Initial clinical outcomes of ¹⁷⁷Lu-PSMA-I&T therapy in patients with metastatic castration-resistant prostate cancer (mCRPC) - Singapore experience.

Objectives: Prostate-specific membrane antigen (PSMA)- targeted radioligand therapy (RLT) is increasing used for patients with progressive metastatic castration-resistant prostate cancer (mCRPC). The objective of our pilot study is to report on the early clinical experience in Singapore.

Methods: 20 men (median age 70, range 55-92) with mCRPC were prospectively recruited after disease progression was observed whilst on standard treatments, including taxane-based chemotherapy and second-generation anti-androgens. These patients underwent screening PSMA and FDG-PET/CT scans to confirm high PSMA-expression. Once deemed eligible for treatment, they will receive up to four cycles of intravenous ¹⁷⁷Lu-PSMA-I&T at six to eight weekly intervals. These patients will be restaged 3 months following completion of treatment. The primary endpoint was PSA response (defined as greater than 50% PSA decline from baseline) and toxicity according to Common Terminology Criteria for Adverse Events (CTCAE). Additional primary endpoints were imaging and clinical responses post-treatment.

Results: Between 9 May 2018 to 31 Dec 2018, a total of 64 cycles were delivered to these patients. The mean administered radioactivity was 6.6 GBq per cycle (range 4.3 to 7.9 GBq). Three patients were still receiving ongoing treatment and only two had their 3-month restaging scans post completion of treatment. Thirteen (65%) had received at least one line of previous chemotherapy (60% docetaxel, 15% carbazitaxel, and 25% platinum-based chemotherapy), 18 (90%) received prior arbiraterone and/or enzalutamide, and six (30%) had prior Radium-223 radionuclide therapy. All had bone metastases and seven (35%) had visceral metastases. PSA decrease of more than 50% was achieved in 10 (50%) patients; with eight (40%) patients with PSA decline of more than 80%. Four out of seven patients with bone pain had improvement in pain during treatment. Of the two patients who had restaging PSMA PET/CT scan, both had significant partial response of PSMA-avid disease. Treatment-emergent grade 3 and 4 toxicities were grade 3 anaemia (15%), grade 3 thrombocytopenia (10%), grade 3 neutropenia (10%) and grade 4 neutropenia (5%). Grade 3 and 4 non-haematologic toxicities were not observed. Two patients died of disease progression within this period.

Conclusions: Our findings show that ¹⁷⁷Lu-PSMA-I&T therapy has early promising response rates and low toxicity in men with mCRPC who have progressed after conventional treatments in our local setting.