000			04520nam a22006017a 4500
008			240723s20242024 xxu||||| |||| 00| 0 eng d
022			_a2041-1723
024			_a10.1038/s41467-024-46961-x [pii]
024			_aPMC10973408 [pmc]
040			_aOvid MEDLINE(R)
099			_a38538574
245			_aAdjuvant nivolumab, capecitabine or the combination in patients with residual triple-negative breast cancer: the OXEL randomized phase II study.
251			_aNature communications . 15(1):2691, 2024 Mar 27.
252			_aNat Commun. 15(1):2691, 2024 Mar 27.
253			_aNature communications
260			_c2024
260			_p2024 Mar 27
260			_fFY2024
265			_sepublish
265			_tMEDLINE
520			_aChemotherapy and immune checkpoint inhibitors have a role in the post-neoadjuvant setting in patients with triple-negative breast cancer (TNBC). However, the effects of nivolumab, a checkpoint inhibitor, capecitabine, or the combination in changing peripheral immunoscore (PIS) remains unclear. This open-label randomized phase II OXEL study (NCT03487666) aimed to assess the immunologic effects of nivolumab, capecitabine, or the combination in terms of the change in PIS (primary endpoint). Secondary endpoints included the presence of ctDNA, toxicity, clinical outcomes at 2-years and association of ctDNA and PIS with clinical outcomes. Forty-five women with TNBC and residual invasive disease after standard neoadjuvant chemotherapy were randomized to nivolumab, capecitabine, or the combination. Here we show that a combination of nivolumab plus capecitabine leads to a greater increase in PIS from baseline to week 6 (91%) compared with nivolumab (47%) or capecitabine (53%) alone (log-rank p = 0.08), meeting the pre-specified primary endpoint. In addition, the presence of circulating tumor DNA (ctDNA) is associated with disease recurrence, with no new safety signals in the combination arm. Our results provide efficacy and safety data on this combination in TNBC and support further development of PIS and ctDNA analyses to identify patients at high risk of recurrence. Copyright © 2024. The Author(s).
546			_aEnglish
650			_a*Nivolumab
650			_a*Triple Negative Breast Neoplasms
650			_aAntineoplastic Combined Chemotherapy Protocols/ae [Adverse Effects]
650			_aCapecitabine/ae [Adverse Effects]
650			_aFemale
650			_aHumans
650			_aNeoadjuvant Therapy
650			_aNeoplasm Recurrence, Local/pa [Pathology]
650			_aNivolumab/tu [Therapeutic Use]
650			_aTriple Negative Breast Neoplasms/dt [Drug Therapy]
650			_aTriple Negative Breast Neoplasms/pa [Pathology]
650			_zAutomated
651			_aWashington Cancer Institute
656			_aAssociate Dean for Research Development
656			_aMedStar Health
657			_aClinical Trial, Phase II
657			_aJournal Article
657			_aRandomized Controlled Trial
700			_aChitalia, Ami _bWCI
700			_aGallagher, Christopher _bWCI
700			_aSchlam, Ilana _bWCI
700			_aSwain, Sandra M _bMSH
700			_aTiwari, Shruti _bMWHC
790			_aLynce F, Mainor C, Donahue RN, Geng X, Jones G, Schlam I, Wang H, Toney NJ, Jochems C, Schlom J, Zeck J, Gallagher C, Nanda R, Graham D, Stringer-Reasor EM, Denduluri N, Collins J, Chitalia A, Tiwari S, Nunes R, Kaltman R, Khoury K, Gatti-Mays M, Tarantino P, Tolaney SM, Swain SM, Pohlmann P, Parsons HA, Isaacs C
856			_uhttps://dx.doi.org/10.1038/s41467-024-46961-x _zhttps://dx.doi.org/10.1038/s41467-024-46961-x
858			_yChitalia, Ami _uhttp://orcid.org/0009-0001-0274-2150 _zhttp://orcid.org/0009-0001-0274-2150 _zhttp://orcid.org/0000-0002-3846-5052 _zhttp://orcid.org/0000-0003-4996-0400 _zhttp://orcid.org/0000-0002-1320-3830
858			_yGallagher, Christopher _uhttp://orcid.org/0000-0002-3846-5052 _zhttp://orcid.org/0009-0001-0274-2150 _zhttp://orcid.org/0000-0002-3846-5052 _zhttp://orcid.org/0000-0003-4996-0400 _zhttp://orcid.org/0000-0002-1320-3830
858			_ySchlam, Ilana _uhttp://orcid.org/0000-0003-4996-0400 _zhttp://orcid.org/0009-0001-0274-2150 _zhttp://orcid.org/0000-0002-3846-5052 _zhttp://orcid.org/0000-0003-4996-0400 _zhttp://orcid.org/0000-0002-1320-3830
858			_ySwain, Sandra M _uhttp://orcid.org/0000-0002-1320-3830 _zhttp://orcid.org/0009-0001-0274-2150 _zhttp://orcid.org/0000-0002-3846-5052 _zhttp://orcid.org/0000-0003-4996-0400 _zhttp://orcid.org/0000-0002-1320-3830
942			_cART _dArticle
999			_c14317 _d14317