Neoadjuvant Pertuzumab-containing Regimens Improve Pathologic Complete Response Rates in Stage II to III HER-2/neu-positive Breast Cancer: A Retrospective,Single Institution Experience

Introduction

Several human epidermal growth factor 2 (HER2)-targeted regimens are used to treat HER2-positive (HER2⁺) breast cancer (BC). The goal of this study was to retrospectively determine the pathologic complete response (pCR) rate for trastuzumab and pertuzumab (HP)-containing regimens compared with trastuzumab (H)-containing regimens for stage II to III HER2⁺ BC.

拉帕替尼联合曲妥珠单抗治疗HER2阳性乳腺癌的疗效观察

目的探讨拉帕替尼联合曲妥珠单抗治疗HER2阳性乳腺癌患者的临床效果。方法选取2011年1月—2014年3月在宝鸡市妇幼保健院接受治疗的261例乳腺癌患者,随机分为拉帕替尼组(82例)、曲妥珠单抗组(84例)和联合组(95例),3组患者中途各有3、2和1例停止治疗。拉帕替尼组口服拉帕替尼片,6片/次,1次/d;曲妥珠单抗组静脉注射注射用曲妥珠单抗,1次/周,前9周4 mg/kg,后9周2 mg/kg维持;联合组治疗方法是上述两组治疗方法的联用,3组均连续治疗18周。治疗后,观察3组患者临床疗效,同时比较3组治疗前后无进展生存率(PFS)、总生存期(OS)、中枢神经系统(CNS)转移情况、总反应率(ORR)、临床受益反应(CBR)以及不良反应变化情况。结果治疗后,拉帕替尼组治愈率为21.52%,控制率为51.90%;曲妥珠单抗组治愈率为24.39%,控制率为57.32%;联合组治愈率为45.74%,控制率为76.60%,3组治愈率比较差异具有统计学意义(P0.05),控制率比较差异具有统计学意义(P0.01)。治疗后,拉帕替尼组、曲妥珠单抗组和联合组的PFS分别为41、43、55个月,联合组PFS比拉帕替尼组和曲妥珠单抗组均显著延长,差异具有统计学意义(P0.05)。治疗后随访期间拉帕替尼组(72例)、曲妥珠单抗组(76例)和联合组(83例)的PFS分别为24、26、36个月,联合组的PFS比拉帕替尼组、曲妥珠单抗组的均显著延长,差异具有统计学意义(P0.05)。治疗后,拉帕替尼组、曲妥珠单抗组和联合组的CNS转移率分别为32.91%、29.27%、19.15%,联合组的CNS转移率明显低于拉帕替尼组和曲妥珠单抗组,差异具有统计学意义(P0.05)。拉帕替尼组、曲妥珠单抗组和联合组的ORR分别为56.96%、59.76%、76.60%,联合组ORR均高于拉帕替尼组、曲妥珠单抗组,差异具有统计学意义(P0.05)。拉帕替尼组、曲妥珠单抗组和联合组的CBR分别为43.04%、47.56%、69.15%,联合组的均高于拉帕替尼组、曲妥珠单抗组,差异具有统计学意义(P0.05)。联合组的不良反应发生率显著低于拉帕替尼组和曲妥珠单抗组,差异比较具有统计学意义(P0.05)。结论拉帕替尼联合曲妥珠单抗对HER2阳性乳腺癌患者具有较好的临床治疗效果,具有一定的临床推广应用价值。     

Trastuzumab therapy in Australia: Which patients with HER2+ metastatic breast cancer are assessed for cardiac function?

PurposeTo manage the potential trastuzumab mediated cardiotoxicity, clinical guidelines recommend pre-treatment cardiac function assessment and 3-monthly reassessment during therapy. This study examined rates of cardiac function assessment and predictors of assessment among patients receiving trastuzumab for HER2+ metastatic breast cancer treatment in routine clinical care.MethodsOur cohort comprised 3418 women receiving trastuzumab for HER2+ metastatic breast cancer under Australia's nationally funded Herceptin Program (2001–2010). We examined rates of pre-treatment and during-treatment assessment. We used logistic regression and zero-inflated Poisson regression to examine predictors of pre-treatment and during-treatment assessment respectively.Results37.7% of patients were assessed pre-treatment, 50.4% during therapy, and 26.4% both before and during therapy. Among patients assessed for cardiac function, reassessment occurred regularly (median of 3.9 months). History of cardiovascular conditions and prior anthracycline use predicted pre-treatment assessment (OR = 1.32, 95% CI: 1.08–1.61; OR = 1.23, 95% CI: 1.05–1.44 respectively). Concurrent trastuzumab and taxane use, exposure to anthracyclines, and older age predicted during-treatment assessment (IRR = 1.17, 95% CI: 1.06–1.29; IRR = 1.12, 95% CI: 1.02–1.23; and IRR = 1.05, 95% CI: 1.01–1.09 respectively). Patients with multi-morbidities were less likely to receive during-treatment assessment.ConclusionOver the last decade, cardiac function assessment in a large cohort of patients receiving trastuzumab was not consistent with guideline recommendations. The association between cardiac monitoring and risk factors for cardiac dysfunction suggest clinicians are triaging patients prior to implementing cardiac assessment. Efforts are needed to identify barriers to implementing current guidelines for cardiac monitoring in metastatic breast cancer patients undergoing trastuzumab treatment, particularly those with multi-morbidities.     

HER2 Assessment in Upper Gastrointestinal Tract Adenocarcinoma: A Practical,Algorithmic Approach

Gastric and gastroesophageal junction adenocarcinomas constitute a major health problem. For localized disease, adjuvant treatment is multidisciplinary and usually includes a combination of surgery, radiation and chemotherapy. Recently, trastuzumab (Herceptin) has been approved for the treatment of metastatic upper gastrointestinal (GI) tract (gastric, esophageal, and gastroesophageal) adenocarcinomas. The purpose of this review is to provide pathologists with practical guidance in HER2 assessment of upper GI tract adenocarcinomas in order to accurately identify patients eligible for trastuzumab therapy.     

曲妥珠单抗和帕妥珠单抗联合化疗对HER2阳性乳腺癌新辅助治疗的真实世界研究

目的 分析曲妥珠单抗(H)和帕妥珠单抗(P)联合化疗对HER2阳性乳腺癌新辅助治疗的疗效和安全性.方法 回顾性分析行HP联合化疗新辅助治疗并完成手术的HER2阳性乳腺癌患者的临床资料,主要研究终点为总体病理完全缓解(tpCR)(ypT0/isypN0),次要研究终点为乳腺病理完全缓解(bpCR)(ypT0/is)和腋窝...     

The bioanalysis of the monoclonal antibody trastuzumab by high-performance liquid chromatography with fluorescence detection after immuno-affinity purification from human serum

For the quantification of therapeutic monoclonal antibodies in biological specimens, enzyme-linked immunosorbent assay (ELISA) is the most widely used technique. ELISA's have some limitations and therefore alternative analytical techniques are being explored. In this study we describe the development of a bioanalytical assay using high-performance liquid chromatography (HPLC) coupled with fluorescence detection for the bioanalysis of the monoclonal antibody trastuzumab. Different extraction procedures were explored, like isolation using protein A and protein G. Finally a method using immuno-affinity purification has been developed. Trastuzumab is isolated from human serum using sepharose coupled with anti-trastuzumab idiotype antibodies. After extraction samples are injected onto a Zorbax 300SB C₈ column at 75 °C using the organic solvents isopropanol and acetonitrile with high eluotropic strengths. The assay quantifies trastuzumab from 5 to 40 μg/mL in human serum with accuracies <20%. Samples with concentrations above the upper limit of quantification (>ULOQ; >40 μg/mL) can be diluted 5 times with control human serum prior to sample pre-treatment. The assay can now be used to analyse serum samples of patients treated with trastuzumab. The obtained results are comparable to those obtained using ELISA. This is the first report describing a bioanalytical assay using HPLC and fluorescence detection for the quantification of a monoclonal antibody at the intact protein level in human serum. This unique approach has the advantage compared to ELISA that a HPLC separation step is introduced to improve the selectivity. This method is a potential alternative to ELISA to support pharmacokinetic evaluations. However, for purification of trastuzumab from serum anti-idiotype antibodies are necessary. These anti-idiotype antibodies are also used in ELISA and as ELISA is more sensitive and less labor-intensive, ELISA probably remains the analytical technique of first choise.     

抗Trastuzumab单克隆抗体制备及其双抗体夹心ELISA检测方法的建立

本研究利用曲妥珠单抗(Trastuzumab)4次腹腔免疫 6-8 周龄BALB/c 雌性小鼠.通过淋巴细胞杂交瘤技术、间接ELISA 筛选技术及腹水制备等技术制备并获得抗Trastuzumab单克隆抗体.试验结果表明,通过细胞融合获得了一株能稳定分泌抗Trastuzumab的杂交瘤细胞株A6E8,其制备的腹水单克隆抗体纯化后效价为256000,该抗体属于IgG1亚类,链的类型为k链.利用制备的单克隆抗体(McAb)建立Trastuzumab双抗体夹心ELISA检测方法,试验结果显示,该检测方法特异性良好,不与其他抗体及蛋白发生交叉反应,所建立的Trastuzumab双抗体夹心ELISA 方法最低检测限为1ng/mL.