Lenvatinib Plus Paclitaxel as Second‐Line Therapy for Advanced Gastric Cancer Patients: A Dose Escalation Exploratory Study

Second‐line treatment options for advanced gastric cancer (AGC) patients remain limited. This dose escalation exploratory study is aimed to determine the maximum tolerated dose (MTD) of lenvatinib plus paclitaxel as second‐line treatment in AGC and to explore molecular biomarkers using dynamic network biomarker (DNB) analysis. Eligible patients are treated with lenvatinib plus paclitaxel (135 mg m⁻², q3w). Dose escalation of lenvatinib adopts a “3 + 3” design. DNB analysis is performed based on Olink proteomics data using serial blood samples. Eleven patients are treated. No dose‐limiting toxicities are observed, and the MTD of lenvatinib is determined as 16 mg. White blood cells decreased (45.5%, 5/11) is the most common adverse event. Grade ≥3 adverse event rate is 18.2% (2/11). Objective response rate is 36.4% (4/11), and median overall survival is 7.4 months. A DNBscore associated with patient prognosis and response to multitarget tyrosine kinase inhibitor (TKI) plus paclitaxel is established. Infiltration of cancer‐associated fibroblasts in tumor microenvironment is positively associated with the DNBscore. In summary, lenvatinib plus paclitaxel is well tolerant and shows promising efficacy as a second‐line regimen in AGC. The DNBscore can be a biomarker for multitarget TKI plus paclitaxel and provide critical clues for future research .