Antibody-Drug Conjugates in Bladder Cancer

Vlachostergios, Panagiotis J.; Jakubowski, Christopher; Niaz, Muhammad Junaid; Lee, Aileen; Thomas, Charlene; Hackett, Amy; Patel, Priyanka; Rashid, Naureen; Tagawa, Scott T.

doi:10.3233/blc-180169

Cited by 31 publications

(22 citation statements)

References 78 publications

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“…The combination of ADCs with immunotherapy attempts to increase patients’ overall response rate. ADCs are monoclonal antibodies conjugated to cytotoxic agents through a chemical linker, which can achieve selective targeting of cancer cells ( 57 ) . In December 2019, the United States Food and Drug Administration (FDA) approved the first ADCs, enfortumab vedotin (EV), for the treatment of platinum-refractory and immune checkpoint blockade-refractory locally advanced or metastatic UC.…”

Section: Immunotherapymentioning

confidence: 99%

Novel Combination Therapies for the Treatment of Bladder Cancer

Peng

Xiao

et al. 2021

Front. Oncol.

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Bladder cancer is the ninth most frequently diagnosed cancer world-wide and ranks 13th in cancer-related deaths. Two tremendous breakthroughs in bladder cancer therapy over the last decades are the approval of immune checkpoint inhibitors(ICIs)and the fibroblast growth factor receptor tyrosine kinase inhibitor (FGFR-TKI) erdafitinib for treating this deadly disease. Despite the beneficial effects of these approaches, the low response rate and the potential resistance of the cancer are major concerns. Hence, novel combination therapies to overcome these limitations have been investigated. In this context, combining immunotherapy with targeted drugs is an appealing therapeutic option to improve response and reduce the emergence of resistance in the management of bladder cancer. In this review, the rationale of using different therapeutic combinations is discussed according to the mechanistic differences, emphasizing the efficacy and safety based on evidence collected from preclinical and clinical studies. Finally, we highlight the limitations of these combinations and provide suggestions for further efforts in this challenging field.

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Section: Immunotherapymentioning

confidence: 99%

Novel Combination Therapies for the Treatment of Bladder Cancer

Peng

Xiao

et al. 2021

Front. Oncol.

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“…An anti-CD125 ADC has potent cytotoxicity against MIBC cells [ 99 ]. Additional target with accompanying ADCs that have shown promise in preclinical models of bladder cancer include The Slit- and Trk-like receptor family, transmembrane glycoprotein epithelial cell-adhesion molecule, and Thomsen-Fridenreich antigen and are described in further detail in [ 100 ].…”

Section: Futurementioning

confidence: 99%

Targeted Molecular Therapeutics for Bladder Cancer—A New Option beyond the Mixed Fortunes of Immune Checkpoint Inhibitors?

Bednova

Leyton

2020

IJMS

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The fact that there are now five immune checkpoint inhibitor (ICI) monoclonal antibodies approved since 2016 that target programmed cell death protein 1 or programmed death ligand-1 for the treatment of metastatic and refractory bladder cancer is an outstanding achievement. Although patients can display pronounced responses that extend survival when treated with ICIs, the main benefit of these drugs compared to traditional chemotherapy is that they are better tolerated and result in reduced adverse events (AEs). Unfortunately, response rates to ICI treatment are relatively low and, these drugs are expensive and have a high economic burden. As a result, their clinical efficacy/cost-value relationship is debated. Long sought after targeted molecular therapeutics have now emerged and are boasting impressive response rates in heavily pre-treated, including ICI treated, patients with metastatic bladder cancer. The antibody-drug conjugates (ADCs) enfortumab vedotin (EV) and sacituzumab govitecan (SG) have demonstrated the ability to provide objective response rates (ORRs) of 44% and 31% in patients with bladder tumor cells that express Nectin-4 and Trop-2, respectively. As a result, EV was approved by the U.S. Food and Drug Administration for the treatment of patients with advanced or metastatic bladder cancer who have previously received ICI and platinum-containing chemotherapy. SG has been granted fast track designation. The small molecule Erdafitinib was recently approved for the treatment of patients with advanced or metastatic bladder cancer with genetic alterations in fibroblast growth factor receptors that have previously been treated with a platinum-containing chemotherapy. Erdafitinib achieved an ORR of 40% in patients including a proportion who had previously received ICI therapy. In addition, these targeted drugs are sufficiently tolerated or AEs can be appropriately managed. Hence, the early performance in clinical effectiveness of these targeted drugs are substantially increased relative to ICIs. In this article, the most up to date follow-ups on treatment efficacy and AEs of the ICIs and targeted therapeutics are described. In addition, drug price and cost-effectiveness are described. For best overall value taking into account clinical effectiveness, price and cost-effectiveness, results favor avelumab and atezolizumab for ICIs. Although therapeutically promising, it is too early to determine if the described targeted therapeutics provide the best overall value as cost-effectiveness analyses have yet to be performed and long-term follow-ups are needed. Nonetheless, with the arrival of targeted molecular therapeutics and their increased effectiveness relative to ICIs, creates a potential novel paradigm based on ‘targeting’ for affecting clinical practice for metastatic bladder cancer treatment.

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“…[19][20][21] However, response to treatment is 20%. [22] Breast cancer is the most common cancer in women worldwide. [23] Treatment rate is increasing day by day in breast cancers diagnosed early.…”

Section: Treatment Areas Of Sacituzumab Govitecanmentioning

confidence: 99%

Sacituzumab Govitecan and Treatment Area

Ün

Coşkun

2020

JEB Med Sci

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Although there are diagnosis and treatment methods for cancer, treatment methods for metastatic cancers are limited. Therefore, new treatments for metastatic cancer are being investigated. Antibody drug conjugates (ADCs) are a new group of drugs that enable highly toxic drugs to be targeted. Sacituzumab govitecan is a second-generation antibody drug conjugate that is promising with its results in many cancer treatment trials.

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Antibody-Drug Conjugates in Bladder Cancer

Cited by 31 publications

References 78 publications

Novel Combination Therapies for the Treatment of Bladder Cancer

Novel Combination Therapies for the Treatment of Bladder Cancer

Targeted Molecular Therapeutics for Bladder Cancer—A New Option beyond the Mixed Fortunes of Immune Checkpoint Inhibitors?

Sacituzumab Govitecan and Treatment Area

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