Purpose: Accumulating toxicities hinder indefinite chemotherapy for many patients with metastatic/recurrent HER2-negative breast cancer. We conducted a phase II trial of pembrolizumab monotherapy following induction chemotherapy to determine the efficacy of maintenance immunotherapy in patients with metastatic HER2-negative inflammatory breast cancer (IBC) and non-IBC triple-negative breast cancer (TNBC) and a biomarker study. Patients and Methods: Patients with a complete response (CR), partial response (PR), or stable disease (SD) after at least 3 cycles of chemotherapy for HER2-negative breast cancer received pembrolizumab, regardless of programmed death-ligand 1 expression. Pembrolizumab (200 mg) was administered every 3 weeks until disease progression, intolerable toxicity, or 2 years of pembrolizumab exposure. The endpoints included the 4-month disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and response biomarkers in the blood. Results: Of 43 treated patients, 11 had metastatic IBC and 32 non-IBC TNBC. The 4-month DCR was 58.1% (95% CI, 43.4%-72.9%). For all patients, the median PFS was 4.8 months (95% CI, 3.0-7.1 months). The toxicity profile was similar to the previous pembrolizumab monotherapy study. Patients with high T-cell clonality at baseline had a longer PFS with pembrolizumab treatment than did those with low T-cell clonality (10.4 vs. 3.6 months, p = 0.04). Patients who achieved SD also demonstrated a significant increase in T-cell clonality during therapy compared to those who didn't achieve SD (20% vs. 5.9% mean increase, respectively; p = 0.04). Conclusions: Pembrolizumab monotherapy achieved durable treatment responses. Patients with a high baseline T-cell clonality had prolonged disease control with pembrolizumab.

中文翻译：

---

先前对化疗有反应的转移性 HER2 阴性乳腺癌患者的维持帕博利珠单抗治疗

目的：累积的毒性阻碍了许多转移性/复发性 HER2 阴性乳腺癌患者的无限期化疗。我们在诱导化疗后进行了派姆单抗单药治疗的 II 期试验，以确定维持免疫治疗对转移性 HER2 阴性炎症性乳腺癌 (IBC) 和非 IBC 三阴性乳腺癌 (TNBC) 患者的疗效以及生物标志物研究。患者和方法：在 HER2 阴性乳腺癌化疗至少 3 个周期后达到完全缓解 (CR)、部分缓解 (PR) 或疾病稳定 (SD) 的患者接受派姆单抗治疗，无论程序性死亡配体 1 的表达如何。每 3 周给予一次 Pembrolizumab（200 mg），直至疾病进展、出现无法耐受的毒性或暴露于 Pembrolizumab 2 年。终点包括 4 个月疾病控制率 (DCR)、无进展生存期 (PFS)、总生存期 (OS) 和血液中的反应生物标志物。结果：43 名接受治疗的患者中，11 名患有转移性 IBC，32 名患有非 IBC TNBC。 4 个月 DCR 为 58.1%（95% CI，43.4%-72.9%）。对于所有患者，中位 PFS 为 4.8 个月（95% CI，3.0-7.1 个月）。毒性特征与之前的派姆单抗单药治疗研究相似。基线时 T 细胞克隆度高的患者在接受派姆单抗治疗后的 PFS 比 T 细胞克隆度低的患者更长（10.4 个月与 3.6 个月，p = 0.04）。与未实现 SD 的患者相比，实现 SD 的患者在治疗期间 T 细胞克隆性也显着增加（分别平均增加 20% 和 5.9%；p = 0.04）。结论：派姆单抗单一疗法取得了持久的治疗反应。具有高基线 T 细胞克隆性的患者使用派姆单抗可延长疾病控制时间。