Men with severe prostate cancer discontinue Pluvicto treatment in a real-world setting at rates that far exceed those seen in clinical trials, according to a study published January 5 in Clinical Genitourinary Cancer.
The finding is from an analysis of patients treated at Ghaem Hospital in Mashhad, Iran, and underscores the need to optimize patient selection and improve outcomes, noted lead author Mohammad Hadi Samadi, MD, of Mashhad University of Medical Sciences, and colleagues.
“While Lu-177 PSMA-617 offers meaningful clinical benefit, a substantial proportion of patients do not complete the full course, underscoring the critical need to predict nonresponders and potential discontinuers prior to treatment,” the group wrote.
Lutetium-177 prostate-specific membrane antigen-617 (Lu-177 PSMA-617) (Pluvicto, Novartis) was approved in 2022 based on its performance in several clinical trials in men with metastatic castration-resistant prostate cancer (mCRPC). In these trials, participants underwent a median of five treatment cycles, and approximately 50% discontinued treatment, primarily due to disease progression and toxicity, the authors wrote.
Real-world data suggest higher attrition, yet detailed predictors of early cessation and survival impact remain limited, they added. To bridge the knowledge gap, the researchers aimed to characterize discontinuation reasons, timing, predictive factors, and survival impact in a real-world cohort.
The group analyzed outcomes among 208 patients with mCRPC treated at their hospital between 2017 and 2024. They defined discontinuation as stopping treatment before the recommended six cycles, and categorized reasons as disease progression, serious adverse events, patient-related factors, physician decision, death, or miscellaneous. They further defined early discontinuation as stopping before completing three cycles.
According to the results, 81.2% of patients discontinued treatment before six cycles (median, 3 cycles), with disease progression (43.8%) and serious adverse events (21.9%, mainly hematologic) as leading causes. In addition, 44.2% of patients discontinued early (<3 cycles), and this was independently predicted by higher Gleason scores, lower hemoglobin, and lower platelets, while baseline creatinine and Alkaline phosphatase (ALP) levels predicted overall discontinuation.
Finally, treatment discontinuation independently worsened overall survival, with early discontinuers surviving only five months versus 20 months for others, Samadi and colleagues reported.
“These findings underscore the need for pre-treatment risk stratification using Gleason score, hemoglobin, platelets, renal function, and ALP to identify patients at high risk of early failure,” the group wrote.
The study authors noted that there was a lack of uniform imaging follow-ups among the patients in the study. Thus, some patients with more frequent or timely scans may have been diagnosed with radiographic progression earlier, leading to premature discontinuation, while others may have received additional cycles due to delayed imaging.
Additionally, the lack of detailed molecular profiling, quantitative PSMA tumor volume, or standard uptake value measurements on baseline imaging data restricted the study’s insights into biological factors that could be driving discontinuation, the researchers wrote.
“Future prospective studies with multicenter cohorts are needed to validate our findings and explore molecular predictors of treatment response and discontinuation, such as PSMA-PET/CT-based biomarkers,” the group concluded.
The full study is available here.