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

## TL;DR

This study explores a new treatment for advanced gastric cancer using lenvatinib and paclitaxel, finding it safe and effective with a promising biomarker panel.

## Contribution

The study identifies a safe dose of lenvatinib with paclitaxel and introduces a dynamic network biomarker for prognosis and treatment response.

## Key findings

- Lenvatinib plus paclitaxel is well tolerated with a maximum tolerated dose of 16 mg.
- A dynamic network biomarker (DNBscore) is linked to prognosis and treatment response.
- Infiltration of cancer-associated fibroblasts correlates with the DNBscore.

## Abstract

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 .

This study determines the maximum tolerated dose of lenvatinib in combination with paclitaxel as second‐line therapy for advanced gastric cancer patients. A dynamic network biomarker panel associated with patient prognosis and response to treatment is established. The finding provides information for patient enrichment and new target selection in future clinical trials of angiogenesis inhibitor‐based treatment in gastric cancer.