Current and emerging role of sacituzumab govitecan in the management of urothelial carcinoma

Thomas, Vinay Mathew; Tripathi, Nishita; Agarwal, Neeraj; Swami, Umang

doi:10.1080/14737140.2022.2049763

Cited by 10 publications

(10 citation statements)

References 23 publications

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“…However, although ADCs exhibit less toxicity and greater therapeutic activity, latent side effects, including rash, neutral granulocytopenia, hematotoxicity, and neurological disorders, have been reported in clinical trials. 114,137 Thus, these drawbacks must be overcome to develop next-generation drug candidates. Early evidence suggests that resistance to ADCs involves different signaling pathways, including the loss of payload efficiency, alteration of ADCs processing and internalization, and blockade of antibody attachment.…”

Section: Discussionmentioning

confidence: 99%

“…EV and SG have been approved for clinical applications, and many other ADCs are being assessed in both, preclinical and clinical studies. However, although ADCs exhibit less toxicity and greater therapeutic activity, latent side effects, including rash, neutral granulocytopenia, hematotoxicity, and neurological disorders, have been reported in clinical trials 114,137 . Thus, these drawbacks must be overcome to develop next‐generation drug candidates.…”

Section: Discussionmentioning

confidence: 99%

“…SG (IMMU‐132) was designed to contain an anti‐Trop‐2 mAb linked to an active metabolite of irinotecan, SN‐38, through a hydrolyzable linker 136 . After the phase I/II basket trial IMMU‐132‐01 (NCT01631552) demonstrated encouraging results in the phase I dose‐finding part, an open‐label, multicohort, phase II registration trial, TROPHY‐U‐01 (IMMU‐132‐06; NCT03547973), was developed to assess the influence of SG in patients with local, unresectable, or metastatic advanced UC who had progression after previous chemotherapy and platinum‐based ICI 137 . An ORR of 27.4% (31out of 113) was observed after a median follow‐up period of 9.1 months.…”

Section: Characteristics Of Adcsmentioning

confidence: 99%

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Targeted therapies in bladder cancer: signaling pathways, applications, and challenges

Peng,

Chu,

Peng

et al. 2023

MedComm

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Bladder cancer (BC) is one of the most prevalent malignancies in men. Understanding molecular characteristics via studying signaling pathways has made tremendous breakthroughs in BC therapies. Thus, targeted therapies including immune checkpoint inhibitors (ICIs), antibody–drug conjugates (ADCs), and tyrosine kinase inhibitor (TKI) have markedly improved advanced BC outcomes over the last few years. However, the considerable patients still progress after a period of treatment with current therapeutic regimens. Therefore, it is crucial to guide future drug development to improve BC survival, based on the molecular characteristics of BC and clinical outcomes of existing drugs. In this perspective, we summarize the applications and benefits of these targeted drugs and highlight our understanding of mechanisms of low response rates and immune escape of ICIs, ADCs toxicity, and TKI resistance. We also discuss potential solutions to these problems. In addition, we underscore the future drug development of targeting metabolic reprogramming and cancer stem cells (CSCs) with a deep understanding of their signaling pathways features. We expect that finding biomarkers, developing novo drugs and designing clinical trials with precisely selected patients and rationalized drugs will dramatically improve the quality of life and survival of patients with advanced BC.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Characteristics Of Adcsmentioning

confidence: 99%

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Targeted therapies in bladder cancer: signaling pathways, applications, and challenges

Peng,

Chu,

Peng

et al. 2023

MedComm

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“…24 The drug has also received accelerated approval for locally advanced or metastatic urothelial cancer in patients previously treated with platinum-based chemotherapy and a programmed cell death receptor-1 (PD-1) or programmed death-ligand 1 (PD-L1) inhibitor. 25 However, the clinical use of sacituzumab govitecan is limited due to its adverse effects. Common side effects include diarrhea, nausea, fatigue, alopecia, and neutropenia.…”

Section: Sacituzumab Govitecanmentioning

confidence: 99%

Current and Emerging Treatments for Urothelial Carcinoma: A Focus on Enfortumab Vedotin

Shafique¹,

Haseeb²,

Siddiq³

et al. 2023

CMAR

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Urothelial carcinoma is a common malignancy that affects the urinary system, with bladder cancer being the most prevalent form. Although the management of early-stage disease has seen significant improvements, the treatment of locally advanced and metastatic urothelial carcinoma remains challenging. Over the past decade, there has been an explosion in the number of therapies available for the treatment of advanced disease, with immune checkpoint inhibitors and antibody-drug conjugates leading the way. Enfortumab vedotin is an antibody-drug conjugate that targets Nectin-4, a protein that is overexpressed in urothelial carcinoma cells. In clinical trials, it has shown promising outcomes for the treatment of advanced urothelial carcinoma that has progressed after chemotherapy or immunotherapy. The US Food and Drug Administration has granted expedited approval for enfortumab vedotin in the treatment of advanced urothelial carcinoma. This review provides an overview of the current and emerging treatments for urothelial carcinoma, with a particular focus on enfortumab vedotin. We discuss the mechanisms of action, clinical efficacy, safety, and ongoing research of enfortumab vedotin, along with the current landscape of other approved therapies and promising agents in development. The aim of this review is to provide a comprehensive and upto-date summary of the available treatment options for urothelial carcinoma, including their limitations and future prospects.

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“…A phase II study (TROPHY-U-01) has shown the benefits of this drug. ORR was 27.4% (95% CI: 19.6–36.9), median DOR was 7.2 months (95% CI: 4.7–8.6), median PFS was 5.4 months (95% CI: 3.5–7.2), and OS was 10.9 months (95% CI: 9.0–13.8) [ 193 , 194 , 195 ].…”

Section: Treatment Of Cn+ Patientsmentioning

confidence: 99%

Management of Bladder Cancer Patients with Clinical Evidence of Lymph Node Invasion (cN+)

Małkiewicz

Gurwin

Karwacki

et al. 2022

Cancers

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The purpose of this review is to present the current knowledge about the diagnostic and treatment options for bladder cancer (BCa) patients with clinically positive lymph nodes (cN+). This review shows compaction of CT and MRI performance in preoperative prediction of lymph node invasion (LNI) in BCa patients, along with other diagnostic methods. Most scientific societies do not distinguish cN+ patients in their guidelines; recommendations concern muscle-invasive bladder cancer (MIBC) and differ between associations. The curative treatment that provides the best long-term survival in cN+ patients is a multimodal approach, with a combination of neoadjuvant chemotherapy (NAC) and radical cystectomy (RC) with extended pelvic lymph node dissection (ePLND). The role of adjuvant chemotherapy (AC) remains uncertain; however, emerging evidence indicates comparable outcomes to NAC. Therefore, in cN+ patients who have not received NAC, AC should be implemented. The response to ChT is a crucial prognostic factor for cN+ patients. Recent studies demonstrated the growing importance of immunotherapy, especially in ChT-ineligible patients. Moreover, immunotherapy can be suitable as adjuvant therapy in selected cases. In cN+ patients, the extended template of PLND should be utilized, with the total resected node count being less important than the template. This review is intended to draw special attention to cN+ BCa patients, as the oncological outcomes are significantly worse for this group.

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Current and emerging role of sacituzumab govitecan in the management of urothelial carcinoma

Cited by 10 publications

References 23 publications

Targeted therapies in bladder cancer: signaling pathways, applications, and challenges

Targeted therapies in bladder cancer: signaling pathways, applications, and challenges

Current and Emerging Treatments for Urothelial Carcinoma: A Focus on Enfortumab Vedotin

Management of Bladder Cancer Patients with Clinical Evidence of Lymph Node Invasion (cN+)

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