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

Autor: Telli ML; Stanford University School of Medicine, Stanford, CA, USA., Tolaney SM; Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, USA., Shapiro GI; Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, USA., Middleton M; University of Oxford, Oxford, UK., Lord SR; University of Oxford, Oxford, UK., Arkenau HT; Sarah Cannon Research Institute, HCA Healthcare, London, UK.; University College London, London, UK., Tutt A; Breast Cancer Now Toby Robins Research Centre, The Institute of Cancer Research and Kings College, London, UK.; Guy's and St Thomas' NHS Foundation Trust, London, UK., Abramson V; Vanderbilt University Medical Center, Vanderbilt-Ingram Cancer Center, Nashville, TN, USA., Dean E; The University of Manchester and The Christie NHS Foundation Trust, Manchester, UK.; Oncology R&D, AstraZeneca, Cambridge and Alderley Park, Macclesfield, UK., Haddad TC; Mayo Clinic, Rochester, MN, USA., Wesolowski R; The Ohio State University Comprehensive Cancer Center, Columbus, OH, USA., Ferrer-Playan J; Ares Trading SA, Eysins, Switzerland, an affiliate of Merck KGaA, Darmstadt, Germany., Goddemeier T; the healthcare business of Merck KGaA, Darmstadt, Germany., Grombacher T; the healthcare business of Merck KGaA, Darmstadt, Germany., Dong J; EMD Serono, Billerica, MA, USA., Fleuranceau-Morel P; EMD Serono, Billerica, MA, USA., Diaz-Padilla I; Ares Trading SA, Eysins, Switzerland, an affiliate of Merck KGaA, Darmstadt, Germany.; GlaxoSmithKline, Zug, Switzerland., Plummer R; Newcastle University and Northern Centre for Cancer Care, Newcastle Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK. Ruth.Plummer@newcastle.ac.uk.
Jazyk: angličtina
Zdroj: NPJ breast cancer [NPJ Breast Cancer] 2022 Apr 07; Vol. 8 (1), pp. 45. Date of Electronic Publication: 2022 Apr 07.
DOI: 10.1038/s41523-022-00406-0
Abstrakt: 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/m 2 ; day 1) and berzosertib (140 mg/m 2 ; 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.
(© 2022. The Author(s).)
Databáze: MEDLINE
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