Breast Medical Oncology, Yale Cancer Center, Yale School of Medicine, 333 Cedar Steet, PO Box 208032, New Haven, CT 06510, USA.
Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, CA 94143, USA.
Cancer Cell. 2021 Jul 12;39(7):989-998.e5. doi: 10.1016/j.ccell.2021.05.009. Epub 2021 Jun 17.
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 (pCR 9% 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.
在 II 期 I-SPY2 试验中，研究了 PD-L1 抑制剂度伐利尤单抗和 PARP 抑制剂奥拉帕利联合标准紫杉醇新辅助化疗（度伐利尤单抗/奥拉帕利/紫杉醇[DOP]）在 II/III 期 HER2 阴性乳腺癌中的应用。73 名参与者被随机分配到 DOP 组，299 名参与者被分配到标准护理（紫杉醇）对照组。DOP 增加了所有 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%）患者的病理完全缓解（pCR）率。在 HR 阳性/HER2 阴性癌症中，MammaPrint 超高（MP2）病例选择性地从 DOP 中受益（pCR 为 64%对 22%），MP1 病例则未受益（pCR 为 9%对 10%）。总体而言，DOP 组有 12.3%的患者发生免疫相关 3 级不良事件，而对照组为 1.3%。与对照组相比，DOP 组和对照组中与免疫反应相关的基因表达特征均与 pCR 呈正相关，而肥大细胞特征与非 pCR 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 HR 阳性/HER2 阴性高风险的高度敏感亚组患者中。
