Department of Medical Oncology, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou, Fujian Province, China.
Fujian Key Laboratory of Translational Cancer Medicine, Fuzhou, Fujian Province, China.
Curr Cancer Drug Targets. 2024;24(5):490-500. doi: 10.2174/0115680096248592231016065117.
This study aimed to observe the efficacy and safety of inetetamab and pyrotinib in combination with vinorelbine in second-line therapy and beyond in HER2-positive metastatic breast cancer (MBC).
Patients with HER2-positive MBC admitted to our hospital from January 2016 to December 2021 were selected. For patients who could not receive antibody‒drug conjugates (ADCs) during second-line (2-line) or third-line and beyond (≥ 3-line) anti-HER2 therapy, inetetamab + pyrotinib + vinorelbine was used for treatment until unacceptable adverse events occurred or the disease progressed, as evaluated by the Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 every 2 cycles. The progression-free survival (PFS), objective response rate (ORR), clinical benefit rate (CBR), and adverse reactions were recorded. Multivariate Cox regression analysis was performed to explore the prognostic factors influencing the curative effect.
Overall, 52 patients were included; 13 patients received 2-line treatment, and 39 patients received ≥ 3-line treatment. The median PFS (mPFS) for all patients treated with inetetamab + pyrotinib + vinorelbine was 7 months. The mPFS of the 2-line subgroup was significantly better than that of the ≥ 3-line subgroup (17 vs. 5 months, P = 0.001). The mPFS of the subgroups that received trastuzumab (H) or trastuzumab and pertuzumab (HP) only was significantly better than that of the H or HP and tyrosine kinase inhibitor (TKI) subgroups (8 vs. 5 months, P = 0.030). The mPFS of the HER2 resistance subgroup was better than that of the HER2 refractoriness subgroup (14 vs. 7 months, P = 0.025). Cox regression analysis showed that the treatment line (2-line more so than ≥ 3-line) was an independent prognostic factor for PFS. In addition, the ORR and CBR of 2-line patients were significantly higher than those of ≥ 3-line patients (69.2% vs. 30.8% and 92.3% vs. 64.1%, respectively). The most common hematological toxicities were leukopenia and neutropenia, and the most common nonhematological toxicity was diarrhea.
Inetetamab and pyrotinib in combination with vinorelbine have good efficacy in ≥ 2-line treatment of HER2-positive MBC with controllable toxicity, and the combination is a new treatment option, especially for patients who cannot use ADCs in 2-line treatment.
本研究旨在观察伊奈妥单抗联合吡咯替尼和长春瑞滨在曲妥珠单抗耐药的 HER2 阳性转移性乳腺癌（MBC）二线及以上治疗中的疗效和安全性。
选取 2016 年 1 月至 2021 年 12 月期间我院收治的 HER2 阳性 MBC 患者。对于二线（2 线）或三线及以上（≥3 线）抗 HER2 治疗中不能使用抗体药物偶联物（ADC）的患者，采用伊奈妥单抗+吡咯替尼+长春瑞滨治疗，直至出现不可接受的不良反应或疾病进展，每 2 个周期根据实体瘤疗效评价标准（RECIST）1.1 进行评估。记录无进展生存期（PFS）、客观缓解率（ORR）、临床获益率（CBR）和不良反应。采用多因素 Cox 回归分析探讨影响疗效的预后因素。
共纳入 52 例患者；13 例患者接受二线治疗，39 例患者接受≥3 线治疗。所有接受伊奈妥单抗+吡咯替尼+长春瑞滨治疗的患者的中位 PFS（mPFS）为 7 个月。二线亚组的 mPFS 明显优于≥3 线亚组（17 比 5 个月，P=0.001）。仅接受曲妥珠单抗（H）或曲妥珠单抗和帕妥珠单抗（HP）治疗的亚组 mPFS 明显优于 H 或 HP 和酪氨酸激酶抑制剂（TKI）治疗的亚组（8 比 5 个月，P=0.030）。HER2 耐药亚组的 mPFS 优于 HER2 抵抗亚组（14 比 7 个月，P=0.025）。Cox 回归分析显示，治疗线（二线优于≥3 线）是 PFS 的独立预后因素。此外，二线患者的 ORR 和 CBR 明显高于≥3 线患者（69.2%比 30.8%和 92.3%比 64.1%）。最常见的血液学毒性是白细胞减少和中性粒细胞减少，最常见的非血液学毒性是腹泻。
伊奈妥单抗联合吡咯替尼和长春瑞滨在曲妥珠单抗耐药的 HER2 阳性 MBC 的≥2 线治疗中具有良好的疗效，且毒性可控制，是一种新的治疗选择，尤其适用于二线治疗中不能使用 ADC 的患者。
