ImportanceThe potential benefit of combining intracranial effective systemic therapy with radiotherapy for patients with breast cancer with brain metastases remains unclear.ObjectiveTo assess the activity and safety of combining radiotherapy with pyrotinib and capecitabine in patients with ERBB2-positive breast cancer and brain metastases.Design, Setting, and ParticipantsThis was a single-arm, single-center, phase 2 nonrandomized clinical trial with a safety run-in phase. Between January 2020 and August 2022, patients with ERBB2-positive breast cancer and brain metastases were enrolled. The data cutoff date was February 1, 2023.InterventionsPatients received either fractionated stereotactic radiotherapy or whole-brain radiotherapy. Treatment with pyrotinib (400 mg, once daily) and capecitabine (1000 mg/m2, twice daily, on days 1-14 of each 21-day cycle) was initiated from the first day of radiotherapy to the seventh day after the completion of radiotherapy and continued until disease progression or unacceptable toxic effects.Main Outcomes and MeasuresThe primary end point was 1-year central nervous system (CNS) progression-free survival (PFS) rate. Secondary end points included CNS objective response rate (ORR), PFS, overall survival (OS), safety, and changes in neurocognitive function.ResultsA total of 40 female patients (median age, 50.5 years [IQR, 46-59 years]) were enrolled and received treatment, including 3 patients in safety run-in phase. With a median follow-up of 17.3 months (IQR, 10.3-26.9), the 1-year CNS PFS rate was 74.9% (95% CI, 61.9%-90.7%), and the median CNS PFS was 18.0 months (95% CI, 15.5 to not reached). The 1-year PFS rate was 66.9% (95% CI, 53.1%-84.2%), and the median PFS was 17.6 months (95% CI, 12.8-34.1). The CNS objective response rate was 85% (34 of 40). Median overall survival was not reached. The most common grade 3 or 4 treatment-related adverse event was diarrhea (7.5%). Asymptomatic radiation necrosis was identified in 4 of 67 lesions (6.0%) treated with fractionated stereotactic radiotherapy. Most patients maintained neurocognitive function, as evaluated by the Mini-Mental State Examination at different points.Conclusions and RelevanceThe results of this trial suggest that radiotherapy combined with pyrotinib and capecitabine is associated with long intracranial survival benefit in patients with ERBB2-positive advanced breast cancer and brain metastases with an acceptable safety profile. This combination deserves further validation.Trial RegistrationClinicalTrials.gov Identifier: NCT04582968

中文翻译：

---

吡咯替尼和卡培他滨对 ERBB2 阳性晚期乳腺癌和脑转移患者的脑部放疗

重要性颅内有效全身治疗与放疗相结合对乳腺癌脑转移患者的潜在益处尚不清楚。目的评估放疗联合吡咯替尼和卡培他滨治疗乳腺癌脑转移患者的活性和安全性。ERBB2-阳性乳腺癌和脑转移。设计、设置和参与者这是一项单臂、单中心、2 期非随机临床试验，具有安全磨合期。2020 年 1 月至 2022 年 8 月期间，患有以下疾病的患者ERBB2-阳性乳腺癌和脑转移患者被纳入。数据截止日期为 2023 年 2 月 1 日。 干预措施患者接受分段立体定向放射治疗或全脑放射治疗。使用吡咯替尼（400 mg，每日一次）和卡培他滨（1000 mg/m2，每天两次，每个21天周期的第1-14天）从放疗第一天开始到放疗完成后第七天，一直持续到疾病进展或不可接受的毒性作用。 主要终点和措施主要终点是1年中枢神经系统（CNS）无进展生存（PFS）率。次要终点包括中枢神经系统客观缓解率 (ORR)、PFS、总生存期 (OS)、安全性和神经认知功能变化。 结果 共有 40 名女性患者（中位年龄，50.5 岁 [IQR，46-59 岁]）进行了研究入组并接受治疗，其中3名患者处于安全磨合期。中位随访时间为 17.3 个月（IQR，10.3-26.9），1 年 CNS PFS 率为 74.9%（95% CI，61.9%-90.7%），中位 CNS PFS 为 18.0 个月（95% CI，15.5 至未达到）。1 年 PFS 率为 66.9%（95% CI，53.1%-84.2%），中位 PFS 为 17.6 个月（95% CI，12.8-34.1）。CNS 客观缓解率为 85%（40 例中有 34 例）。未达到中位总生存期。最常见的 3 级或 4 级治疗相关不良事件是腹泻（7.5%）。在接受分割立体定向放射治疗的 67 个病灶中，有 4 个（6.0%）发现无症状放射性坏死。根据不同点的简易精神状态检查的评估，大多数患者保持了神经认知功能。结论和相关性该试验的结果表明，放疗联合吡咯替尼和卡培他滨与患有以下疾病的患者的长期颅内生存获益相关：ERBB2-具有可接受的安全性的阳性晚期乳腺癌和脑转移瘤。该组合值得进一步验证。试验注册ClinicalTrials.gov 标识符：NCT04582968