Across contemporary clinical trials, Pluvicto (lutetium-177 [Lu-177] prostate-specific membrane antigen [PSMA]-617) consistently prolongs progression-free survival for patients, according to research presented February 17 at a symposium in Palm Desert, CA.
“The consistency of progression-free survival benefit with favorable tolerability was striking,” Mohammad Ganiyani, a postdoctoral research fellow at the Miami Cancer Institute, told attendees. The research was delivered at the American Society for Radiation Oncology’s (ASTRO) inaugural Multidisciplinary Radiopharmaceutical Therapy Symposium.
Lu-177 PSMA-617 was approved in 2022 for men with metastatic castration-resistant prostate cancer (mCRPC). The treatment is a type of radioligand therapy (RLT) and offers a distinct mechanism beyond androgen-signaling inhibition, with pivotal trials showing improved progression-free survival for patients with favorable tolerability.
Yet as its clinical use expands, comparative evidence with established systemic therapies such as hormone-based drugs remains limited, Ganiyani noted. Thus, he and colleagues performed a systematic review and meta-analysis to evaluate Lu-177 PSMA-617 in mCRPC compared with standard-of-care systemic therapy.
Out of 456 studies screened, the researchers identified seven phase II and III trials that met their eligibility criteria for the final analysis. A total of 2,526 patients were involved in the trials, including 1,365 in the Lu-177 PSMA-617 arms (median age, 70.8) and 1,161 in the standard-of-care arms (mean age, 71.8).
The researchers analyzed and compared data on progression-free survival, overall survival, and grade ≥3 adverse events (AEs).
According to the pooled results, Lu-177 PSMA-617 significantly improved progression-free survival compared with controls (pooled hazard ratio [HR] = 0.64; p < 0.001). No significant difference was observed in overall survival (HR = 0.91; p = 0.55). The pooled risk ratio for grade ≥ 3 AEs was 0.98 (p = 0.75), with no significant difference in AEs between groups.
“Lu-177 PSMA-617 has a 36% relative reduction in risk of progression versus standard therapies,” Ganiyani said.
The finding of no difference in overall survival between groups likely reflects postprogression and salvage use of Lu-177 PSMA-617 (after cancer progressed) in control arms in some trials, as well as disease and trial heterogeneity, Ganiyani noted. In addition, he said that thrombocytopenia emerged as the primary hematologic toxicity, which highlights the need for careful baseline marrow assessment and close platelet monitoring during therapy.
“The data collectively reinforce Lu-177 PSMA-617 as a well-tolerated, effective radioligand option for advanced mCRPC, warranting continued integration into earlier disease settings and combination strategies,” Ganiyani said.
ASTRO’s Multidisciplinary Radiopharmaceutical Therapy Symposium continues through February 18.