Pilot phase II study of the combination of lenvatinib (L) and eribulin (E) in advanced solid tumors.

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.