Dall Peter, Koch Thorsten, Göhler Thomas, Selbach Johannes, Ammon Andreas, Eggert Jochen, Gazawi Nidal, Rezek Daniela, Wischnik Arthur, Hielscher Carsten, Keitel Stella, Cirrincione Ursula, Hinke Axel, Feisel-Schwickardi Gabriele
Department of Obstetrics and Gynaecology and Breast Cancer Center, Klinikum Lüneburg, Lüneburg, Germany
Breast Center, Klinikum Nürnberg, Nürnberg, Germany.
Oncologist. 2017 Feb;22(2):131-138. doi: 10.1634/theoncologist.2016-0193. Epub 2017 Feb 7.
Trastuzumab is part of the standard treatment in patients with human epidermal growth factor receptor 2-positive early breast cancer in addition to (neo)adjuvant chemotherapy. This German prospective noninterventional study, which included major patient cohorts underrepresented in the pivotal randomized studies, examined the generalizability of the results of those studies.
Between 2006 and 2012, 4,027 patients were enrolled and treated with trastuzumab; they were unselected regarding age or concomitant/sequential adjuvant chemotherapy. Long-term outcome data were obtained in yearly intervals. All analyses were descriptive in nature.
Among 3,940 evaluable patients, 26% were elderly (older than 65 years of age). More than half of the population had pN0 tumor stage. Ninety-four percent received chemotherapy: 78% as adjuvant treatment and 14% as neoadjuvant treatment, 2% both. Anthracyclines were administered in 87% and taxanes in 66%. Trastuzumab was stopped prematurely in 9% (because of cardiotoxicity in 3.5%). Recurrence-free survival was 90.0% (95% confidence interval [CI], 88.9%-91.1%) and 82.8% (95% CI, 81.2%-84.4%) after 3 and 5 years, respectively. The corresponding figures for overall survival were 96.8% (95% CI, 96.1%-97.6%) and 90.0% (95% CI, 88.6%-91.4%). Pathological primary tumor size, lymph node involvement, and hormone receptor status had the greatest independent effect on recurrence risk. Cardiac function toxicity of National Cancer Institute common toxicity criteria grade ≥2 and ≥3 was observed in 2.5% and less than 1% of patients, respectively.
The maturing follow-up data seem to confirm the beneficial results of trastuzumab treatment for early breast cancer from the randomized studies. Moreover, these findings support use of trastuzumab-based therapy in patients groups less commonly included in the phase III trials (e.g., elderly patients and those with stage I disease). 2017;22:131-138 On the basis of the results of large pivotal phase III studies, the inclusion of trastuzumab in adjuvant treatment regimens for human epidermal growth factor receptor 2-positive breast cancer is standard of care. However, in these trials, elderly patients, those with comorbidities, and/or those with contraindications or refusal of cytotoxic chemotherapy are typically underrepresented. This study provides data on observed treatment options, outcomes, and risks in a wider, unselected patient population (including more than 1,000 patients with stage I disease), treated routinely in several institutions of varying size and location across Germany.
除（新）辅助化疗外，曲妥珠单抗是人类表皮生长因子受体2阳性早期乳腺癌患者标准治疗的一部分。这项德国前瞻性非干预性研究纳入了关键随机研究中代表性不足的主要患者队列，检验了这些研究结果的可推广性。
2006年至2012年期间，4027例患者入组并接受曲妥珠单抗治疗；他们在年龄或伴随/序贯辅助化疗方面未作选择。每年获取长期结局数据。所有分析本质上都是描述性的。
在3940例可评估患者中，26%为老年患者（年龄大于65岁）。超过一半的患者肿瘤分期为pN0。94%的患者接受了化疗：78%作为辅助治疗，14%作为新辅助治疗，2%两者皆有。87%的患者使用了蒽环类药物，66%使用了紫杉烷类药物。9%的患者曲妥珠单抗提前停药（3.5%是因为心脏毒性）。3年和5年后的无复发生存率分别为90.0%（95%置信区间[CI]，88.9%-91.1%）和82.8%（95%CI，81.2%-84.4%）。总生存率的相应数字分别为96.8%（95%CI，96.1%-97.6%）和90.0%（95%CI，88.6%-91.4%）。病理原发肿瘤大小、淋巴结受累情况和激素受体状态对复发风险的独立影响最大。分别有2.5%和不到1%的患者观察到美国国立癌症研究所常见毒性标准≥2级和≥3级的心脏功能毒性。
不断成熟的随访数据似乎证实了随机研究中曲妥珠单抗治疗早期乳腺癌的有益结果。此外，这些发现支持在III期试验中较少纳入的患者群体（如老年患者和I期疾病患者）中使用基于曲妥珠单抗的治疗。2017年；22:131 - 138基于大型关键III期研究的结果，将曲妥珠单抗纳入人类表皮生长因子受体2阳性乳腺癌的辅助治疗方案是标准治疗。然而，在这些试验中，老年患者、合并症患者和/或有细胞毒性化疗禁忌证或拒绝接受细胞毒性化疗的患者通常代表性不足。本研究提供了在德国不同规模和地点的多个机构常规治疗的更广泛、未作选择的患者群体（包括1000多名I期疾病患者）中观察到的治疗选择、结局和风险的数据。
