Antibody–Drug Conjugates in Uro-Oncology

Sigorski, Dawid; Różanowski, Paweł; Iżycka-Świeszewska, Ewa; Wiktorska, Katarzyna

doi:10.1007/s11523-022-00872-3

Cited by 3 publications

(3 citation statements)

References 131 publications

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“…Of all urogenital carcinomas, ADC showed the best efficacy profile in CU. The targets of the pharmacological action of EV and SG are respectively Nectin-4 and Trop-2 [ 46 ].…”

Section: Antibody-drug Conjugatesmentioning

confidence: 99%

Precision Medicine in the Treatment of Locally Advanced or Metastatic Urothelial Cancer: New Molecular Targets and Pharmacological Therapies

Vitiello

Ferrara²,

Lasala

et al. 2022

Cancers

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Many variants of urothelial cancer present diagnostic challenges and carry clinical implications that influence prognosis and treatment decisions. The critical issues of treatment-resistant clones are a crucial barrier to care in individuals affected by urothelial carcinoma. Laying the foundations for the resistance evolution, a wide mutational heterogeneity characterizes urothelial carcinoma, noticeable also in patients affected by a early stage disease. In recent years the growing knowledge of the pathogenesis and molecular paths underlying the onset and progression of urothelial cancer are leading to the development of new therapies based on immune checkpoints. Chemotherapy and immunotherapy both operate selectively by shaping the developmental trajectory of urothelial carcinoma in the course of the illness. To date, a promising new therapeutic treatment is represented by antibody-drug conjugates, therapeutic tools that exploit the targeted ability of an antibody to administer cytotoxic drugs directly to the tumor. Indeed, nowadays in the clinical setting there are several treatments available for the treatment of locally advanced or metastatic urothelial cancer, from classic chemotherapeutics such as Gemcitabine, Cisplatin and Carboplatin, Paclitaxel and Docetaxel, to Programmed cell death protein 1 (PD-1) or Programmed death-ligand 1 (PD-L1) inhibitors such as Atezolizumab, Avelumab, Nivolumab, Pembrolizumab, up to anti-nectin 4 Enfortumab Vedotin and Sacituzumab govitecan, which binds Tumor-associated calcium signal transducer 2 (Trop-2) and activates as a topoisomerase inhibitor. The aim of this work is to describe the molecular mechanisms underlying the onset of the urothelial cancer and provide an overview of the immunotherapies that can be used in the clinical setting to counteract it, deepening the efficacy and safety results of the pivotal studies and the place in therapy of these treatments.

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“…Of all urogenital carcinomas, ADC showed the best efficacy profile in CU. The targets of the pharmacological action of EV and SG are respectively Nectin-4 and Trop-2 [ 46 ].…”

Section: Antibody-drug Conjugatesmentioning

confidence: 99%

Precision Medicine in the Treatment of Locally Advanced or Metastatic Urothelial Cancer: New Molecular Targets and Pharmacological Therapies

Vitiello

Ferrara²,

Lasala

et al. 2022

Cancers

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“…Data have established that ADCs as anticancer therapeutics have a unique mechanism of action, which includes the targeted delivery and release of its payload at the tumor site through MoAb antibody components, thus exerting simultaneous roles as both targeted therapy and chemotherapy. 2,5 Since 2000, several ADCs used as anticancer drugs have been approved by the US Food and Drug Administration. Some include gemtuzumab ozogamicin (Mylotarg; Pfizer Inc.), brentuximab vedotin (Adcetris; Seattle Genetics), inotuzumab ozogamicin (Besponsa; Pfizer Inc.), polatuzumab vedotin (Polivy; Genentech), trastuzumab emtansine (T-DM1, Kadcyla; Genentech), trastuzumab deruxtecan (T-DXd, Enhertu; Daiichi Sankyo Company Ltd.), sacituzumab govitecan (Trodelvy; Gilead), enfortumab vedotin (Padcev; Astellas Pharma US, Inc., and Seagen Inc.), and tisotoumab vedotin (Tivdak; Seagen Inc. Genmab).…”

Section: Introductionmentioning

confidence: 99%

“…The clinical efficacy and toxicity of ADCs are affected by each component. Data have established that ADCs as anticancer therapeutics have a unique mechanism of action, which includes the targeted delivery and release of its payload at the tumor site through MoAb antibody components, thus exerting simultaneous roles as both targeted therapy and chemotherapy 2,5 …”

Section: Introductionmentioning

confidence: 99%

Treatment‐related adverse events of antibody–drug conjugates in clinical trials: A systematic review and meta‐analysis

Ying

Liu

Wang

et al. 2022

Cancer

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Background Antibody–drug conjugates (ADCs) have complex molecular structures and have been tested in numerous clinical trials. Therefore, understanding the mechanisms of their toxicity when applied in medical practice is of high importance. Methods In a systematic review and meta‐analysis of data gathered from different scientific databases (PubMed, Embase, Cochrane, and Web of Science) between January 1, 2000, and June 7, 2022, the authors applied a random‐effects model with logit transformation and evaluated the heterogeneity between studies using I2 statistics. The primary outcome was the incidence and 95% confidence interval (CI) for all‐grade and grade ≥3 treatment‐related adverse events and differences between different drugs, molecular structures, and cancer types. Results In total, 2511 records were identified that included 169 clinical trials involving 22,492 patients. The overall incidence of treatment‐related adverse events was 91.2% (95% CI, 90.7%–91.7%; I2 = 95.9%) for all‐grade adverse events and 46.1% (95% CI, 45.2%–47.0%; I2 = 96.3%) for grade ≥3 adverse events. The most common all‐grade adverse events were lymphopenia (53.0%; 95% CI, 48.7%–57.3%), nausea (44.1%; 95% CI, 43.2%–44.9%), neutropenia (43.7%; 95% CI, 42.6%–44.9%), blurred vision (40.5%; 95% CI, 37.4%–43.6%), and peripheral neuropathy (39.6%; 95% CI, 38.2%–41.1%); and the most common grade ≥3 adverse events were neutropenia (31.2%; 95% CI, 30.2%–32.3%), hypoesthesia (23.3%; 95% CI, 10.6%–35.9%), thrombocytopenia (22.6%; 95% CI, 21.3%–23.9%), febrile neutropenia (21.2%; 95% CI, 19.3%–23.1%), and lymphopenia (21.0%; 95% CI, 18.2%–23.7%). Conclusions Different ADCs appear to affect various treatment‐related adverse events and provide comprehensive data on treatment‐related adverse events for ADCs. The current results provide an important reference for clinicians and patients on how to care for toxicities from ADCs in clinical practice. Lay summary Unique anticancer drugs called antibody–drug conjugates (ADCs) have made significant progress in oncology in recent years because of their great success, and they are rapidly being used in the clinic as well as in hundreds of ongoing trials exploring their further use. The occurrence of serious side effects (adverse events) related to the receipt of ADCs was studied using data from 169 clinical trials involving 22,492 patients to determine the treatment‐related causes of higher toxicity and adverse events in patients who receive ADCs, because these data are crucial for informing physicians how to safely treat patients using ADCs. The results indicate that different ADCs appear to affect various adverse events related to their use, providing comprehensive data on these ADCs that provide an important reference for clinicians and patients on how to care for toxicities from ADCs in clinical practice.

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Durable Response to Enfortumab Vedotin Compared to Re-challenging Chemotherapy in Metastatic Urothelial Carcinoma After Checkpoint Inhibitors

Uchimoto,

Tsuchida,

Komura

et al. 2024

Targ Oncol

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Antibody–Drug Conjugates in Uro-Oncology

Cited by 3 publications

References 131 publications

Precision Medicine in the Treatment of Locally Advanced or Metastatic Urothelial Cancer: New Molecular Targets and Pharmacological Therapies

Precision Medicine in the Treatment of Locally Advanced or Metastatic Urothelial Cancer: New Molecular Targets and Pharmacological Therapies

Treatment‐related adverse events of antibody–drug conjugates in clinical trials: A systematic review and meta‐analysis

Durable Response to Enfortumab Vedotin Compared to Re-challenging Chemotherapy in Metastatic Urothelial Carcinoma After Checkpoint Inhibitors

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