保乳术后 HER2 阳性导管原位癌接受放疗与放化疗对比的 III 期临床试验
Comparison of Radiation With or Without Concurrent Trastuzumab for HER2-Positive Ductal Carcinoma In Situ Resected by Lumpectomy: A Phase III Clinical Trial.
机构信息
NRG Oncology, Pittsburgh, PA.
Rush University Medical Center, Chicago, IL.
出版信息
J Clin Oncol. 2021 Jul 20;39(21):2367-2374. doi: 10.1200/JCO.20.02824. Epub 2021 Mar 19.
PURPOSE
Preclinical studies report that trastuzumab (T) can boost radiotherapy (RT) effectiveness. The primary aim of the B-43 trial was to assess the efficacy of RT alone vs concurrent RT plus T in preventing recurrence of ipsilateral breast cancer (IBTR) in women with ductal carcinoma in situ (DCIS).
PATIENTS AND METHODS
Eligibility: Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1, DCIS resected by lumpectomy, known estrogen receptor (ER) and/or progesterone receptor (PgR), and human epidermal growth factor receptor 2 (HER2) status by centralized testing. Whole-breast RT was given concurrently with T. Stratification was by menopausal status, adjuvant endocrine therapy plan, and nuclear grade. Definitive intent-to-treat primary analysis was to be conducted when either 163 IBTR events occurred or all accrued patients were on study ≥ 5 years.
RESULTS
There were 2,014 participants who were randomly assigned. Median follow-up time as of December 31, 2019, was 79.2 months. At primary definitive analysis, 114 IBTR events occurred: RT arm, 63 and RT plus T arm, 51 (hazard ratio [HR], 0.81; 95% CI, 0.56 to 1.17; value = .26). There were 34 who were invasive: RT arm, 18 and RT plus T arm, 20 (HR, 1.11; 95% CI, 0.59 to 2.10; value = .71). Seventy-six were DCIS: RT arm, 45 and RT plus T arm, 31 (HR, 0.68; 95% CI, 0.43 to 1.08; value = .11). Annual IBTR event rates were: RT arm, 0.99%/y and RT plus T arm, 0.79%/y. The study did not reach the 163 protocol-specified events, so the definitive analysis was triggered by all patients having been on study for ≥ 5 years.
CONCLUSION
Addition of T to RT did not achieve the objective of 36% reduction in IBTR rate but did achieve a modest but statistically nonsignificant reduction of 19%. Nonetheless, this trial had negative results. Further exploration of RT plus T is needed in HER2-positive DCIS before its routine delivery in patients with DCIS resected by lumpectomy.
目的
临床前研究报告曲妥珠单抗（T）可增强放射治疗（RT）的效果。B-43 试验的主要目的是评估单独 RT 与同步 RT 加 T 预防导管原位癌（DCIS）患者同侧乳腺癌（IBTR）复发的疗效。
患者和方法
入选标准：东部肿瘤协作组（ECOG）体能状态 0 或 1，经保乳切除术切除的 DCIS，已知雌激素受体（ER）和/或孕激素受体（PgR），以及人表皮生长因子受体 2（HER2）状态通过集中检测。全乳 RT 与 T 同步进行。分层因素为绝经状态、辅助内分泌治疗方案和核分级。当 163 例 IBTR 事件发生或所有入组患者研究时间≥5 年时，进行确定性意向治疗的主要分析。
结果
共有 2014 名患者被随机分配。截至 2019 年 12 月 31 日，中位随访时间为 79.2 个月。在主要的确定性分析中，发生了 114 例 IBTR 事件：RT 组 63 例，RT 加 T 组 51 例（风险比[HR]，0.81；95%CI，0.56 至 1.17；值=.26）。有 34 例为浸润性：RT 组 18 例，RT 加 T 组 20 例（HR，1.11；95%CI，0.59 至 2.10；值=.71）。76 例为 DCIS：RT 组 45 例，RT 加 T 组 31 例（HR，0.68；95%CI，0.43 至 1.08；值=.11）。每年 IBTR 事件发生率为：RT 组 0.99%/年，RT 加 T 组 0.79%/年。该研究未达到方案规定的 163 例事件，因此所有患者的研究时间≥5 年触发了确定性分析。
结论
在 RT 中加入 T 并没有达到降低 IBTR 率 36%的目标，但确实降低了 19%，尽管幅度较小，但无统计学意义。尽管如此，该试验结果为阴性。在接受保乳切除术的 DCIS 患者中，在常规应用于 DCIS 患者之前，需要进一步探索 HER2 阳性 DCIS 中 RT 加 T 的应用。
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