University Hospital Charité, Dept. Hematology, Oncology, Tumor Immunology, Augustenburger Platz 1, Berlin, 13353, Germany.
Center for Hematology and Oncology Bethanien, Im Prüfling 17-19, Frankfurt/Main, 60389, Germany.
Eur J Cancer. 2021 Jun;150:268-277. doi: 10.1016/j.ejca.2021.03.045. Epub 2021 May 7.
Neratinib is approved in the European Union for extended adjuvant treatment of human epidermal growth factor receptor 2-positive/hormone receptor-positive (copositive) early breast cancer ≤1 year of completion of prior trastuzumab-based therapy. Here, we report analyses of the hormone receptor-positive subgroup (N = 1631) from the ExteNET trial performed for the German health technology assessment (HTA).
With 2 years of median follow-up, HTA analyses revealed a significant advantage in disease-free survival (DFS) for neratinib vs. placebo (absolute/relative risk reduction: 4.1/48.2%; hazard ratio [HR] [95% confidence interval {CI}]: 0.45 [0.29; 0.69]; p = 0.0002), consistent with distant DFS (absolute/relative risk reduction: 3.1/46.3%; HR [95% CI]: 0.52 [0.32; 0.84]; p = 0.0082). The 5-year follow-up confirmed this outcome.Quality of life analyses did not show clinically relevant differences over all time points. Only at month 1, the Functional Assessment of Cancer Therapy - General total score revealed a statistically relevant difference to the disadvantage of neratinib classified as clinically relevant. The tolerability profile of neratinib was dominated by gastrointestinal events, mainly diarrhoea (all grades: 94.4%; grade III: 39.4%; no systematic antidiarrhoeal prophylaxis), nausea (all grades/grade III: 43.9/1.6%), vomiting (26.6/3.2%), abdominal pain (23.8/1.9%), fatigue (28.1/1.9%) and rash (14.3/0.4%). No cumulative or irreversible toxicities were observed. As shown in the CONTROL study and instituted via a risk management plan, diarrhoea management can reduce frequency, cumulative duration and severity of diarrhoea.
Extended adjuvant neratinib provides a clinically relevant benefit with further incremental reduction of relapse risk in the curative setting. Accordingly, the German HTA authority has granted an added benefit for this new treatment option.
奈拉替尼在欧盟被批准用于延长人表皮生长因子受体 2 阳性/激素受体阳性（双阳性）早期乳腺癌的辅助治疗，这些患者在曲妥珠单抗治疗结束后 1 年内完成治疗。在此，我们报告了对德国卫生技术评估（HTA）进行的 ExteNET 试验中激素受体阳性亚组（N=1631）的分析结果。
中位随访 2 年，HTA 分析显示奈拉替尼对比安慰剂在无病生存（DFS）方面具有显著优势（DFS 绝对/相对风险降低：4.1/48.2%；风险比[HR] [95%置信区间{CI}]：0.45 [0.29; 0.69]；p=0.0002），与远处 DFS 一致（DFS 绝对/相对风险降低：3.1/46.3%；HR [95% CI]：0.52 [0.32; 0.84]；p=0.0082）。5 年随访结果证实了这一结果。质量生活分析在所有时间点均未显示出具有临床意义的差异。仅在第 1 个月，功能评估癌症治疗-一般总分显示出对奈拉替尼的统计学相关差异，对奈拉替尼不利，被归类为具有临床意义。奈拉替尼的耐受性特征主要由胃肠道事件引起，主要是腹泻（所有等级：94.4%；等级 III：39.4%；无系统抗腹泻预防）、恶心（所有等级/等级 III：43.9/1.6%）、呕吐（26.6/3.2%）、腹痛（23.8/1.9%）、疲劳（28.1/1.9%）和皮疹（14.3/0.4%）。未观察到累积或不可逆转的毒性。如 CONTROL 研究所示，并通过风险管理计划实施，腹泻管理可降低腹泻的频率、累积持续时间和严重程度。
延长辅助奈拉替尼治疗在治愈性环境中提供了具有临床意义的获益，并进一步降低了复发风险。因此，德国 HTA 机构已为这种新的治疗选择授予了额外的益处。
