伊奈他单抗联合吡罗替尼和口服长春瑞滨治疗人类表皮生长因子受体 2 阳性晚期乳腺癌患者：单臂 2 期临床试验

Cancer pathogenesis and therapy Pub Date : 2024-01-01 DOI:10.1016/j.cpt.2023.10.004

Nan Jin , Yi Xu , Siqi Wang , Chunxiao Sun , Xueqi Yan , Fan Yang , Yan Liang , Weiwei Chen , Xiang Huang

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引用次数: 0

摘要

背景人类表皮生长因子受体2（HER2）靶向药物已显著改善了HER2阳性乳腺癌患者的预后；然而，仍有很大一部分患者对曲妥珠单抗产生了耐药性。本研究探讨了伊奈他单抗（另一种抗HER2抗体）联合吡罗替尼和口服长春瑞滨治疗HER2阳性晚期乳腺癌患者的疗效和安全性，以期为治疗提供新思路。方法在这项前瞻性、单臂、2期试验中，招募了曲妥珠单抗治疗后疾病进展的HER2阳性晚期乳腺癌患者。患者接受伊奈他单抗（负荷剂量为8毫克/千克，随后每3周静脉注射一次，剂量为6毫克/千克）、吡罗替尼（400毫克，口服，每天一次）和长春瑞滨（60毫克/平方米，口服，每周一次）的联合治疗，直至疾病进展或出现不可耐受的毒性反应。主要终点是无进展生存期（PFS）。次要终点包括客观反应率（ORR）、总生存率（OS）、疾病控制率（DCR）和安全性。结果2022年2月13日至2022年12月25日期间，本研究共筛选并招募了30名患者。入组患者的中位年龄为54岁，12名患者（40.0%）激素受体阳性，23名患者（76.7%）有内脏转移。中位生存期为8.63个月（95%置信区间[CI] 4.15-13.12个月）。未达到中位OS。ORR为53.3%（16/30），DCR为96.7%（29/30）。最常见的III/IV级不良事件为白细胞减少（5例，16.7%）、中性粒细胞减少（4例，13.3%）和腹泻（3例，10%）。结论伊奈他单抗、吡罗替尼和口服长春瑞滨的联合治疗方案在HER2阳性晚期乳腺癌患者中显示出令人鼓舞的疗效和良好的安全性，可作为患者的另一种治疗选择。试验登记号：NCT05823623；https://www.clinicaltrials.gov/。

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Inetetamab combined with pyrotinib and oral vinorelbine for patients with human epidermal growth factor receptor 2 positive advanced breast cancer: A single-arm phase 2 clinical trial

Background

Human epidermal growth factor receptor 2 (HER2)-targeted agents have significantly improved the outcomes of patients with HER2-positive breast cancer; however, a large proportion of patients still develop resistance to trastuzumab. In this study, we investigated the efficacy and safety of inetetamab, another anti-HER2 antibody, combined with pyrotinib and oral vinorelbine in patients with HER2-positive advanced breast cancer so as to provide new ideas for the treatment.

Methods

In this prospective, single-arm, phase 2 trial, patients with HER2-positive advanced breast cancer with disease progression after trastuzumab were recruited. Patients received a combination of inetetamab (loading dose of 8 mg/kg and subsequent doses of 6 mg/kg intravenously once every 3 weeks), pyrotinib (400 mg orally once daily), and vinorelbine (60 mg/m² orally once weekly) until disease progression or intolerable toxicity. The primary endpoint was progression-free survival (PFS). The secondary endpoints included objective response rate (ORR), overall survival (OS), disease control rate (DCR), and safety.

Results

Between February 13, 2022 and December 25, 2022, 30 patients were screened and enrolled in this study. The median age of the patients at enrollment was 54 years, 12 patients (40.0 %) had hormone-receptor-positive disease and 23 patients (76.7 %) had visceral metastasis. The median PFS was 8.63 months (95 % confidence interval [CI] 4.15–13.12 months). The median OS was not reached. The ORR was 53.3 % (16/30) and the DCR was 96.7 % (29/30). The most common Grade III/IV adverse events were leukopenia (n = 5, 16.7 %), neutropenia (n = 4, 13.3 %), and diarrhea (n = 3, 10 %). No treatment-related serious adverse events or deaths occurred.

Conclusions

The combination regimen of inetetamab, pyrotinib, and oral vinorelbine showed encouraging efficacy and favorable safety in patients with HER2-positive advanced breast cancer and could be considered as an alternative treatment option for the patients.