Bartlett John M S, Ahmed Ikhlaaq, Regan Meredith M, Sestak Ivana, Mallon Elizabeth A, Dell'Orto Patrizia, Thürlimann Beat, Seynaeve Caroline, Putter Hein, Van de Velde Cornelis J H, Brookes Cassandra L, Forbes John F, Viale Giuseppe, Cuzick Jack, Dowsett Mitchell, Rea Daniel W
Transformative Pathology, Ontario Institute for Cancer Research (OICR), MaRS Centre, 661 University Avenue, Suite 510, Toronto, ON M5G 0A3, Canada; University of Edinburgh Cancer Research Centre, Institute of Genetics and Molecular Medicine, The University of Edinburgh, Western General Hospital, Crewe Road South, Edinburgh EH4 2XR, UK.
Cancer Research UK Clinical Trials Unit, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK.
Eur J Cancer. 2017 Jul;79:129-138. doi: 10.1016/j.ejca.2017.03.033. Epub 2017 May 8.
A meta-analysis of the effects of HER2 status, specifically within the first 2-3 years of adjuvant endocrine therapy, has the potential to inform patient selection for upfront aromatase inhibitor (AI) therapy or switching strategy tamoxifen followed by AI. The pre-existing standardisation of methodology for HER2 (immunohistochemistry/fluorescence in situ hybridization) facilitates analysis of existing data for this key marker.
Following a prospectively designed statistical analysis plan, patient data from 3 phase III trials Arimidex, Tamoxifen, Alone or in Combination Trial (ATAC), Breast International Group (BIG) 1-98 and Tamoxifen Exemestane Adjuvant Multicentre Trial (TEAM)] comparing an AI to tamoxifen during the first 2-3 years of adjuvant endocrine treatment were collected and a treatment-by-marker analysis of distant recurrence-free interval-censored at 2-3 years treatment - for HER2 status × AI versus tamoxifen treatment was performed to address the clinical question relating to efficacy of 'upfront' versus 'switch' strategies for AIs.
A prospectively planned, patient-level data meta-analysis across 3 trials demonstrated a significant treatment (AI versus tamoxifen) by marker (HER2) interaction in a multivariate analysis; (interaction hazard ratio [HR] = 1.61, 95% CI 1.01-2.57; p < 0.05). Heterogeneity between trials did not reach statistical significance. The HER2 negative (HER2-ve) group gained greater benefit from AI versus tamoxifen (HR = 0.70, 95% CI 0.56-0.87) than the HER2-positive (HER2+ve) group (HR = 1.13, 95% CI 0.75-1.71). However, the small number of HER2+ve cases (n = 1092 across the 3 trials) and distant recurrences (n = 111) may explain heterogeneity between trials.
A patient-level data meta-analysis demonstrated a significant interaction between HER2 status and treatment with AI versus tamoxifen in the first 2-3 years of adjuvant endocrine therapy. Patients with HER2-ve cancers experienced improved outcomes (distant relapse) when treated with upfront AI rather than tamoxifen, whilst patients with HER2+ve cancers fared no better or slightly worse in the first 2-3 years. However, the small number of HER2+ve cancers/events may explain a large degree of heterogeneity in the HER2+ve groups across all 3 trials. Other causes, perhaps related to subtle differences between AIs, cannot be excluded and warrant further exploration.
对HER2状态的影响进行荟萃分析，特别是在辅助内分泌治疗的前2至3年内，有可能为患者选择 upfront 芳香化酶抑制剂（AI）治疗或他莫昔芬序贯AI的转换策略提供依据。HER2（免疫组织化学/荧光原位杂交）方法的预先标准化有助于分析该关键标志物的现有数据。
根据前瞻性设计的统计分析计划，收集了三项III期试验（阿那曲唑、他莫昔芬单药或联合试验[ATAC]、国际乳腺癌研究组[BIG]1-98以及他莫昔芬依西美坦辅助多中心试验[TEAM]）中在辅助内分泌治疗的前2至3年中将AI与他莫昔芬进行比较的患者数据，并对HER2状态×AI与他莫昔芬治疗的2至3年治疗期远处无复发生存期进行治疗-标志物分析，以解决与AI的“upfront”与“转换”策略疗效相关的临床问题。
一项对三项试验进行的前瞻性计划的患者水平数据荟萃分析表明，在多变量分析中存在显著的治疗（AI与他莫昔芬）×标志物（HER2）相互作用；（相互作用风险比[HR]=1.61，95%CI 1.01-2.57；p<0.05）。试验间的异质性未达到统计学显著性。HER2阴性（HER2-ve）组与他莫昔芬相比，从AI中获益更大（HR=0.70，95%CI 0.56-0.87），而HER2阳性（HER2+ve）组（HR=1.13，95%CI 0.75-1.71）。然而，HER2+ve病例数量较少（三项试验中共1092例）以及远处复发病例较少（111例）可能解释了试验间的异质性。
一项患者水平数据荟萃分析表明，在辅助内分泌治疗的前2至3年中，HER2状态与AI和他莫昔芬治疗之间存在显著相互作用。HER2-ve癌症患者接受 upfront AI治疗而非他莫昔芬时，结局（远处复发）得到改善，而HER2+ve癌症患者在最初2至3年中情况没有更好或略差。然而，HER2+ve癌症/事件数量较少可能解释了所有三项试验中HER2+ve组的很大程度的异质性。其他原因，可能与AI之间的细微差异有关，不能排除，值得进一步探索。
Zotero 插件