Neoadjuvant nivolumab and chemotherapy in early estrogen receptor-positive breast cancer: a randomized phase 3 trial
- Author(s)
- Loi, S; Salgado, R; Curigliano, G; Romero Díaz, RI; Delaloge, S; Rojas García, CI; Kok, M; Saura, C; Harbeck, N; Mittendorf, EA; Yardley, DA; Suárez Zaizar, A; Caminos, FR; Ungureanu, A; Reinoso-Toledo, JG; Guarneri, V; Egle, D; Ades, F; Pacius, M; Chhibber, A; Chandra, R; Nathani, R; Spires, T; Wu, JQ; Pusztai, L; McArthur, H;
- Journal Title
- Nature Medicine
- Publication Type
- Online publication before print
- Abstract
- Patients with estrogen receptor-positive (ER+), human epidermal growth factor receptor 2-negative (HER2-) primary breast cancer (BC) have low pathological complete response (pCR) rates with neoadjuvant chemotherapy. A subset of ER+/HER2- BC contains dense lymphocytic infiltration. We hypothesized that addition of an anti-programmed death 1 agent may increase pCR rates in this BC subtype. We conducted a randomized, multicenter, double-blind phase 3 trial to investigate the benefit of adding nivolumab to neoadjuvant chemotherapy in patients with newly diagnosed, high-risk, grade 3 or 2 (ER 1 to ≤10%) ER+/HER2- primary BC. In total, 510 patients were randomized to receive anthracycline and taxane-based chemotherapy with either intravenous nivolumab or placebo. The primary endpoint of pCR was significantly higher in the nivolumab arm compared with placebo (24.5% versus 13.8%; P = 0.0021), with greater benefit observed in patients with programmed death ligand 1-positive tumors (VENTANA SP142 ≥1%: 44.3% versus 20.2% respectively). There were no new safety signals identified. Of the five deaths that occurred in the nivolumab arm, two were related to study drug toxicity; no deaths occurred in the placebo arm. Adding nivolumab to neoadjuvant chemotherapy significantly increased pCR rates in high-risk, early-stage ER+/HER2- BC, particularly among patients with higher stromal tumor-infiltrating lymphocyte levels or programmed death ligand 1 expression, suggesting a new treatment paradigm that emphasizes the role of immunotherapy and T cell immunosurveillance in luminal disease. Clinical trials.gov identifier: NCT04109066.
- Department(s)
- Medical Oncology
- Publisher's Version
- https://doi.org/10.1038/s41591-024-03414-8
- Open Access at Publisher's Site
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Creation Date: 2025-01-28 02:47:09
Last Modified: 2025-01-28 02:54:38