Banwait Ranjit, Ko Heidi, Michalek Joel, Liu Qianqian, Lathrop Kate, Bowhay-Carnes Elizabeth, Fotopoulos Georgios, Sarantopoulos John, Elledge Richard, Taverna Josephine, Karnad Anand, Siziopikou Kalliopi P, Kaklamani Virginia
Department of Medicine, Division of Hematology Oncology, UT Health San Antonio, Mays Cancer Center, San Antonio, Texas, USA.
Biostatistics Division, Department of Population Health Sciences, UT Health San Antonio, San Antonio, Texas, USA.
Int J Cancer. 2025 Aug 15;157(4):752-759. doi: 10.1002/ijc.35446. Epub 2025 Apr 15.
This pilot phase II study evaluated the combination of lenvatinib, a multi-kinase inhibitor, and eribulin, a microtubule inhibitor, in patients with advanced solid tumors, including breast carcinoma, lung carcinoma, and sarcoma. Tumor angiogenesis and resistance mechanisms to anti-angiogenic therapies were primary motivations for combining these agents. The trial enrolled 29 patients, heavily pretreated with at least three prior lines of chemotherapy, and aimed to assess the efficacy and safety of the combination therapy. Overall response rate (ORR) was 24% with the highest responses observed in breast cancer (29%) and lung cancer (33%) patients. Median progression-free survival (PFS) was 7.4 months (95% CI 4.5, NA), and overall survival (OS) was 8.2 months (95% CI 6.4 to 14.9). A significant improvement in both OS and PFS was found in vimentin-negative patients, suggesting that vimentin expression may be a predictor of treatment response. The most common treatment-related adverse events (TRAEs) were oral mucositis, fatigue, neutropenia, and nausea. Grade ≥3 TRAEs included neutropenia (34.5%), febrile neutropenia (17.2%), and hypertension (13.8%), with one fatal case of sepsis reported. While the study demonstrated the potential of lenvatinib and eribulin in advanced solid tumors, particularly breast and lung cancers, it also highlighted the need for further investigation into biomarkers like vimentin to predict therapeutic outcomes. The combination therapy was manageable in terms of safety and toxicity, with a predictable safety profile. These findings suggest that lenvatinib and eribulin represent a promising treatment strategy for advanced, heavily pretreated solid tumors, warranting further exploration in larger clinical studies.
这项II期试点研究评估了多激酶抑制剂乐伐替尼与微管抑制剂艾日布林联合用于晚期实体瘤患者（包括乳腺癌、肺癌和肉瘤）的疗效。肿瘤血管生成以及对抗血管生成疗法的耐药机制是联合使用这些药物的主要动机。该试验纳入了29例至少接受过三线化疗的患者，旨在评估联合治疗的疗效和安全性。总体缓解率（ORR）为24%，其中乳腺癌患者（29%）和肺癌患者（33%）的缓解率最高。中位无进展生存期（PFS）为7.4个月（95%CI 4.5，NA），总生存期（OS）为8.2个月（95%CI 6.4至14.9）。波形蛋白阴性患者的OS和PFS均有显著改善，这表明波形蛋白表达可能是治疗反应的一个预测指标。最常见的治疗相关不良事件（TRAEs）为口腔黏膜炎、疲劳、中性粒细胞减少和恶心。≥3级TRAEs包括中性粒细胞减少（34.5%）、发热性中性粒细胞减少（17.2%）和高血压（13.8%），报告了1例败血症死亡病例。虽然该研究证明了乐伐替尼和艾日布林在晚期实体瘤（尤其是乳腺癌和肺癌）中的潜力，但也强调了需要进一步研究波形蛋白等生物标志物以预测治疗结果。联合治疗在安全性和毒性方面是可控的，具有可预测的安全性。这些发现表明，乐伐替尼和艾日布林是晚期、经过大量预处理的实体瘤的一种有前景的治疗策略，值得在更大规模的临床研究中进一步探索。
