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

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    Authors
    Telli, M. L.
    Tolaney, S. M.
    Shapiro, G. I.
    Middleton, M.
    Lord, S. R.
    Arkenau, H. T.
    Tutt, A.
    Abramson, V.
    Dean, Emma J
    Haddad, T. C.
    Wesolowski, R.
    Ferrer-Playan, J.
    Goddemeier, T.
    Grombacher, T.
    Dong, J.
    Fleuranceau-Morel, P.
    Diaz-Padilla, I.
    Plummer, R.
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    Affiliation
    Stanford University School of Medicine, Stanford, CA, USA
    Issue Date
    2022
    
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    Abstract
    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.
    Citation
    Telli ML, Tolaney SM, Shapiro GI, Middleton M, Lord SR, Arkenau HT, et al. Phase 1b study of berzosertib and cisplatin in patients with advanced triple-negative breast cancer. Vol. 8, npj Breast Cancer. Springer Science and Business Media LLC; 2022.
    Journal
    NPJ Breast Cancer
    URI
    http://hdl.handle.net/10541/625270
    DOI
    10.1038/s41523-022-00406-0
    PubMed ID
    35393425
    Additional Links
    https://dx.doi.org/10.1038/s41523-022-00406-0
    Type
    Article
    Language
    en
    ae974a485f413a2113503eed53cd6c53
    10.1038/s41523-022-00406-0
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