基于临床前数据，综合周期性死亡蛋白1 （PD-1）和环依赖性激酶4/6（CDK4/6）阻断在雌激素受体阳性/人表皮生长因子受体2阴性（ER+/HER2-）乳腺癌中表现出协同作用。非比较性1b/2 CheckMate 7A8研究（NCT04075604）评估了尼伐替尤单抗（nivolumab）、帕博西尼（palbociclib）和阿那曲唑（anastrozole）在ER+/HER2-乳腺癌患者中的新辅助治疗效果。本文报告了安全性试行阶段的结果。符合组织学诊断为未治疗的ER+/HER2-乳腺癌、原发肿瘤≥2厘米、ECOG疗效评分≤1且符合术后治疗条件的患者接受尼伐替尤单抗480毫克静脉注射，帕博西尼每天口服125毫克或100毫克，每个周期3周，阿那曲唑每天口服1毫克，连续五个4周周期，或直到疾病进展。主要终点为4周内出现剂量限制性毒性（DLT）的患者比例。在安全性数据审核时，共治疗了21例患者（帕博西尼125毫克组：n=9；帕博西尼100毫克组：n=12）。帕博西尼125毫克组有2例（22.2%）患者报道了DLTs，帕博西尼100毫克组无患者报道DLTs。两组中共有9例患者因毒性副作用中断治疗（级别3/4的肝毒性不良事件[n=6]，级别3的退热性粒细胞减少症[n=1]，级别1的肺炎[n=1]，级别3的皮疹和级别2的免疫介导性肺炎[n=1]）。因此，该研究被提前终止。尼伐替尤单抗、帕博西尼和阿那曲唑的新辅助治疗显示出高发生率的级别3/4肝毒性并出现治疗中断，表明该联合应不再进一步用于治疗原发ER+/HER2-乳腺癌。©2023作者。版权归科学出版社所有。保留所有权利。

Preclinical data suggest synergistic activity with the combination of programmed death-1 and cyclin-dependent kinase 4/6 blockade in oestrogen receptor-positive/human epidermal growth factor 2-negative (ER+/HER2-) breast cancer. The noncomparative phase 1b/2 CheckMate 7A8 study (NCT04075604) evaluated neoadjuvant treatment with nivolumab, palbociclib, and anastrozole in patients with ER+/HER2- breast cancer. Here, we report outcomes from the safety run-in phase.Patients with histologically confirmed, untreated ER+/HER2- breast cancer, primary tumour ≥2 cm, ECOG performance status ≤1, and eligible for post-treatment surgery received nivolumab 480 mg intravenously every 4 weeks, palbociclib 125 mg or 100 mg orally once daily for 3 weeks per cycle, and anastrozole 1 mg orally once daily for five 4-week cycles, or until disease progression. The primary endpoint was the proportion of patients with dose-limiting toxicities (DLTs) within 4 weeks of treatment initiation.At safety data review, 21 patients were treated (palbociclib 125-mg group: n = 9; palbociclib 100-mg group: n = 12). DLTs were reported in 2 (22.2%) and 0 patients in the palbociclib 125-mg and 100-mg groups, respectively. Across both groups, 9 patients discontinued treatment due to toxicity (grade 3/4 hepatic adverse events [n = 6], grade 3 febrile neutropaenia [n = 1], grade 1 pneumonitis [n = 1], and grade 3 rash and grade 2 immune-mediated pneumonitis [n = 1]). Consequently, the study was closed early.Neoadjuvant treatment with nivolumab, palbociclib, and anastrozole showed a high incidence of grade 3/4 hepatotoxicity and treatment discontinuation, indicating that this combination should not be further pursued for treatment of primary ER+/HER2- breast cancer.Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.