistant prostate cancer (mCRPC) after androgen receptor pathway inhibition and taxane-based chemotherapy based on the results of the VISION trial.

Expert opinion

This review discusses the development and studies leading to the approval of ¹⁷⁷Lu-vipivotide tetraxetan. In all, ¹⁷⁷Lu-vipivotide tetraxetan is an exciting new tool in the arsenal for men with mCRPC after novel androgen pathway inhibitors and at least one taxane chemotherapy. Optimal selection of patients, sequencing of ¹⁷⁷Lu-vipivotide tetraxetan with the other agents available to treat mCRPC, and the use of dosimetry are current areas of interest with great potential and opportunities for further individual patient optimization using the tools of theranostics.

KEYWORDS:

• Lutetium-177
• prostate cancer
• PSMA-617
• ¹⁷⁷Lu-vipivotide tetraxetan

Article highlights

• ¹⁷⁷Lu-vipivotide tetraxetan is a radiopharmaceutical that selectively targets prostate-specific membrane antigen (PSMA) and delivers beta-radiations to kill prostate cancer cells.

• Extensive experience using ¹⁷⁷Lu-vipivotide tetraxetan outside the United States prior to the FDA approval and the positive results of the phase III, international VISION study confirm the efficacy of ¹⁷⁷Lu-vipivotide tetraxetan for the treatment of PSMA-positive metastatic castrate-resistant prostate cancer (mCRPC) in the late-line setting after novel androgen receptor pathway inhibitors and at least one chemotherapy.

• With clinical outcome benefits including overall survival, imaging-based progression-free survival, and time to skeletal-related events, all on the order of about 3–4 months, ¹⁷⁷Lu-vipivotide tetraxetan represents another drug in the armamentarium of treatment for men with mCRPC.

• There is much to learn and many opportunities for individual patient optimization using the tool of theranostics, including findings on screening PSMA-PET/CT scans and dosimetry.

Information resources

Further information regarding ¹⁷⁷Lu-vipivotide tetraxetan can be found by reading the primary sources of the pivotal German Society of Nuclear Medicine retrospective study [55] as well as the TheraP [59] and VISION [61] studies. The Journal of Nuclear Medicine Dosimetry Supplement in December 2021 includes multiple reviews on dosimetry, including major references related to dosimetry for ¹⁷⁷Lu-vipivotide tetraxetan. Finally, Song et al. reviewed PSMA theranostics for mCRPC [86].

Declaration of interest

H Jacene has served as a consultant for; Advanced Accelerator Applications, Blue Earth Diagnostics, Spectrum Dynamics, has received research support from: Blue Earth Diagnostics and received royalties from Cambridge University Press.

G Sonpavde has served on the advisory board of; Bristol Myers Squibb, Genentech, EMD Serono, Merck, Sanofi, Seattle Genetics/Astellas, Astrazeneca, Exelixis, Janssen, Bicycle Therapeutics, Pfizer, Gilead, Scholar Rock, G1 Therapeutics, Eli Lilly/Loxo Oncology, Infinity Pharmaceuticals, Lucence Health, IMV, Vial and Syapse. G Sonpavde has also served as a consultant and on the scientific Advisory Board of Suba Therapeutics, has received institutional research support from Sanofi (iaward), Astrazeneca, Gilead, Helsinn, Lucence, Predicine, BMS, EMD Serono, Jazz Therapeutics, and Genecentric, has served as a speaker for BIO – INFORMAÇÃO BRASILEIRA DE ONCOLOGIA Ltda, OLE Forum (Mexico), Seagen, has received data safety monitoring committee honorarium from Mereo,has received writing/editor fees from Uptodate, Cancer Expert Now, Editor of Elsevier Practice Update Bladder Cancer Center of Excellence and his spouse is employed by Myriad.

The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper received no funding.