Efficacy of Antibody Drug Conjugates Alone and in Combination with other Agents in Metastatic Urothelial Carcinoma: A Scoping Review.

Autor:	Grant MJ; Department of Medicine (Section of Medical Oncology), Yale School of Medicine, New Haven, CT, USA.; Yale Cancer Center, Yale School of Medicine, New Haven, CT, USA., Stockhammer P; Department of Medicine, Yale School of Medicine, New Haven, CT, USA., Austin MR; Department of Medicine (Section of Medical Oncology), Yale School of Medicine, New Haven, CT, USA.; Yale Cancer Center, Yale School of Medicine, New Haven, CT, USA., Nemeth Z; Harvey Cushing/John Hay Whitney Medical Library, Yale University, New Haven, CT, USA., Petrylak DP; Department of Medicine (Section of Medical Oncology), Yale School of Medicine, New Haven, CT, USA.; Yale Cancer Center, Yale School of Medicine, New Haven, CT, USA.
Jazyk:	angličtina
Zdroj:	Bladder cancer (Amsterdam, Netherlands) [Bladder Cancer] 2024 Mar 12; Vol. 10 (1), pp. 9-23. Date of Electronic Publication: 2024 Mar 12 (Print Publication: 2024).
DOI:	10.3233/BLC-230070
Abstrakt:	Introduction: Antibody drug conjugates represent a promising class of antineoplastic agents comprised of a monoclonal antibody linked to a potent cytotoxic payload for targeted delivery of chemotherapy to tumors. Various antibody drug conjugates have demonstrated impressive efficacy in patients with metastatic urothelial carcinoma in clinical trials, leading to two FDA approved therapies and several other agents and combinations in clinical development. Materials and Methods: A comprehensive systematic review was undertaken utilizing the principles of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Queried databases included Ovid MEDLINE, Ovid Embase, Web of Science Core Collection and Cochrane CENTRAL Trials. The search sought to identify prospective therapeutic clinical trials in humans with metastatic urothelial carcinoma with a single-arm or randomized controlled trial design investigating antibody drug conjugate-containing regimens. Results: The literature search yielded 4,929 non-duplicated articles, of which 30 manuscripts and conference abstracts were included, which derived from 15 clinical trials including 19 separate cohorts with efficacy outcome results. Eleven trials investigated ADC monotherapy, while two investigated combination regimens, and the remaining two studies were mixed. Five unique ADC targets were represented including Nectin-4, Trop-2, HER2, Tissue Factor, and SLITRK6. Twelve clinical trial cohorts required prior treatment (63%). Objective response rate was reported for all studies and ranged from 27-52% for ADC monotherapies and 34-75% for ADC plus anti-PD-1 agents. Time to event outcome reporting was highly variable. Conclusion: In addition to enfortumab vedotin and sacituzumab govitecan, various HER2-targeted antibody drug conjugates and ADC-anti-PD-1 combination regimens have demonstrated efficacy in clinical trials and are poised for clinical advancement. Competing Interests: Michael J Grant reports honoraria from AstraZeneca and Daiichi Sankyo. Paul Stockhammer, Matthew R. Austin, Zsuzsanna Nameth have no conflicts of interest to report. Daniel P. Petrylak is an Editorial Board member of this journal, but was not involved in the peer-review process nor had access to any information regarding its peer-review. He reports grants or contracts from Ada Cap (Advanced Accelerator Applications), Agensys Inc, Arvinas, Astellas, AstraZeneca, Bayer, BioXcel Therapeutics, Bristol Myers Squibb, Clovis Oncology, Daiichi Sankyo Company Limited, Eisai, Eli Lilly, Endocyte, Ferring, Genentech, Gilead Sciences, Innocrin, MedImmune, Medivation, Merck, Mirati, Novartis, Pfizer, Progenics, Replimune, Roche, Sanofi Aventis, Seattle Genetics; Daniel P. Petrylak also reports consulting fees from Ada Cap (Advanced Accelerator Applications), Amgen, Astellas, AstraZeneca, Bayer, Bicycle Therapeutics, Boehringer Ingelheim, Bristol Myers Squibb, Clovis Oncology, Eli Lilly, Exelixis, Gilead Sciences, Incyte, Infinity Pharmaceuticals, Ipsen, Janssen, Merck & Company Inc, Mirati, Monopteros, Pfizer, Pharmacyclics, Regeneron, Roche, Sanofi Aventis Pharmaceuticals, Seattle Genetics, Urogen. (© 2024 – The authors. Published by IOS Press.)
Databáze:	MEDLINE
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