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

Area of Science:

• Oncology
• Pharmacology
• Biomarkers

Background:

• Second-line treatment options for advanced gastric cancer (AGC) are limited.
• Lenvatinib, a multi-target tyrosine kinase inhibitor (TKI), combined with paclitaxel, is being explored for AGC.
• Dynamic Network Biomarker (DNB) analysis offers a novel approach to identify predictive biomarkers.

Purpose of the Study:

• Determine the maximum tolerated dose (MTD) of lenvatinib plus paclitaxel in AGC patients.
• Explore molecular biomarkers using DNB analysis for predicting prognosis and treatment response.
• Evaluate the safety and efficacy of this combination therapy.

Main Methods:

• Dose escalation study using a "3 + 3" design for lenvatinib.
• Patients received lenvatinib plus paclitaxel (135 mg/m², q3w).
• DNB analysis was performed on serial blood samples using Olink proteomics data.

Main Results:

• The MTD of lenvatinib was determined to be 16 mg.
• The combination was well-tolerated with a Grade ≥3 adverse event rate of 18.2%.
• Objective response rate was 36.4% with a median overall survival of 7.4 months. A DNBscore was established and associated with prognosis and response.

Conclusions:

• Lenvatinib plus paclitaxel demonstrates promising safety and efficacy as a second-line treatment for AGC.
• The DNBscore shows potential as a predictive biomarker for this combination therapy.
• Further research into DNBs could provide critical insights for targeted therapy in AGC.