Review of 177Lu-PSMA-617 in Patients With Metastatic Castration-Resistant Prostate Cancer

Abstract

Prostate-specific membrane antigen (PSMA) is a cell membrane glycoprotein that is selectively expressed in prostate cells, with expression levels increasing dramatically in prostatic adenocarcinoma. PSMA-based radioligand therapy (RLT) has emerged as a viable therapeutic modality for the treatment of progressive metastatic prostate cancer. One commonly employed combination involves lutetium-177 conjugated to the ligand PSMA-617 (177 Lu-PSMA-617). In this meta-analysis, we examine therapeutic responses in patients with metastatic disease who have received 177 Lu-PSMA-617 therapy. We conducted a literature search with the following inclusion criteria: clinical trials involving more than 10 patients and solely utilizing 177 Lu-PSMA-617. Seventeen studies were included in the final analysis. Variables documented included the number of patients, the total therapeutic dose administered, the percentage of any prostate-specific antigen (PSA) decline, the percentage with PSA decline exceeding 50% baseline, and toxicities. Overall, a majority of patients responded to therapy, and in the prospective studies, survival was found to be upwards of one year. Significant toxicities included cytopenias, which were infrequent. Patients who had PSA declines in response to therapy had longer survival. Performance status and tumor grade were also key predictors of outcome.

Incorporating PSMA-Targeting Theranostics Into Personalized Prostate Cancer Treatment: a Multidisciplinary Perspective

“…PSMA-targeted radiotherapies are poised to offer an even more impactful alternative, being effective for both PSMA-expressing bone and soft tissue metastases ( 67 ). To date, the most tested PSMA-targeted agent is 177 Lu-PSMA-617, among other agents outlined in Table 1 , with several clinical studies showing significant treatment response, both by imaging and PSA monitoring ( 68 – 70 ). The largest randomized phase III trial comparing 177 Lu PSMA-617 to standard of care alone in 831 patients with advanced metastatic castration-resistant prostate cancer (mCRPC) (VISION) demonstrated that 177 Lu PSMA-617 significantly improves overall survival (OS, median, 15.3 vs .…”

Progress in Targeted Alpha-Particle-Emitting Radiopharmaceuticals as Treatments for Prostate Cancer Patients with Bone Metastases

“…PSMA is known to be highly expressed on prostate cancer cells at the primary tumor and within visceral and bone metastases [ 123 ]. PSMA-617, a small molecule that binds to PSMA with high affinity, was designed to target PSMA-expressing prostate cancer cells ( Figure 2 B) [ 124 ]. In a recent single-arm, single-center, phase II trial, 177 Lu-PSMA-617 was administered to men with metastatic castration-resistant prostate cancer ( n =30) [ 125 ].…”

177Lu-PSMA for advanced prostate cancer: are we ready to play big?

“…Randomized controlled trials are running to generate evidence of 177 Lu-PSMA's clinical effectiveness and safety compared to present-day treatments, such as chemotherapy, radiotherapy, and androgen blockade. The innovation also lacks evidence in different settings, such as different patient populations, cotreatment, dosage cycles, and dosage intensities [18]. Hence, the optimal valuing methods of 177 Lu-PSMA's expected benefits still have to be determined for short-and long-term cost-effectiveness analyses.…”

“…Current literature on 177 Lu-PSMA mainly focuses on its expected clinical efficacy and safety (the first and second NASSS domains) [4,6,8,18]. Based on the NASSS framework, we propose four implementation domains: (1) value proposition, (2) organizational readiness, (3) operational readiness, and (4) environmental management.…”