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Review
. 2024 Mar 7;31(3):1400-1415.
doi: 10.3390/curroncol31030106.

177Lu-PSMA-617 in Metastatic Castration-Resistant Prostate Cancer: A Review of the Evidence and Implications for Canadian Clinical Practice

Kim N Chi  1 , Steven M Yip  2 , Glenn Bauman  3 , Stephan Probst  4 , Urban Emmenegger  5 , Christian K Kollmannsberger  1 , Patrick Martineau  6 , Tamim Niazi  7 , Frédéric Pouliot  8   9 , Ricardo Rendon  10 , Sebastien J Hotte  11 , David T Laidley  12 , Fred Saad  13   14
Affiliations
Review

177Lu-PSMA-617 in Metastatic Castration-Resistant Prostate Cancer: A Review of the Evidence and Implications for Canadian Clinical Practice

Kim N Chi et al. Curr Oncol. .

Abstract

Prostate-specific membrane antigen (PSMA) is highly expressed in prostate cancer and a therapeutic target. Lutetium-177 (177Lu)-PSMA-617 is the first radioligand therapy to be approved in Canada for use in patients with metastatic castration-resistant prostate cancer (mCRPC). As this treatment represents a new therapeutic class, guidance regarding how to integrate it into clinical practice is needed. This article aims to review the evidence from prospective phase 2 and 3 clinical trials and meta-analyses of observational studies on the use of 177Lu-PSMA-617 in prostate cancer and discuss how Canadian clinicians might best apply these data in practice. The selection of appropriate patients, the practicalities of treatment administration, including necessary facilities for treatment procedures, the assessment of treatment response, and the management of adverse events are considered. Survival benefits were observed in clinical trials of 177Lu-PSMA-617 in patients with progressive, PSMA-positive mCRPC who were pretreated with androgen receptor pathway inhibitors and taxanes, as well as in taxane-naïve patients. However, the results of ongoing trials are awaited to clarify questions regarding the optimal sequencing of 177Lu-PSMA-617 with other therapies, as well as the implications of predictive biomarkers, personalized dosimetry, and combinations with other therapies.

Keywords: 177Lu vipivotide tetraxetan; 177Lu-PSMA-617; mCRPC; prostate cancer; radioligand therapy.

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Conflict of interest statement

G.B. has received compensation from Advanced Accelerator Applications/Novartis and the Ontario Institute for Cancer Research. K.N.C. has served as a consultant and received honoraria from Advanced Accelerator Applications/Novartis, Astellas Pharma, AstraZeneca, Genentech/Roche, Janssen, Merck, Pfizer, and POINT Biopharma, and received grants and research funding from Advanced Accelerator Applications/Novartis, AstraZeneca, Genentech/Roche, Janssen, Pfizer, and POINT Biopharma. U.E. has received personal fees for serving as an advisor/consultant for Advanced Accelerator Applications/Novartis, Amgen, Astellas Pharma, AstraZeneca, Bayer, Ferring Pharmaceuticals, Janssen, Knight Therapeutics, Merck, and Pfizer, research funding from Astellas Pharma, Bayer, and Janssen, and institutional funding for the conduct of clinical studies from Advanced Accelerator Applications/Novartis, Astellas Pharma, AstraZeneca, Bayer, Genentech/Roche, Janssen, Merck, and POINT Biopharma. S.J.H. has received honoraria for advisory activities and has conducted research with funding paid to the institution from Advanced Accelerator Applications/Novartis. C.K.K. has received honoraria for presentations from Astellas Pharma, Bayer, Bristol-Myers Squibb, Eisai, Ipsen, Janssen, Merck, Pfizer, and Seagen, and for ad-hoc advisory boards from Advanced Accelerator Applications/Novartis, Astellas Pharma, Bayer, BioNTech, Bristol-Myers Squibb, Eisai, Ipsen, Janssen, Merck, Pfizer, Seagen, and Sanofi. D.T.L. has participated in advisory meetings for Advanced Accelerator Applications/Novartis, Bayer, and Ipsen, has participated in research studies sponsored by Advanced Accelerator Applications/Novartis, POINT Biopharma, and Progenics, and has received consultancy fees from Advanced Accelerator Applications/Novartis and Ipsen. P.M. has served as a consultant and received honoraria from Advanced Accelerator Applications/Novartis. T.N. has received research/educational funding from AbbVie, Amgen, Astellas Pharma, AstraZeneca, Bayer, Janssen, Sanofi, TerSera, and Tolmar, and honoraria from AbbVie, Advanced Accelerator Applications/Novartis, Amgen, Astellas Pharma, AstraZeneca, Bayer, Ferring Pharmaceuticals, Janssen, Knight Therapeutics, Merck, Sanofi, TerSera, and Tolmar. F.P. has received honoraria and/or was a consultant for AbbVie, Advanced Accelerator Applications/Novartis, Amgen, Astellas Pharma, AstraZeneca, Bayer, Janssen, Merck, Sanofi, TerSera, and Tolmar. S.P has received speaking and consulting fees from Advanced Accelerator Applications/Novartis, Bayer, and POINT Biopharma. R.R. has served on advisory boards and speaker bureaus for AbbVie, Amgen, Astellas Pharma, AstraZeneca, Bayer, Ferring Pharmaceuticals, Janssen, McKesson, Sanofi, and TerSera, and has participated in clinical trials funded by Advanced Accelerator Applications/Novartis, Astellas Pharma, AstraZeneca, Bayer, Ferring Pharmaceuticals, Janssen, Myovant Sciences, Pfizer, POINT Biopharma, and Sanofi. F.S. has acted in a consulting/advisory role for and received honoraria from AbbVie, Advanced Accelerator Applications/Novartis, AstraZeneca, Astellas Pharma, Bayer, Janssen, Merck, Pfizer, and Tolmar, and has conducted research with funding paid to the institution from Advanced Accelerator Applications/Novartis, AstraZeneca, Astellas Pharma, Bayer, Janssen, Merck, and Pfizer. S.M.Y. has received consultant, advisory board, or sponsorship honoraria from Advanced Accelerator Applications/Novartis, AstraZeneca, Bayer, Bristol-Myers Squibb, Genentech/Roche, Ipsen, Janssen, Merck, OncoHelix, and Pfizer. Financial support for medical writing assistance was provided by Novartis Pharmaceuticals Ltd. Canada. The funder had no role in the design of the study, in the collection, analyses, or interpretation of the data, in the writing of the manuscript, or in the decision to publish the results.

Figures

Figure 1
Figure 1
PRISMA flow diagram of literature review. ASCO, American Society of Clinical Oncology; ASCO-GU, American Society of Clinical Oncology Genitourinary Cancers; ESMO, European Society for Medical Oncology; PRISMA, Preferred Reporting Items for Systematic Reviews and Meta-Analyses; SNMMI, Society of Nuclear Medicine and Molecular Imaging.
Figure 2
Figure 2
Adverse events most commonly increased in patients treated with 177Lu-PSMA-617 + SOC vs. SOC alone in the phase 3 VISION trial (Δ ≥ 10%) [24]. LuPSMA, 177Lu-PSMA-617; SOC, standard of care.
Figure 3
Figure 3
Adverse events most commonly increased in patients treated with 177Lu-PSMA-617 vs. ARPI change in the phase 3 PSMAfore trial (Δ ≥ 5%) [27]. ARPI, androgen receptor pathway inhibitor; LuPSMA, 177Lu-PSMA-617.
Figure 4
Figure 4
PSMA PET/CT selection criteria for the VISION trial [44]. A version of this figure was originally published in JNM. Kuo PH, Benson T, Messmann R, Groaning M. Why we did what we did: PSMA PET/CT selection criteria for the VISION trial. J Nucl Med 2022, 63, 816–818. © SNMMI [44]. CT, computed tomography; MIP, maximum intensity projection; MR, magnetic resonance; PET, positron emission tomography; PSMA, prostate-specific membrane antigen.
See this image and copyright information in PMC

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