Neoadjuvant nivolumab and chemotherapy in early estrogen receptor-positive breast cancer: a randomized phase 3 trial

Loi, S; Salgado, R; Curigliano, G; Romero D&#237;az, RI; Delaloge, S; Rojas Garc&#237;a, CI; Kok, M; Saura, C; Harbeck, N; Mittendorf, EA; Yardley, DA; Su&#225;rez 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

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;
Details: Publication Year 2025-02,Volume 31,Issue #2,Page 433-441
Journal Title: Nature Medicine
Publication Type: Research article
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.
Keywords: Humans; Female; *Breast Neoplasms/drug therapy/pathology/genetics; *Nivolumab/administration & dosage/therapeutic use/adverse effects; *Neoadjuvant Therapy; *Receptors, Estrogen/metabolism; Middle Aged; *Antineoplastic Combined Chemotherapy Protocols/therapeutic use/adverse effects; Aged; Adult; Receptor, ErbB-2/metabolism/genetics; Double-Blind Method; Anthracyclines/therapeutic use/administration & dosage; B7-H1 Antigen/antagonists & inhibitors/metabolism
Department(s): Medical Oncology; Laboratory Research
Publisher's Version: https://doi.org/10.1038/s41591-024-03414-8
Open Access at Publisher's Site: https://doi.org/10.1038/s41591-024-03414-8
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2025-01-28 02:47:09

Last Modified: 2025-03-21 02:55:13