小柯机器人

美国耶鲁医学院Lajos Pusztai等研究人员完成durvalumab联合奥拉帕尼和紫杉醇治疗高危HER2阴性II/III期乳腺癌的临床试验。2021年6月17日，《癌细胞》杂志在线发表了这项成果。

在II/III期HER2 阴性乳腺癌的II期I-SPY2试验中，研究人员测试了在标准紫杉醇新辅助化疗中加入PD-L1抑制剂durvalumab和PARP抑制剂奥拉帕尼的组合（durvalumab/奥拉帕尼/紫杉醇 [DOP]）。73名参与者被随机分配到DOP，299名参与者被随机分配到标准护理（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）的病理完全缓解（pCR）率（27%–47%）。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 64%对22%），在MP1癌症中没有看到任何益处（pCR 9%对10%）。

总体而言，DOP组中有12.3%的患者经历了免疫相关的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，尤其是在高危HR阳性/HER2阴性患者的高度敏感亚组中。

附：英文原文

Title: Durvalumab with olaparib and paclitaxel for high-risk HER2-negative stage II/III breast cancer: Results from the adaptively randomized I-SPY2 trial

Author: Lajos Pusztai, Christina Yau, Denise M. Wolf, Hyo S. Han, Lili Du, Anne M. Wallace, Erica String-Reasor, Judy C. Boughey, A. Jo Chien, Anthony D. Elias, Heather Beckwith, Rita Nanda, Kathy S. Albain, Amy S. Clark, Kathleen Kemmer, Kevin Kalinsky, Claudine Isaacs, Alexandra Thomas, Rebecca Shatsky, Theresa L. Helsten, Andres Forero-Torres, Minetta C. Liu, Lamorna Brown-Swigart, Emmanuel F. Petricoin, Julia D. Wulfkuhle, Smita M. Asare, Amy Wilson, Ruby Singhrao, Laura Sit, Gillian L. Hirst, Scott Berry, Ashish Sanil, Adam L. Asare, Jeffrey B. Matthews, Jane Perlmutter, Michelle Melisko, Hope S. Rugo, Richard B. Schwab, W. Fraser Symmans, Doug Yee, Laura J. van’t Veer, Nola M. Hylton, Angela M. DeMichele, Donald A. Berry, Laura J. Esserman

Issue&Volume: 2021-06-17

Abstract: The combination of PD-L1 inhibitor durvalumab and PARP inhibitor olaparib added tostandard paclitaxel neoadjuvant chemotherapy (durvalumab/olaparib/paclitaxel [DOP])was investigated in the phase II I-SPY2 trial of stage II/III HER2-negative breastcancer. Seventy-three participants were randomized to DOP and 299 to standard of care(paclitaxel) control. DOP increased pathologic complete response (pCR) rates in allHER2-negative (20%–37%), hormone receptor (HR)-positive/HER2-negative (14%–28%), andtriple-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 patientsin the DOP arm experienced immune-related grade 3 adverse events versus 1.3% in control.Gene expression signatures associated with immune response were positively associatedwith pCR in both arms, while a mast cell signature was associated with non-pCR. DOPhas superior efficacy over standard neoadjuvant chemotherapy in HER2-negative breastcancer, particularly in a highly sensitive subset of high-risk HR-positive/HER2-negativepatients.

DOI: 10.1016/j.ccell.2021.05.009

Source: https://www.cell.com/cancer-cell/fulltext/S1535-6108(21)00275-0

Cancer Cell：《癌细胞》，创刊于2002年。隶属于细胞出版社，最新IF：38.585
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