Antibody-Drug Conjugates in Prostate Cancer: A Systematic Review

Abstract

The prognosis in the setting of metastatic castration-resistant prostate cancer patients (mCRPC) remains limited. Therefore, novel treatment strategies remain an unmet need. Antibody-drug conjugates (ADC) emerged as a new drug concept with the potential to deliver a cytotoxic payload with limited off-target toxicity and potentially bystander effect. Following the success of ADCs in breast cancer and urothelial tumours, their activity in prostate cancer is now under investigation. Thus, the aim of this systematic review was to identify published and ongoing prospective clinical trials regarding ADC treatment in prostate cancer.A systematic search of PubMed, MEDLINE, and Web of Science was conducted as per PRISMA guidelines to identify prospective clinical trials of ADC in prostate cancer. Trials are currently ongoing on ClinicalTrials.gov and in the EU. The Clinical Trials Register was also identified. Abstracts, publications in languages other than English, review articles, retrospective analyses, and phase I trials were excluded.A total of six phase I/II prospective clinical trials already published were included. Seven ongoing trials were also identified. All studies were in the refractory/advanced tumour setting, and two included only mCRPC patients. The ADC targets were prostate-specific membrane antigen (PSMA), trophoblast cell surface antigen-2 (TROP-2), six-transmembrane epithelial antigen of prostate-1 (STEAP-1), tissue factor (TF), deltalike protein 3 (DLL-3), B7-H3 family of proteins (B7-H3), and human epidermal growth factor receptor 2 (HER2). Regarding the efficacy of PSMA ADC treatment in the second-line or beyond mCRPC setting, a PSA ≥ 50% decline rate in 14% of all treated patients was reported. One patient achieved a complete response with TROP-2 ADC. Overall, a wide range of safety issues were raised, particularly in connection with neuropathy and hematologic toxicity.Novel therapies have been changing the scope of treatment in mCRPC. ADCs seem to provide efficacy benefits, even with potential toxicity. The results of most prospective ongoing studies are still awaited, and a longer follow-up time is warranted to evaluate the real impact of ADCs in PCa.

Circulating tumor cell characterization and classification by novel combinatorial dual-color (CoDuCo) in situ hybridization and supervised machine learning

“…Similarly, the increased multiplex capacity of the CoDuCo approach enabled us to include PSMA as additional prostate-specific marker. Novel PSMA-targeting drugs, such as the radioligand agent Lutetium-177 PSMA-617 (trade name: Pluvicto) (18), are now available, and others are under investigation (17, 57). Predictive biomarkers are urgently needed, as the expression of PSMA is highly heterogeneous and dynamic (58).…”

Assessment of Cell Surface Targets in Metastatic Prostate Cancer: Expression Landscape and Molecular Correlates

“…Of the constantly expanding spectrum of cell-surface targets in oncology, delta-like ligand 3 (DLL3), carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5), and trophoblast cell-surface antigen 2 (TROP2) have been a focus for pre-clinical and clinical drug development efforts for advanced PC [23][24][25][26][27][28] .…”