Oncology
Metastatic Prostate Cancer
Gaining Experience With Prostate-Specific Membrane Antigen–Directed Radioligand Therapy
Overview
Reports from the 2023 Society of Nuclear Medicine & Molecular Imaging (SNMMI) Annual Meeting included early institutional experiences with 177Lu-PSMA-617 (also known as lutetium Lu 177 vipivotide tetraxetan) for the treatment of metastatic castration-resistant prostate cancer (mCRPC).
Conference Reporter Editor-in-Chief Tom Iarocci, MD, previewed several presentations from the conference, summarizing important findings here.
Tom Iarocci, MD
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“PSMA-targeted RLT is a relatively recent development in the treatment of mCRPC, and clinicians are now integrating this option into clinical practice."
Prostate-specific membrane antigen (PSMA)–targeted radioligand therapy (RLT) is a relatively recent development in the treatment of mCRPC, and clinicians are now integrating this option into clinical practice. On March 23, 2022, the US Food and Drug Administration (FDA) approved 177Lu-PSMA-617 for the treatment of progressive PSMA-positive mCRPC. The FDA also approved a complementary gallium-68–based agent that is indicated for positron emission tomography of PSMA-positive lesions.
The FDA approval of 177Lu-PSMA-617 was based on the pivotal phase 3 VISION trial, in which patients with pretreated PSMA-positive mCRPC who received 177Lu-PSMA-617 plus standard of care (SOC) had a statistically significant reduction in risk of death. The VISION trial included a late-line population (ie, patients could have had multiple lines of therapy and usually had at least 2 to 3 prior lines). The addition of 177Lu-PSMA-617 to best SOC therapy led to an overall improvement in the dual primary end point of radiographic progression-free survival and overall survival.
Recently, Fizazi et al published an update from the VISION trial with additional findings, reporting that 177Lu-PSMA-617 plus SOC delayed time to worsening in health-related quality of life and time to skeletal events compared with SOC alone. These results support the use of 177Lu-PSMA-617 in individuals with mCRPC who received previous androgen receptor pathway inhibitor therapy and taxane treatment.
At the 2023 SNMMI Annual Meeting, several reports focused on 177Lu-PSMA RLT, including both 177Lu-PSMA-617 and 177Lu-PSMA-I&T. While both agents are currently being evaluated in ongoing trials, only 177Lu-PSMA-617 is FDA approved at this time.
Representing the Icahn School of Medicine at Mount Sinai, Novello et al shared their institutional experience with 177Lu-PSMA-617 in poster P1168. They noted limitations of their data analysis and the early preliminary stage of their reporting, but concluded that, overall, their observations support the use of 177Lu-PSMA-617 as an emerging treatment option for mCRPC. Additionally, they noted that their experience with 177Lu-PSMA-617 was that it is safe and effective, with rates and severity of hematotoxicity events that are similar to those in the published literature. In their presentation, Abdelrahman and colleagues, also from Mount Sinai, noted the importance of monitoring hematologic laboratory values to predict the need for transfusion support and intervention, when necessary (P318).
Finally, Tuchayi et al shared data from the University of California, San Francisco, at this year's SNMMI meeting, stating that their initial experience with 177Lu-PSMA-617 mirrors the results that were observed in the VISION trial, with a PSA50 response rate (ie, the proportion of patients who achieve at least a 50% reduction in prostate-specific antigen) of 62% and an objective response rate of 40% (P1222). The most common side effects were anemia and leukopenia.
As clinicians gain experience with this new treatment, professional resources are also emerging that may help with its integration into clinical practice. The joint European Association of Nuclear Medicine/SNMMI procedure guideline for the use of 177Lu‐PSMA‐RLT was recently published by Kratochwil and colleagues. Goals for this guideline include to help clinicians select patients with the highest potential to benefit from 177Lu-PSMA-RLT, perform the procedure in accordance with current best practice, and prepare for possible side effects and their clinical management.
References
Abdelrahman A, Kulkarni R, Akinlusi R, et al. Correlation between the total osseus tumor volume and the development of hematologic toxicities in patients with metastatic castrate-resistant prostate cancer receiving 177Lu-PMSA-617 [poster P318]. Poster presented at: 2023 Society of Nuclear Medicine & Molecular Imaging Annual Meeting; June 24-27, 2023; Chicago, IL.
Fizazi K, Herrmann K, Krause BJ, et al. Health-related quality of life and pain outcomes with [177Lu]Lu-PSMA-617 plus standard of care versus standard of care in patients with metastatic castration-resistant prostate cancer (VISION): a multicentre, open-label, randomised, phase 3 trial. Lancet Oncol. 2023;24(6):597-610. doi:10.1016/S1470-2045(23)00158-4
Kratochwil C, Fendler WP, Eiber M, et al. Joint EANM/SNMMI procedure guideline for the use of 177Lu-labeled PSMA-targeted radioligand-therapy (177Lu-PSMA-RLT). Eur J Nucl Med Mol Imaging. 2023 May 29. doi:10.1007/s00259-023-06255-8
Novello M, Abdelrahman A, Cengiz TB, et al. Initial experience with lutetium177-PSMA-617 for metastatic or biochemically recurrent prostate cancer: a single institution review [poster P1168]. Poster presented at: 2023 Society of Nuclear Medicine & Molecular Imaging Annual Meeting; June 24-27, 2023; Chicago, IL.
Sartor O, de Bono J, Chi KN, et al; VISION Investigators. Lutetium-177-PSMA-617 for metastatic castration-resistant prostate cancer. N Engl J Med. 2021;385(12):1091-1103. doi:10.1056/NEJMoa2107322
Tuchayi AM, Kim ST, Morley A, et al. Initial experience with 177Lu-PSMA-617 therapy: toxicity and outcomes post-approval [poster P1222]. Poster presented at: 2023 Society of Nuclear Medicine & Molecular Imaging Annual Meeting; June 24-27, 2023; Chicago, IL.
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