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Efficacy and safety of 177Lu-labeled prostate-specific membrane antigen radionuclide treatment in patients with diffuse bone marrow involvement: a multicenter retrospective study

  • Andrei Gafita 1,
  • Wolfgang P. Fendler 2,
  • Wang Hui 7,
  • Shahneen Sandhu 8,
  • Manuel Weber 2,
  • Rouzbeh Esfandiari 4,
  • Jeremie Calais 5,
  • Isabel Rauscher 1,
  • Hendrik Rathke 6,
  • Robert Tauber 7,
  • Ebrahim S. Delpassand 4,
  • Wolfgang A. Weber 1,
  • Ken Herrmann 2,
  • Johannes Czernin 5,
  • Matthias Eiber 1,
  • Michael S. Hofman 8
1 Department of Nuclear Medicine, Technical University Munich, Klinikum rechts der Isar, Munich, Germany 2 Department of Nuclear Medicine, University of Duisburg-Essen and German Cancer Consortium (DKTK)-University Hospital Essen, Essen, Germany 3 Department of Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia 4 Excel Diagnostics and Nuclear Oncology Center, Houston, TX, USA 5 Ahmanson Translational Theranostics Division, Department of Molecular and Medical Pharmacology, University of California Los Angeles, Los Angeles, CA, USA 6 Department of Nuclear Medicine, Heidelberg University Hospital, Heidelberg, Germany 7 Department of Urology, Technical University Munich, Klinikum rechts der Isar, Munich, Germany 8 Department of Molecular Imaging and Therapeutic Nuclear Medicine, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia

The 177Lu-labeled prostate-specific membrane antigen (LuPSMA) radionuclide therapy for metastatic castration-resistant prostate cancer is under investigation in a phase III trial (VISION: NCT03511664). However, patients with diffuse bone involvement, diagnosed with a “superscan” by bone scintigraphy at baseline, were excluded due to a lack of efficacy and safety data. We therefore aimed to investigate the feasibility of LuPSMA in patients with diffuse bone marrow involvement on baseline PSMA-targeted positron emission tomography. The primary end points were prostate-specific antigen (PSA) response (Prostate Cancer Working Group 3 [PCWG3]), hematologic safety profile (Common Terminology Criteria for Common Adverse Events [CTCAE]), and overall survival. Secondary end points of quality of life (assessed with Brief Pain Inventory-Short Form questionnaires) and radiologic response (Response Evaluation Criteria in Solid Tumors [RECIST]) were assessed. Through retrospective screening of databases, we identified 43 eligible patients across four centers worldwide who received 154 cycles of LuPSMA under clinical trials or compassionate access programs. Median baseline PSA was 1000 (interquartile range 431–2151) ng/ml. PSA decline of at least 50% at 12 wk was achieved in 22 (58%) patients, while median time to pain progression was 8.3 (95% confidence interval [CI] 4.1–12.6) mo. Median overall survival was 11.6 (95% CI 8.8–14.3) mo. Objective response in nodal or visceral disease was reported in seven (39%) of 18 patients with RECIST measurable disease. Grade 3 anemia, thrombocytopenia, and neutropenia occurred in nine (22%), seven (17%), and three (8%) patients, respectively. Grade 4 thrombocytopenia was noticed in three (8%) patients. In conclusion, patients with diffuse bone marrow involvement demonstrated similar LuPSMA efficacy and safety to phase II evidence. Acceptable safety outcomes do not support exclusion of patients with a superscan from future LuPSMA treatment protocols.

Commented by Dr. Roderick van den Bergh

Radionuclide therapy using 177Lu-labeled prostate-specific membrane antigen (LuPSMA) has entered the arena for treating metastatic castration-resistant prostate cancer relatively recently. Different ongoing trials assess the efficacy and safety of this promising therapy. In order to reduce expected side effects, patients with diffuse bone metastasis are generally excluded from the clinical trials. However, evidence on efficacy and safety of this treatment in the most unfavorable cases is also needed.

Gafita et al report on 43 patients from six centres with >50% axial bone marrow involvement as identified on PSMA-PET/CT who receive LuPSMA. Of these patients, 2/3 had three or more previous lines of therapy, median PSA was 1000 ng/ml, and 1/3 had visceral involvement, thus having very high disease burden. A total of 56% received four or more cycles of LuPSMA. Twenty-two patients (58%) had a PSA decline of >=50%, and these patients had a longer median overall survival (12.5 mo vs 5.4 mo) than subjects whose PSA did not respond favorably. Half of the patients with pain reported an improvement in symptoms. Eight (19%) of patients discontinued treatment due to hematologic events. Grade 3-4 anemia, thrombocytopenia, or neutropenia that was probably or definitely related to LuPSMA (i.e. not related to disease progression) occurred in 8%, 8%, and 3%, respectively. Patients with low trombocytes or neutrophils had a higher chance of developing thrombocytopenia and neutropenia, respectively. These adverse event rates were similar to percentages reported in previous studies including patients with lower disease burden.

LuPSMA has importantly expanded the options for patients with metastatic castration-resistant prostate cancer. Its position within the treatment sequence of these patients and possible combinations with chemotherapy and/or androgen-receptor targeted agents still needs to be established. Gafita et al show that also in patients with a high disease burden, who were heavily pretreated with different previous lines, with diffuse bone metastasis, and in whom little other treatment options are available, LuPSMA is effective and with a safety profile similar to previous reports. Considering this data, patients in the final stage of prostate cancer should not be denied LuPSMA, provided they have a favorable hematologic profile.