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Review
. 2020 Jul;20(7):551-561.
doi: 10.1080/14737140.2020.1782201. Epub 2020 Jul 21.

The emerging role of antibody-drug conjugates in urothelial carcinoma

Michael Lattanzi  1 , Jonathan E Rosenberg  1   2
Affiliations
Review

The emerging role of antibody-drug conjugates in urothelial carcinoma

Michael Lattanzi et al. Expert Rev Anticancer Ther. 2020 Jul.

Abstract

Introduction: In December 2019, the US Food and Drug Administration granted accelerated approval to the novel nectin-4-targeting antibody-drug conjugate, enfortumab vedotin, for the treatment of platinum-refractory and immune checkpoint blockade-refractory locally advanced or metastatic urothelial carcinoma. Antibody-drug conjugates represent a new therapeutic modality in urothelial cancer; and beyond nectin-4, agents targeting Trop-2, HER2, and EpCAM are also in clinical development.

Areas covered: This review outlines the biologic rationale and the clinical development of novel antibody-drug conjugates for the treatment of urothelial cancer across the spectrum of disease from non-muscle-invasive bladder cancer through treatment-refractory metastatic disease.

Expert opinion: The high response rates observed with enfortumab vedotin - both as monotherapy and in combination with checkpoint blockade immunotherapy - suggest this and other antibody-drug conjugates may have efficacy similar to or even exceeding that of traditional cytotoxic chemotherapy. Ongoing clinical development of antibody-drug conjugates in urothelial cancer will address the optimal combination or sequencing strategy with anti-PD-1/L1 immunotherapy and platinum-based chemotherapy.

Keywords: Antibody-drug conjugate; HER2; bladder cancer; enfortumab vedotin; immunotherapy; nectin-4; pembrolizumab; sacituzumab govitecan; urothelial.

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Highlighted References

    1. Rosenberg JE, O’Donnell PH, Balar AV, McGregor BA, Heath EI, Yu EY, et al. Pivotal Trial of Enfortumab Vedotin in Urothelial Carcinoma After Platinum and Anti-Programmed Death 1/Programmed Death Ligand 1 Therapy. J Clin Oncol. 2019;37(29):2592–600.

      ** Registrational phase II study of EV in platinum-refractory and checkpoint blockade-refractory mUC

    1. Rosenberg J. Study EV-103: Preliminary durability results of enfortumab vedotin plus pembrolizumab for locally advanced or metastatic urothelial carcinoma. . ASCO Genitourinary Cancers Symposium; February 20; San Francisco, CA: American Society of Clinical Oncology; 2020.

      **Most recently updated preliminary data from the phase Ib trial of of EV plus pembrolizumab for cisplatin-ineligible patients with mUC

    1. Tagawa ST, Balar A, Petrylak DP, Grivas P, Agarwal N, Sternberg CN, et al. Initial results from TROPHY-U-01: A phase II open-label study of sacituzumab govitecan in patients (Pts) with metastatic urothelial cancer (mUC) after failure of platinum-based regimens (PLT) or immunotherapy. Ann Oncol. 2019;30:890-+.

      *Updated preliminary results from the phase II study of Trop-2 ADC sacituzumab govitecan in platinum-refractory and checkpoint blockade-refractory mUC

    1. Sheng XN, Zhou AP, Yao X, Shi YX, Luo H, Shi BK, et al. A phase II study of RC48-ADC in HER2-positive patients with locally advanced or metastatic urothelial carcinoma. Journal of Clinical Oncology. 2019;37(15).

      *Phase II study of the HER2-targeted ADC RC48 in HER2+ mUC

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