Clinical outcome of standardized 177Lu-PSMA-617 therapy in metastatic prostate cancer patients receiving 7400 MBq every 4 weeks

• Published in: European journal of nuclear medicine and molecular imaging Vol. 47; no. 3; pp. 713 - 720
• Main Authors: Rasul, Sazan, Hacker, Marcus, Kretschmer-Chott, Elisabeth, Leisser, Asha, Grubmüller, Bernhard, Kramer, Gero, Shariat, Shahrokh, Wadsak, Wolfgang, Mitterhauser, Markus, Hartenbach, Markus, Haug, Alexander R.
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01-03-2020; Springer Nature B.V
• Subjects: Anemia; Cardiology; Castration; Hemoglobin; Imaging; Intervals; Leukocytes; Leukopenia; Lutetium isotopes; Medicine; Medicine & Public Health; Metastases; Metastasis; Nuclear Medicine; Oncology; Oncology – Genitourinary; Original; Original Article; Orthopedics; Patients; Platelets; Prostate cancer; Radiology; Receiving; Reduction; Statistical models; Survival; Therapy; Toxicity; mCRPC; PSMA PET; PSMA therapy; Prostate cancer; PSA response
• ISSN: 1619-7070; 1619-7089
• DOI: 10.1007/s00259-019-04584-1

Purpose
[
177
Lu]Lu-PSMA-617 radio-ligand therapy (PSMA-RLT) is emerging in patients with an advanced metastatic castration-resistant prostate cancer (mCRPC). Here, we aimed to estimate the results of PSMA-RLT in terms of response, progression-free survival (PFS), and overall survival (OS) in patients receiving a highly standardized treatment regimen due to mCRPC. The toxicity of PSMA-RLT has also been evaluated.
Patients and methods
Fifty-four patients (mean age 72 ± 7 years, median PSA at time of initial therapy 66 [range 1.0–4890 μg/L]), receiving three PSMA-RLT cycles (mean 7315 ± 573 MBq) at four weekly intervals, were included in this retrospective analysis. Hematological and biochemical parameters were regularly determined in every patient. Kaplan-Meier estimates were used to assess PFS and OS and a Cox proportional hazard model was used to analyze significant associations. Treatment response was based on PSA measurements 4 weeks after the 3rd treatment.
Results
The majority of patients were previously treated with abiraterone/enzalutamide (69%) and docetaxel/cabazitaxel (67%). In total, 79% of the patients showed a decrease in PSA (median PSA decrease from 66 to 19.8, range 0.7–4563 μg/L,
P
< 0.001) 1 month after the 3rd therapy cycle. Among them, 58% and 35% demonstrated a PSA-decline of > 50% and > 80%, respectively. Median OS was 119 weeks; median PFS was 25 weeks. Patients presenting with a PSA decline had significantly longer PFS (27 vs. 15 weeks,
P
< 0.0001) and OS (median survival not reached vs. 52 weeks,
P
< 0.001) than patients with no PSA reduction. Moreover, patients with reduction in PSA levels ≥ 50% (median survival not reached vs. 52 weeks,
P
< 0.0001) and ≥ 80% (median survival not reached vs. 87 weeks,
P
= 0.008) lived significantly longer. While hemoglobin did not change during treatment, levels of platelets (236 ± 71 g/L vs. 193 ± 67 g/L) and leucocytes (6.5, range 2.9–13.7 g/L vs. 4.8, range 1.5–12.3 g/L) decreased significantly, both
P
< 0.001. Two grade 3 leukocytopenia and one grade 3 anemia were observed.
Conclusion
Intense PSMA-RLT regime with four weekly intervals between the cycles is well-tolerated and offers favorable response rates, PFS, and survival rates for patients with mCRPC.