Pathologic and molecular responses to neoadjuvant trastuzumab and/or lapatinib from a phase II randomized trial in HER2-positive breast cancer (TRIO-US B07).
Pathologic and molecular responses to neoadjuvant trastuzumab and/or lapatinib from a phase II randomized trial in HER2-positive breast cancer (TRIO-US B07).
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DOI：
10.1038/s41467-020-19494-2
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发表时间：
2020-11-17
影响因子：
16.6
通讯作者：
Slamon DJ
中科院分区：
文献类型：
--
作者：
Hurvitz SA;Caswell-Jin JL;McNamara KL;Zoeller JJ;Bean GR;Dichmann R;Perez A;Patel R;Zehngebot L;Allen H;Bosserman L;DiCarlo B;Kennedy A;Giuliano A;Calfa C;Molthrop D;Mani A;Chen HW;Dering J;Adams B;Kotler E;Press MF;Brugge JS;Curtis C;Slamon DJ
在这项由赛诺菲和葛兰素史克（TRIO-US B07，临床试验NCT00769470）资助的多中心、开放标签、随机II期研究人员赞助的新辅助试验中，来自13个美国肿瘤转化研究网络的早期her2阳性乳腺癌患者（N = 128）被招募。参与者随机接受曲妥珠单抗（T; N = 34）、拉帕替尼（L; N = 36）或两者（TL; N = 58）作为her2靶向治疗，每个参与者单独接受一个周期的这种指定的抗her2治疗，然后接受六个周期的标准联合化疗与相同的抗her2治疗。主要目的是估计手术时三组患者的病理完全缓解率（pCR）。在意向治疗人群中，我们观察到T组（47%，95%置信区间[CI] 30-65%）和TL组（52%,95% CI 38-65%）的pCR率相似，L组的pCR率较低（25%,95% CI 13-43%）。在T组中，100%的参与者在手术前完成了所有协议规定的治疗，而L组为69%，TL组为74%。在治疗前（N = 110）、单独her2靶向治疗一个周期后（N = 89）和手术时（N = 59）尽可能收集肿瘤或肿瘤床组织。较高水平的HER2扩增和激素受体（HR）阴性状态与较高的pCR率相关。在一个周期的her2靶向治疗后，肿瘤、免疫和基质基因表达发生了巨大的变化。与pCR率相比，在这个时间点，含l的臂比T表现出更大的增殖减少。在一个周期的her2靶向治疗后，所有手臂的免疫表达特征增加，在手术时再次下降。我们的研究结果为早期评估抗her2治疗的敏感性提供了信息，并揭示了免疫微环境在对her2靶向药物的反应中的作用。HER2阳性乳腺癌患者通常会对曲妥珠单抗产生耐药性，因此需要探索潜在的联合治疗方法。在这里，作者报告了一项多中心随机II期临床试验的结果，该试验评估了曲妥珠单抗和/或拉帕替尼联合化疗对HER2+乳腺癌患者的病理和分子反应。
In this multicenter, open-label, randomized phase II investigator-sponsored neoadjuvant trial with funding provided by Sanofi and GlaxoSmithKline (TRIO-US B07, Clinical Trials NCT00769470), participants with early-stage HER2-positive breast cancer (N = 128) were recruited from 13 United States oncology centers throughout the Translational Research in Oncology network. Participants were randomized to receive trastuzumab (T; N = 34), lapatinib (L; N = 36), or both (TL; N = 58) as HER2-targeted therapy, with each participant given one cycle of this designated anti-HER2 therapy alone followed by six cycles of standard combination chemotherapy with the same anti-HER2 therapy. The primary objective was to estimate the rate of pathologic complete response (pCR) at the time of surgery in each of the three arms. In the intent-to-treat population, we observed similar pCR rates between T (47%, 95% confidence interval [CI] 30–65%) and TL (52%, 95% CI 38–65%), and a lower pCR rate with L (25%, 95% CI 13–43%). In the T arm, 100% of participants completed all protocol-specified treatment prior to surgery, as compared to 69% in the L arm and 74% in the TL arm. Tumor or tumor bed tissue was collected whenever possible pre-treatment (N = 110), after one cycle of HER2-targeted therapy alone (N = 89), and at time of surgery (N = 59). Higher-level amplification of HER2 and hormone receptor (HR)-negative status were associated with a higher pCR rate. Large shifts in the tumor, immune, and stromal gene expression occurred after one cycle of HER2-targeted therapy. In contrast to pCR rates, the L-containing arms exhibited greater proliferation reduction than T at this timepoint. Immune expression signatures increased in all arms after one cycle of HER2-targeted therapy, decreasing again by the time of surgery. Our results inform approaches to early assessment of sensitivity to anti-HER2 therapy and shed light on the role of the immune microenvironment in response to HER2-targeted agents. HER2+ breast cancer patients can often develop resistance to trastuzumab and therefore potential combination therapies need to be explored. Here, the authors report the results of a multi-center randomized phase II clinical trial evaluating the pathological and molecular responses associated with trastuzumab and/or lapatinib in combination with chemotherapy in HER2+ breast cancer patients.
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影响因子：
28.4
作者：
Fumagalli D;Venet D;Ignatiadis M;Azim HA Jr;Maetens M;Rothé F;Salgado R;Bradbury I;Pusztai L;Harbeck N;Gomez H;Chang TW;Coccia-Portugal MA;Di Cosimo S;de Azambuja E;de la Peña L;Nuciforo P;Brase JC;Huober J;Baselga J;Piccart M;Loi S;Sotiriou C
通讯作者：
Sotiriou C
影响因子：
168.9
作者：
Gianni, Luca;Eiermann, Wolfgang;Baselga, Jose
通讯作者：
Baselga, Jose
影响因子：
11.5
作者：
Bardia, Aditya;Baselga, Jose
通讯作者：
Baselga, Jose
影响因子：
64.8
作者：
Curtis, Christina;Shah, Sohrab P.;Chin, Suet-Feung;Turashvili, Gulisa;Rueda, Oscar M.;Dunning, Mark J.;Speed, Doug;Lynch, Andy G.;Samarajiwa, Shamith;Yuan, Yinyin;Graef, Stefan;Ha, Gavin;Haffari, Gholamreza;Bashashati, Ali;Russell, Roslin;McKinney, Steven;Langerod, Anita;Green, Andrew;Provenzano, Elena;Wishart, Gordon;Pinder, Sarah;Watson, Peter;Markowetz, Florian;Murphy, Leigh;Ellis, Ian;Purushotham, Arnie;Borresen-Dale, Anne-Lise;Brenton, James D.;Tavare, Simon;Caldas, Carlos;Aparicio, Samuel
通讯作者：
Aparicio, Samuel
影响因子：
50.5
作者：
Bonnefoi, H.;Jacot, W.;Cameron, D.
通讯作者：
Cameron, D.