TY - JOUR
T1 - Adjuvant nivolumab, capecitabine or the combination in patients with residual triple-negative breast cancer
T2 - the OXEL randomized phase II study
AU - Lynce, Filipa
AU - Mainor, Candace
AU - Donahue, Renee N.
AU - Geng, Xue
AU - Jones, Greg
AU - Schlam, Ilana
AU - Wang, Hongkun
AU - Toney, Nicole J.
AU - Jochems, Caroline
AU - Schlom, Jeffrey
AU - Zeck, Jay
AU - Gallagher, Christopher
AU - Nanda, Rita
AU - Graham, Deena
AU - Stringer-Reasor, Erica M.
AU - Denduluri, Neelima
AU - Collins, Julie
AU - Chitalia, Ami
AU - Tiwari, Shruti
AU - Nunes, Raquel
AU - Kaltman, Rebecca
AU - Khoury, Katia
AU - Gatti-Mays, Margaret
AU - Tarantino, Paolo
AU - Tolaney, Sara M.
AU - Swain, Sandra M.
AU - Pohlmann, Paula
AU - Parsons, Heather A.
AU - Isaacs, Claudine
N1 - Publisher Copyright:
© The Author(s) 2024.
PY - 2024/12
Y1 - 2024/12
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85188950021&partnerID=8YFLogxK
U2 - 10.1038/s41467-024-46961-x
DO - 10.1038/s41467-024-46961-x
M3 - Article
C2 - 38538574
AN - SCOPUS:85188950021
SN - 2041-1723
VL - 15
JO - Nature Communications
JF - Nature Communications
IS - 1
M1 - 2691
ER -