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| Ref Type | Journal Article | ||||||||||||
| PMID | (39838118) | ||||||||||||
| Authors | 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 | ||||||||||||
| Title | Neoadjuvant nivolumab and chemotherapy in early estrogen receptor-positive breast cancer: a randomized phase 3 trial. | ||||||||||||
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| Abstract Text | 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. | ||||||||||||
| Molecular Profile | Treatment Approach |
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| Gene Name | Source | Synonyms | Protein Domains | Gene Description | Gene Role |
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| Therapy Name | Drugs | Efficacy Evidence | Clinical Trials |
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| Drug Name | Trade Name | Synonyms | Drug Classes | Drug Description |
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| Gene | Variant | Impact | Protein Effect | Variant Description | Associated with drug Resistance |
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| Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
|---|---|---|---|---|---|---|---|
| CD274 positive | estrogen-receptor positive breast cancer | predicted - sensitive | Anthracycline + Cyclophosphamide + Nivolumab + Paclitaxel | Phase III | Actionable | In a Phase III trial (CheckMate 7FL), the addition of Opdivo (nivolumab) to neoadjuvant chemotherapy with Taxol (paclitaxel) for 12 weeks followed by Opdivo (nivolumab) plus Cytoxan (cyclophosphamide) and Anthracycline resulted in improved pathologic complete response rate (44.3% vs 20.2%) compared to placebo plus neoadjuvant chemotherapy in patients with high-risk, early stage, ER (ESR1)-positive, CD274 (PD-L1)-positive (CPS>=1%), ERBB2 (HER2)-negative breast cancer (PMID: 39838118; NCT04109066). | 39838118 |