“…The combination of these two treatments can synergistically eliminate tumor cells. Some scholars believed that ADCs were one of the therapeutic strategies for patients with immunotherapy-resistant and immunologically “cold” tumors [ 175 ]. Fig.…”
With the high incidence of urogenital tumors worldwide, urinary system tumors are among the top 10 most common tumors in men, with prostate cancer ranking first and bladder cancer fourth. Patients with resistant urogenital tumors often have poor prognosis. In recent years, researchers have discovered numerous specific cancer antigens, which has led to the development of several new anti-cancer drugs. Using protein analysis techniques, researchers developed immune checkpoint inhibitors (ICIs) and antibody-conjugated drugs (ADCs) for the treatment of advanced urogenital tumors. However, tumor resistance often leads to the failure of monotherapy. Therefore, clinical trials of the combination of ICIs and ADCs have been carried out in numerous centers around the world. This article reviewed phase 2 and 3 clinical studies of ICIs, ADCs, and their combination in the treatment of urogenital tumors to highlight safe and effective methods for selecting individualized therapeutic strategies for patients. ICIs activate the immune system, whereas ADCs link monoclonal antibodies to toxins, which can achieve a synergistic effect when the two drugs are combined. This synergistic effect provides multiple advantages for the treatment of urogenital tumors.
“…The combination of these two treatments can synergistically eliminate tumor cells. Some scholars believed that ADCs were one of the therapeutic strategies for patients with immunotherapy-resistant and immunologically “cold” tumors [ 175 ]. Fig.…”
With the high incidence of urogenital tumors worldwide, urinary system tumors are among the top 10 most common tumors in men, with prostate cancer ranking first and bladder cancer fourth. Patients with resistant urogenital tumors often have poor prognosis. In recent years, researchers have discovered numerous specific cancer antigens, which has led to the development of several new anti-cancer drugs. Using protein analysis techniques, researchers developed immune checkpoint inhibitors (ICIs) and antibody-conjugated drugs (ADCs) for the treatment of advanced urogenital tumors. However, tumor resistance often leads to the failure of monotherapy. Therefore, clinical trials of the combination of ICIs and ADCs have been carried out in numerous centers around the world. This article reviewed phase 2 and 3 clinical studies of ICIs, ADCs, and their combination in the treatment of urogenital tumors to highlight safe and effective methods for selecting individualized therapeutic strategies for patients. ICIs activate the immune system, whereas ADCs link monoclonal antibodies to toxins, which can achieve a synergistic effect when the two drugs are combined. This synergistic effect provides multiple advantages for the treatment of urogenital tumors.
“…Additional strategies have recently been investigated to expand the group of patients who might benefit from the newer generation of ADCs. Noticeably, new potential targets including proteins expressed by cancer stem cells (CSC), such as PTK7, ephrin-A4, 5T4 and in the TME, such as CD205, CD25, B7-H3, are under investigation with some of these that already reached clinical phases of drug development [ 107 , 108 ]. Bispecific and biparatopic antibodies are also under investigation in preclinical studies.…”
Section: Future Options To Overcome Resistance and Optimise Adc-based...mentioning
In recent years, considerable progress has been made in increasing the knowledge of tumour biology and drug resistance mechanisms in urothelial cancer. Therapeutic strategies have significantly advanced with the introduction of novel approaches such as immune checkpoint inhibitors and Fibroblast Growth Factor Receptor inhibitors. However, despite these novel agents, advanced urothelial cancer is often still progressive in spite of treatment and correlates with a poor prognosis. The introduction of antibody–drug conjugates consisting of a target-specific monoclonal antibody covalently linked to a payload (cytotoxic agent) is a novel and promising therapeutic strategy. In December 2019, the US Food and Drug Administration (FDA) granted accelerated approval to the nectin-4-targeting antibody–drug conjugate, enfortumab vedotin, for the treatment of advanced or metastatic urothelial carcinomas that are refractory to both immune checkpoint inhibitors and platinum-based treatment. Heavily pre-treated urothelial cancer patients reported a significant, 40% response to enfortumab vedotin while other antibody–drug conjugates are currently still under investigation in several clinical trials. We have comprehensively reviewed the available treatment strategies for advanced urothelial carcinoma and outlined the mechanism of action of antibody–drug conjugate agents, their clinical applications, resistance mechanisms and future strategies for urothelial cancer.
“…Metastatic urothelial carcinoma (UC) is a highly lethal disease with a poor prognosis and a 5-year overall survival (OS) of less than 5% [ 1 ]. Urothelial carcinoma of the bladder (UCB) is the most common urinary tract cancer.…”
Background: Pembrolizumab is approved for patients with metastatic urothelial carcinoma (UC) who progressed under platinum therapy. The aim of this study was to assess the efficacy and safety of pembrolizumab in a cohort of real-life UC patients. Methods: This retrospective, observational study included advanced UC patients treated with pembrolizumab in a single institution in France. The co-primary endpoints were overall survival (OS) and progression-free survival (PFS) at 6 months. Secondary endpoints were objective response rate (ORR), duration of response (DOR), disease control rate (DCR) and safety. Results: 78 patients were included in the study. The median OS was 7.3 months (3.8–12.2). The estimated OS rate at 6 months was 61.5% (50.5–72.6). The median PFS was 3.1 months (1.4–7.2). The estimated PFS rate at 6 months was 42.3% (31.1–53.5). The best ORR was 35.9%. The mean DOR was 95.5 days. The DCR was 30.8%. The most common treatment-related adverse events (AEs) of any grade were fatigue (46.2%), diarrhea (11.5%), pruritus (10.3%) and nausea (9.0%). There were no grade 3 AEs that occurred with an incidence of 5% or more. Conclusion: Our results confirmed those of randomized clinical trials concerning the treatment with pembrolizumab in patients with advanced UC that progressed after platinum-based chemotherapy.
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