Durvalumab with olaparib and paclitaxel for high-risk HER2-negative stage II/III breast cancer: Results from the adaptively randomized I-SPY2 trial
Durvalumab with olaparib and paclitaxel for high-risk HER2-negative stage II/III breast cancer: Results from the adaptively randomized I-SPY2 trial
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DOI：
10.1016/j.ccell.2021.05.009
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发表时间：
2021-07-12
期刊：
影响因子：
50.3
通讯作者：
Esserman, Laura J.
中科院分区：
文献类型：
--
作者：
Pusztai, Lajos;Yau, Christina;Esserman, Laura J.
在Ⅱ/Ⅲ期HER2阴性乳腺癌的II-I-SPY2期试验中，在标准紫杉醇新辅助化疗(杜伐单抗/奥拉帕布/紫杉醇[DOP])的基础上，研究了PD-L1抑制剂duvalumab和PARP抑制剂olaparib的联合应用。73名参与者被随机分为DOP组和299名标准护理(紫杉醇)对照组。DOP增加了HER2阴性(20%-37%)、激素受体(HR)阳性/HER2阴性(14%-28%)和三阴性乳腺癌(TNBC)(27%-47%)的病理完全应答(PCR)率。在HR阳性/HER2阴性的癌症中，乳腺癌MammaPrint超高(MP2)病例选择性地受益于DOP(PCR%对22%)，而MP1癌则没有好处(pCR9%对10%)。总体而言，DOP组12.3%的患者经历了与免疫相关的3级不良事件，而对照组为1.3%。与免疫反应相关的基因表达特征与双臂的聚合酶链式反应呈正相关，而肥大细胞特征与非聚合酶链式反应相关。DOP在HER2阴性乳腺癌中的疗效优于标准新辅助化疗，特别是在高风险HR阳性/HER2阴性患者中。
The combination of PD-L1 inhibitor durvalumab and PARP inhibitor olaparib added to standard paclitaxel neoadjuvant chemotherapy (durvalumab/olaparib/paclitaxel [DOP]) was investigated in the phase II I-SPY2 trial of stage II/III HER2-negative breast cancer. Seventy-three participants were randomized to DOP and 299 to standard of care (paclitaxel) control. DOP increased pathologic complete response (pCR) rates in all HER2-negative (20%-37%), hormone receptor (HR)-positive/HER2-negative (14%-28%), and triple-negative breast cancer (TNBC) (27%-47%). In HR-positive/HER2-negative cancers, MammaPrint ultra-high (MP2) cases benefited selectively from DOP(pCR 64% versus 22%), no benefit was seen in MP1 cancers (pCR9% versus 10%). Overall, 12.3% of patients in the DOP arm experienced immune-related grade 3 adverse events versus 1.3% in control. Gene expression signatures associated with immune response were positively associated with pCR in both arms, while a mast cell signature was associated with non-pCR. DOP has superior efficacy over standard neoadjuvant chemotherapy in HER2-negative breast cancer, particularly in a highly sensitive subset of high-risk HR-positive/HER2-negative patients.