E4504. Safety and Efficacy of 177Lu-PSMA Radioligand Therapy in Metastatic Castration-Resistant Prostate Cancer with Diffuse Bone Metastases
  1. Cherie Ng; Singapore General Hospital
  2. Wei Ming Chua; Singapore General Hospital
  3. Charlene Tang; Singapore General Hospital
  4. Winnie Lam; Singapore General Hospital
  5. Aaron Tong; Singapore General Hospital
  6. David Ng; Singapore General Hospital
  7. Sue Ping Thang; Singapore General Hospital
Data on <sup>177</sup>Lutetium-PSMA radioligand therapy (<sup>177</sup>Lutetium-PSMA-RLT) in metastatic castrate resistant-prostate cancer (mCRPC) with extensive bone marrow involvement are limited. These patients are often excluded from trials, including the VISION trial, due to high risk of myelotoxicity and uncertain clinical benefit. Due to limited treatment options, there is a pressing need to validate <sup>177</sup>Lutetium-PSMA-RLT for this patient population. We aim to explore the efficacy and safety of <sup>177</sup>Lutetium-PSMA-RLT in patients with diffuse bone metastases detected on <sup>68</sup>Gallium-PSMA PET/CT.

Materials and Methods:
We retrospectively evaluated 48 patients with mCRPC and PSMA-avid diffuse bone metastases (50% or greater marrow involvement) who received <sup>177</sup>Lutetium-PSMA-RLT at our centre from 9 May 2018 till date. <sup>177</sup>Lutetium-PSMA-I&T was administered every 6 to 8 weeks. The primary end point was overall survival (OS), and secondary end points were prostate-specific antigen (PSA) progression-free survival (PFS), PSA response rate, clinical response (pain score), and toxicity assessment.

Patients (median age: 71 years, IQR: 66 - 76) had a median of 3.5 prior systemic treatments. They were administered a median of three cycles (IQR: 1 – 10) of <sup>177</sup>Lutetium-PSMA-RLT. The median OS and PSA PFS were 9.3 months and 3.2 months respectively. PSA response of 50% or greater was observed in 48% of patients. Patients who achieved 50% or greater PSA response had longer median OS (11.6 vs 8.6 months, <em>p</em> = 0.031) and longer median PSA PFS (6.0 vs 1.8 months, <em>p</em> < 0.0001). Pain improvement was observed in 9/21 (43%) patients Treatment was generally tolerable with mostly mild adverse events. Hematotoxicity was the most common adverse event, with 15.9%, 4.6%, and 4.6% of patients developing grade 3 or higher treatment-related anemia, neutropenia and thrombocytopenia respectively. The main limitation of this study is its retrospective design.

<sup>177</sup>Lutetium-PSMA-RLT is feasible in patients with mCRPC patients with diffuse bone metastases with comparable efficacy to existing literature and acceptable safety profile.