Clinical outcomes of 177lutetium-prostate-specific membrane antigen therapy in advanced prostate cancer—a prospective pilot study in an Asian population

Abstract

Objective Metastatic castration-resistant prostate cancers are aggressive tumors with poor prognosis. Prostate-specific membrane antigen-targeted radionuclide therapy is a potential treatment for these patients. Here, we report our initial experience in Singapore. Methods Twenty men (median age 70) with progressive disease were prospectively recruited. Prostate-specific membrane antigen and fluorodeoxyglucose-PET/computed tomography were performed to confirm high prostate-specific membrane antigen-expression. Up to four cycles of 177lutetium-prostate-specific membrane antigen-I&T at 6–8 weekly intervals were administered. Patients were restaged 3 months following treatment. Primary endpoints were prostate-specific antigen decline ≥50% and treatment-related toxicity. Additional endpoints included radiological and clinical response as well as progression-free survival and overall survival from first cycle. Results Sixty-seven cycles were administered (median 4 cycles per patient, mean 6.5 GBq per cycle). Sixty five percent had ≥1 line of prior chemotherapy, 90% abiraterone, enzalutamide or both, and 30% radium-223 radionuclide therapy. All had bone metastases and 35% had visceral metastases. Prostate-specific antigen decline ≥50% was achieved in 50%. Grade 3–4 hematotoxicity was seen in up to 15%. Grade 3–4 non-hematotoxicity was not observed. Eleven patients had restaging scans 3 months post-treatment (5 = partial response, 6 = progressive disease). Fifty-seven percent (4/7) with bone pain had pain improvement. Median progression-free survival was 5.9 months and median overall survival 13.1 months. Patients with prostate-specific antigen decline ≥50% had longer progression-free survival and overall survival. Conclusion 177Lutetium-prostate-specific membrane antigen-I&T therapy is effective with tolerable side effects in our local setting. Prostate-specific antigen decline ≥50% is associated with longer progression-free survival and overall survival.

Efficacy and safety of therapies for advanced prostate cancer in Asia: Evidence from a systematic literature review

“…Forty-seven were removed as duplicates due to overlapping among databases. After screening the titles and abstracts and then the full texts, 27 publications 17 – 43 were shortlisted. No additional studies were identified from the bibliographic search.…”

“… 38 177 Lu-PSMA was administered at a mean dose of approximately 7 GBq or 814 MBq per cycle; patients were administered up to four cycles, with an interval of ⩾6 weeks. 39 – 42 Pembrolizumab 200 mg was administered intravenously every 3 weeks. 43 …”

EpCAM-Targeting Aptamer Radiotracer for Tumor-Specific PET Imaging

“…Therefore, EpCAM has become a tumor-specific biomarker in the context of cancer diagnosis, progression, and targeted treatment. Recently, the 177 Lu radionuclide has attracted wide attention and exhibited great promise for targeted radionuclide therapy (TRT) in clinical use. − Therefore, our aptamer radiotracer platform can potentially be converted to a radioactive therapeutic by replacing 64 Cu with 177 Lu for targeted cancer radiotherapy. Finally, as a synthetic oligonucleotide, aptamers can be chemically conjugated with both imaging reporters and therapeutic agents to form novel theranostics for simultaneous tumor detection and targeted cancer therapy.…”

Is it necessary to do surgical fixation in metastatic bone disease impending pathologic fracture before 177Lu-prostate-specific membrane antigen radionuclide therapy?

“…In a prospective pilot study in 21 Asian populations with advanced prostate cancer taking 177 Lu-PSMA, two patients had pathological hip and humeral fractures. [ 3 ]…”

“…In a prospective pilot study in 21 Asian populations with advanced prostate cancer taking 177 Lu-PSMA, two patients had pathological hip and humeral fractures. [3] The key question is whether it is necessary to fix the bony lesions before Lu-PSMA radionuclide therapy.…”