HER2 阳性乳腺癌脑转移患者几乎没有有效的全身治疗选择。在之前的一项研究中，帕妥珠单抗与大剂量曲妥珠单抗在脑转移患者的中枢神经系统（CNS）中表现出较高的临床获益率（CBR）。目前的试验评估了在该方案中添加atezolizumab是否会进一步改善CNS反应。这是一项针对HER2阳性患者的atezolizumab、帕妥珠单抗和大剂量曲妥珠单抗的单臂、多中心、II期试验乳腺癌脑转移。参与者每 3 周接受 1200 mg IV 治疗（每 3 周一次）、帕妥珠单抗（负荷剂量 840 mg IV，然后每 3 周一次 420 mg IV）和高剂量曲妥珠单抗（每周 6 mg/kg IV，持续 24 周，然后 6 mg/kg IV） q3w）。主要终点是根据神经肿瘤脑转移反应评估 (RANO-BM) 标准的中枢神经系统总体缓解率 (ORR)。关键的次要终点包括 CBR、总生存期 (OS) 以及组合的安全性和耐受性。 在 19 名入组参与者中，两人的 CNS-ORR 确认颅内部分缓解为 10.5%（90% CI：1.9%-29.6%） ）。该研究未达到预先设定的疗效阈值并提前终止。 18 周时的 CBR 为 42.1%，24 周时的 CBR 为 31.6%。 7 名患者 (36.8%) 需要延迟或暂停剂量，最常见的任何级别不良事件是腹泻 (26.3%) 和疲劳 (26.3%)。在帕妥珠单抗加高剂量曲妥珠单抗中添加阿替利珠单抗不会导致改善 HER2 阳性乳腺癌脑转移患者的中枢神经系统反应。

Patients with HER2-positive breast cancer brain metastases have few effective systemic therapy options. In a prior study, pertuzumab with high-dose trastuzumab demonstrated a high clinical benefit rate (CBR) in the central nervous system (CNS) in patients with brain metastases. The current trial evaluated whether the addition of atezolizumab to this regimen would produce further improvements in CNS response.This was a single-arm, multi-center, phase II trial of atezolizumab, pertuzumab, and high-dose trastuzumab for patients with HER2-positive breast cancer brain metastases. Participants received atezolizumab 1200 mg IV every 3 weeks (q3w), pertuzumab (loading dose 840 mg IV, then 420 mg IV q3w), and high-dose trastuzumab (6 mg/kg IV weekly for 24 weeks, then 6 mg/kg IV q3w). The primary endpoint was CNS overall response rate (ORR) per Response Assessment in Neuro-Oncology Brain Metastases (RANO-BM) criteria. Key secondary endpoints included CBR, overall survival (OS), and safety and tolerability of the combination.Among 19 enrolled participants, two had a confirmed intracranial partial response for a CNS-ORR of 10.5% (90% CI: 1.9%-29.6%). The study did not meet the prespecified efficacy threshold and was terminated early. The CBR was 42.1% at 18 weeks and 31.6% at 24 weeks. Seven patients (36.8%) required a dose delay or hold, and the most frequent any-grade adverse events were diarrhea (26.3%) and fatigue (26.3%).The addition of atezolizumab to pertuzumab plus high-dose trastuzumab does not result in improved CNS responses in patients with HER2-positive breast cancer brain metastases.