Abstract
PurposePreliminary data from retrospective analyses and recent data from large randomized controlled trials suggest safety and efficacy of radioligand therapy (RLT) targeting prostate-specific membrane antigen (PSMA) in men with metastatic castration-resistant prostate cancer (mCRPC). Limited data on this modality have been published regarding large samples treated in everyday practice.MethodsWe analyzed prospectively collected registry data regarding lutetium-177 (177Lu)-PSMA-617 RLT of 254 consecutive men with mCRPC seen in everyday academic practice. Since 177Lu-PSMA-617 was experimental salvage treatment following failure of individually appropriate conventional therapies, patients were generally elderly and heavily pretreated (median age 70 years; prior taxanes 74.0%, 188/254), with late–end-stage disease (visceral metastasis in 32.7%, 83/254). Primary endpoints were response to RLT, defined by changes from baseline serum prostate-specific antigen (PSA) concentration, PSA progression-free survival (PSA-PFS), and overall survival (OS), estimated with Kaplan–Meier statistics, and caregiver-reported and patient-reported safety. Unless noted, median (minimum–maximum) values are given.ResultsPatients received 3 (1–13) 177Lu-PSMA-617 activities (6.5 [2.5–11.6] GBq/cycle) every 5.7 (3.0–11.0) weeks. Best response was ≥ 50% PSA reduction in 52.0% of patients (132/254). PSA-PFS was 5.5 (95% confidence interval [95%CI] 4.4–6.6) months and OS, 14.5 (95%CI 11.5–17.5) months. In multivariable Cox proportional-hazards modeling, response to the initial ≤ 2 RLT administrations was the strongest significant prognosticator related to OS (hazard ratio 3.7 [95%CI 2.5–5.5], p < 0.001). No RLT-related deaths or treatment discontinuations occurred; the most frequent RLT-related Grade 3/4 adverse events were anemia (18/254 patients, 7.1%), thrombocytopenia (11/254, 4.3%), and lymphopenia (7/254, 2.8%). RLT-related xerostomia, all grade 1/2, was noted in 53/254 (20.9%).ConclusionsIn a large, prospectively observed “real-world” cohort with late-stage/end-stage mCRPC and conventional treatment failure, 177Lu-PSMA-617 RLT was effective, safe, and well-tolerated. Early biochemical disease control by such therapy was associated with better OS. Prospective study earlier in the disease course may be warranted.
Highlights
Treatment options to extend disease control and survival in patients with metastatic castration-resistant prostate carcinoma have expanded dramatically in the past two decades [1,2,3,4]
Additional details regarding the radioligand therapy (RLT) regimen are given in Supplementary Table S2
At 4–6 weeks after the first cycle, prostate-specific antigen (PSA) concentration had declined from baseline levels in 169/254 patients (66.5%, 95% confidence interval (CI) 60.5–72.1%), with a ≥ 50% decline in 77/254 (30.3%, 95%CI 25.0–36.2%)
Summary
Treatment options to extend disease control and survival in patients with metastatic castration-resistant prostate carcinoma (mCRPC) have expanded dramatically in the past two decades [1,2,3,4]. MCRPC remains lethal and new therapies continue to be much-needed [5]. For this reason, radioligand therapy (RLT) targeting prostate-specific membrane antigen (PSMA) has attracted interest as a potential treatment for mCRPC [6,7,8,9,10,11,12,13,14]. PSMA is heterogeneously expressed in an array of benign and malignant extraprostatic tissues as well as in prostatic tissue [15,16,17,18,19,20,21]. Expression typically is orders of magnitude greater in cancerous versus healthy prostatic tissue
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