Trastuzumab for early-stage, HER2-positive breast cancer: a meta-analysis of 13 864 women in seven randomised trials.
Trastuzumab for early-stage, HER2-positive breast cancer: a meta-analysis of 13 864 women in seven randomised trials.
复制标题
DOI：
10.1016/s1470-2045(21)00288-6
复制
发表时间：
2021-08
期刊：
影响因子：
--
通讯作者：
Early Breast Cancer Trialists’ Collaborative group (EBCTCG)
中科院分区：
文献类型：
--
作者：
Early Breast Cancer Trialists’ Collaborative group (EBCTCG)
曲妥珠单抗针对HER2蛋白的胞外区域。对于HER2阳性的早期乳腺癌患者，在化疗中加入曲妥珠单抗可以降低复发和死亡的风险，但与心脏毒性有关。我们调查了辅助剂曲妥珠单抗对乳腺癌复发和特定原因死亡率的长期益处和风险。我们对来自随机试验的个体患者数据进行了协作性荟萃分析，评估化疗加曲妥珠单抗与单独使用相同的化疗。纳入了招募患有结节阴性或结节阳性、可手术乳腺癌的妇女的随机试验。我们收集了个体患者水平的数据，包括基线特征、首次远处乳腺癌复发的日期和地点、以前的任何局部复发或第二次原发癌，以及死亡日期和潜在原因。主要结果是乳腺癌复发、乳腺癌死亡率、无复发死亡和全因死亡率。按年龄、结节状态、雌激素受体(ER)状态和试验分层的标准意向治疗对数等级分析得出首次事件比(RR)。7项随机试验符合纳入标准，包括在2000年2月至2005年12月期间登记的13名 864患者。平均疗程14.4个月，中位随访期10.7年(IQR9.5~11.9)。曲妥珠单抗联合化疗的乳腺癌复发风险(RR 0·66，95%CI 0·62~0·71；P<；0·0001)和乳腺癌死亡率(0·67，0·61~0·73；P<；0·0001)均低于单纯化疗。10年绝对复发风险降低9.0%(95%可信区间7·4~10.7；P<；0·0001)，10年乳腺癌死亡率降低6.4%(4·9~7·8；P<；0·0001)，全因死亡率降低6.5%(5·0~8·0；P<；0·0001)，无复发死亡率无增加(0·4%，-0·3~1·1；P=0·35)。随机化后0-1年复发率下降幅度最大(0.53，99%可信区间0.46-0.61)，疗效持续到2-4年(0.73，0.62-0.85)和5-9年(0.80，0·-1.01)，10年后几乎没有随访。复发率下降比例与记录中的患者和肿瘤特征，包括ER状态无关。肿瘤风险越高，5年复发率的绝对减少率越大(例如，N0、N1-3和N4+病的5·7%[95%CI 3·1~8·3]、6·8%[4·7~9·0]和10·7%[7·7~13·6])。在HER2阳性的早期乳腺癌的化疗中加入曲妥珠单抗，可以将乳腺癌的复发和死亡率降低三分之一，无论记录的患者和肿瘤特征如何，都有价值的比例降低。英国癌症研究中心，英国医学研究委员会。
Trastuzumab targets the extracellular domain of the HER2 protein. Adding trastuzumab to chemotherapy for patients with early-stage, HER2-positive breast cancer reduces the risk of recurrence and death, but is associated with cardiac toxicity. We investigated the long-term benefits and risks of adjuvant trastuzumab on breast cancer recurrence and cause-specific mortality. We did a collaborative meta-analysis of individual patient data from randomised trials assessing chemotherapy plus trastuzumab versus the same chemotherapy alone. Randomised trials that enrolled women with node-negative or node-positive, operable breast cancer were included. We collected individual patient-level data on baseline characteristics, dates and sites of first distant breast cancer recurrence and any previous local recurrence or second primary cancer, and the date and underlying cause of death. Primary outcomes were breast cancer recurrence, breast cancer mortality, death without recurrence, and all-cause mortality. Standard intention-to-treat log-rank analyses, stratified by age, nodal status, oestrogen receptor (ER) status, and trial yielded first-event rate ratios (RRs). Seven randomised trials met the inclusion criteria, and included 13 864 patients enrolled between February, 2000, and December, 2005. Mean scheduled treatment duration was 14·4 months and median follow-up was 10·7 years (IQR 9·5 to 11·9). The risks of breast cancer recurrence (RR 0·66, 95% CI 0·62 to 0·71; p<0·0001) and death from breast cancer (0·67, 0·61 to 0·73; p<0·0001) were lower with trastuzumab plus chemotherapy than with chemotherapy alone. Absolute 10-year recurrence risk was reduced by 9·0% (95% CI 7·4 to 10·7; p<0·0001) and 10-year breast cancer mortality was reduced by 6·4% (4·9 to 7·8; p<0·0001), with a 6·5% reduction (5·0 to 8·0; p<0·0001) in all-cause mortality, and no increase in death without recurrence (0·4%, –0·3 to 1·1; p=0·35). The proportional reduction in recurrence was largest in years 0–1 after randomisation (0·53, 99% CI 0·46 to 0·61), with benefits persisting through years 2–4 (0·73, 0·62 to 0·85) and 5–9 (0·80, 0·64 to 1·01), and little follow-up beyond year 10. Proportional recurrence reductions were similar irrespective of recorded patient and tumour characteristics, including ER status. The more high risk the tumour, the larger the absolute reductions in 5-year recurrence (eg, 5·7% [95% CI 3·1 to 8·3], 6·8% [4·7 to 9·0], and 10·7% [7·7 to 13·6] in N0, N1–3, and N4+ disease). Adding trastuzumab to chemotherapy for early-stage, HER2-positive breast cancer reduces recurrence of, and mortality from, breast cancer by a third, with worthwhile proportional reductions irrespective of recorded patient and tumour characteristics. Cancer Research UK, UK Medical Research Council.