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Phase 1b study of berzosertib and cisplatin in patients with advanced triple-negative breast cancer

Lookup NU author(s): Professor Ruth Plummer

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Abstract

© 2022, The Author(s). Platinum derivatives are commonly used for the treatment of patients with metastatic triple-negative breast cancer (TNBC). However, resistance often develops, leading to treatment failure. This expansion cohort (part C2) of the previously reported phase 1b trial (NCT02157792) is based on the recommended phase 2 dose of the combination of the ataxia-telangiectasia and Rad3-related (ATR) inhibitor berzosertib and cisplatin observed in patients with advanced solid tumors, including TNBC. Forty-seven patients aged ≥18 years with advanced TNBC received cisplatin (75 mg/m2; day 1) and berzosertib (140 mg/m2; days 2 and 9), in 21-day cycles. Berzosertib was well tolerated, with a similar toxicity profile to that reported previously for this combination. The overall response rate (90% confidence interval) was 23.4% (13.7, 35.8). No relevant associations were observed between response and gene alterations. Further studies combining ATR inhibitors with platinum compounds may be warranted in highly selected patient populations.

Publication metadata

Author(s): Telli ML, Tolaney SM, Shapiro GI, Middleton M, Lord SR, Arkenau HT, Tutt A, Abramson V, Dean E, Haddad TC, Wesolowski R, Ferrer-Playan J, Goddemeier T, Grombacher T, Dong J, Fleuranceau-Morel P, Diaz-Padilla I, Plummer R

Publication type: Article

Publication status: Published

Journal: n p j Breast Cancer

Year: 2022

Volume: 8

Issue: 1

Online publication date: 07/04/2022

Acceptance date: 16/02/2022

Date deposited: 27/04/2022

ISSN (electronic): 2374-4677

Publisher: Nature Publishing Group

URL: https://doi.org/10.1038/s41523-022-00406-0

DOI: 10.1038/s41523-022-00406-0

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