¹⁷⁷Lu-EB-PSMA radioligand therapy with escalating doses in patients with metastatic castration-resistant prostate cancer

Purpose: This study is designed to assess the safety and therapeutic response to¹⁷⁷Lu-EB-PSMA treatment with escalating doses in patients with metastatic castration-resistant prostate cancer (mCRPC).

Methods: With institutional review board approval and informed consent, patients were randomly divided into three groups: Group A (n=10) were treated with 1.18 ± 0.09 GBq/dose of ¹⁷⁷Lu-EB-PSMA. Group B (n=10) were treated with 2.12± 0.19 GBq/dose of ¹⁷⁷Lu-EB-PSMA. Group C (n=8) were treated with 3.52 ± 0.58 GBq/dose of ¹⁷⁷Lu-EB-PSMA. Eligible patients received up to three cycles of ¹⁷⁷Lu-EB-PSMA therapy, at eight weekly intervals. Adverse events were categorized using the Common Toxicity Criteria for Adverse Events 4.0. The response data were determined using ⁶⁸Ga-PSMA PET/CT and PSA response.

Results: Due to disease progression or bone marrow suppression, 4 of 10, 5 of 10, and 5 of 10 patients completed three cycles therapy as planned in Group A, B, and C, respectively. The PSA response was correlated with treatment dose, with PSA disease control rates (partial response + stable disease) in Group B (70%) and C (75%) being significantly higher than that in Group A (10%) (P=0.007), but without significant difference between Group B and Group C (P=1.00). ⁶⁸Ga-PSMA PET/CT showed significant response in all the treatment groups: the change of SUVmax were -36.00±23.35% (P=0.00), -38.63±42.57% (P=0.00), and -33.83±39.63% (P=0.00) after one cycle treatment, respectively; -35.48±29.06% (P=0.001), -30.50±19.86% (P=0.00), and -51.67±24.97% (P=0.00) after 2 cycles treatment, respectively; -42.12±21.44% (P=0.009), -51.85±14.05% (P=0.00), and -45.01±42.07% (P=0.002) after 3 cycles treatment, respectively. However, there was no significant difference among the three groups (P varies from 0.088 to 0.895). Hematologic toxicity study found that platelets in Group B (-56.8±17.5%) and Group C (-56.1±11.1%) decreased more than those in Group A (-4.3±52.7%), and that Grade 4 thrombocytopenia occurred in 2 (25.0%) patients in Group C. No serious nephritic or hepatic side effects were observed.

Conclusions: This study demonstrates that 2.12 GBq/dose of ¹⁷⁷Lu-EB-PSMA seems to be the best choice in balancing safety with adequacy in tumor treatment. Further investigations with increased number of patients are warranted. Figure legend: Waterfall graphs of PSA responses as compared to baseline levels after each cycle of treatment for the three groups (A, C, E). PSA increase 100% was cropped due to simplification. The representative patients for ⁶⁸Ga-PSMA PET/CT and PSA response evaluation in Group A (B), Group B (D) and Group C (F).

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