The PATRICIA study (NCT02536339) examined the efficacy and safety of pertuzumab plus high-dose trastuzumab in patients with HER2-positive metastatic breast cancer (MBC) with progressive central nervous system (CNS) metastases following radiotherapy. Primary analysis confirmed CNS objective response rate (ORR) was 11% (95% confidence interval [CI]: 3–25); clinical benefit rate (CBR) was 68% (4 months) and 51% (6 months). We report final efficacy data after a further 21-months of follow-up, updated safety, survival, and patient-reported outcomes (PROs). Patients received standard-dose pertuzumab plus high-dose trastuzumab (6 mg/kg weekly) until CNS or systemic disease progression or unacceptable toxicity. Primary endpoint: confirmed ORR (CNS) per Response Assessment in Neuro-Oncology Brain Metastases criteria. Secondary endpoints were response duration, CBR, progression-free survival (PFS), overall survival (OS), safety, and PROs. By clinical cut-off, 39 patients had completed or discontinued treatment. Confirmed ORR (CNS) was 11% (95% CI: 3.0–25.4). Median CNS-PFS was 4.6 months (95% CI: 4.0–8.9), as was median CNS-PFS or systemic PFS (95% CI: 4.0–8.9); median OS was 27.2 months (95% CI: 16.1–not reached). CBR in the CNS was 51% (19 patients, 95% CI: 34.4–68.1) at 6 months. Two patients remained on treatment until study closure, achieving stable disease for 4.1 and 4.8 years. Treatment-related grade 3/4 adverse events occurred in 7.7% of patients. Patients with confirmed partial response or stable disease (≥4 months) in the CNS had stable PROs over time. Pertuzumab plus high-dose trastuzumab represents a reasonable non-chemotherapeutic treatment option for selected patients with HER2-positive MBC with CNS metastases.

PATRICIA 研究 (NCT02536339) 检查了帕妥珠单抗联合高剂量曲妥珠单抗治疗放疗后出现进展性中枢神经系统 (CNS) 转移的 HER2 阳性转移性乳腺癌 (MBC) 患者的疗效和安全性。初步分析证实 CNS 客观缓解率 (ORR) 为 11%（95% 置信区间 [CI]：3-25）；临床获益率（CBR）分别为68%（4个月）和51%（6个月）。我们在经过 21 个月的随访、更新的安全性、生存率和患者报告结果 (PRO) 后报告最终疗效数据。患者接受标准剂量帕妥珠单抗加高剂量曲妥珠单抗（每周 6 mg/kg），直至中枢神经系统或全身疾病进展或出现不可接受的毒性。主要终点：根据神经肿瘤脑转移标准中的反应评估确认 ORR (CNS)。次要终点是缓解持续时间、CBR、无进展生存期 (PFS)、总生存期 (OS)、安全性和 PRO。截至临床截止，39 名患者已完成或停止治疗。确认的 ORR (CNS) 为 11% (95% CI: 3.0–25.4)。中位 CNS-PFS 为 4.6 个月（95% CI：4.0-8.9），中位 CNS-PFS 或全身性 PFS 也为 4.6 个月（95% CI：4.0-8.9）；中位 OS 为 27.2 个月（95% CI：16.1 – 未达到）。6 个月时 CNS 的 CBR 为 51%（19 名患者，95% CI：34.4–68.1）。两名患者继续接受治疗直至研究结束，分别达到疾病稳定 4.1 和 4.8 年。7.7% 的患者发生了与治疗相关的 3/4 级不良事件。经确认中枢神经系统部分缓解或疾病稳定（≥4 个月）的患者随着时间的推移具有稳定的 PRO。对于选定的患有 CNS 转移的 HER2 阳性 MBC 患者来说，帕妥珠单抗联合高剂量曲妥珠单抗是一种合理的非化疗治疗选择。