Adjuvant nivolumab, capecitabine or the combination in patients with residual triple-negative breast cancer: the OXEL randomized phase II study.


Journal

Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555

Informations de publication

Date de publication:
27 Mar 2024
Historique:
received: 05 01 2023
accepted: 15 03 2024
medline: 28 3 2024
pubmed: 28 3 2024
entrez: 28 3 2024
Statut: epublish

Résumé

Chemotherapy 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.

Identifiants

pubmed: 38538574
doi: 10.1038/s41467-024-46961-x
pii: 10.1038/s41467-024-46961-x
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

2691

Informations de copyright

© 2024. The Author(s).

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Auteurs

Filipa Lynce (F)

Division of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA. Filipa_Lynce@dfci.harvard.edu.
Breast Oncology Program, Dana-Farber Brigham Cancer Center, Boston, MA, USA. Filipa_Lynce@dfci.harvard.edu.
Harvard Medical School, Boston, MA, USA. Filipa_Lynce@dfci.harvard.edu.

Candace Mainor (C)

MedStar Georgetown University Hospital, Washington, DC, USA.

Renee N Donahue (RN)

Center for Immuno-Oncology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.

Xue Geng (X)

Georgetown University, Washington, DC, USA.

Greg Jones (G)

NeoGenomics, Durham, NC, USA.

Ilana Schlam (I)

MedStar Washington Hospital Center, Washington, DC, USA.
Tufts Medical Center, Boston, MA, USA.

Hongkun Wang (H)

Georgetown University, Washington, DC, USA.

Nicole J Toney (NJ)

Center for Immuno-Oncology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.

Caroline Jochems (C)

Center for Immuno-Oncology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.

Jeffrey Schlom (J)

Center for Immuno-Oncology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.

Jay Zeck (J)

MedStar Georgetown University Hospital, Washington, DC, USA.

Christopher Gallagher (C)

MedStar Washington Hospital Center, Washington, DC, USA.

Rita Nanda (R)

University of Chicago, Chicago, IL, USA.

Deena Graham (D)

Hackensack University Medical Center, Hackensack, NJ, USA.

Erica M Stringer-Reasor (EM)

University of Alabama at Birmingham, Birmingham, AL, USA.

Neelima Denduluri (N)

AstraZeneca, Arlington, VA, USA.

Julie Collins (J)

MedStar Georgetown University Hospital, Washington, DC, USA.
AstraZeneca, Arlington, VA, USA.

Ami Chitalia (A)

MedStar Washington Hospital Center, Washington, DC, USA.

Shruti Tiwari (S)

MedStar Washington Hospital Center, Washington, DC, USA.

Raquel Nunes (R)

Johns Hopkins Sidney Kimmel Cancer Center, Baltimore, MD, USA.
AstraZeneca, Arlington, VA, USA.

Rebecca Kaltman (R)

Inova, Fairfax, VA, USA.

Katia Khoury (K)

University of Alabama at Birmingham, Birmingham, AL, USA.

Margaret Gatti-Mays (M)

The Ohio State University, Columbus, OH, USA.

Paolo Tarantino (P)

Division of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Harvard Medical School, Boston, MA, USA.

Sara M Tolaney (SM)

Division of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Breast Oncology Program, Dana-Farber Brigham Cancer Center, Boston, MA, USA.
Harvard Medical School, Boston, MA, USA.

Sandra M Swain (SM)

Georgetown University, Washington, DC, USA.

Paula Pohlmann (P)

MedStar Georgetown University Hospital, Washington, DC, USA.

Heather A Parsons (HA)

Division of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Breast Oncology Program, Dana-Farber Brigham Cancer Center, Boston, MA, USA.
Harvard Medical School, Boston, MA, USA.

Claudine Isaacs (C)

Georgetown University, Washington, DC, USA.

Classifications MeSH