# Model-Based Evaluation of HangAmDan-B1 and Afatinib Combination Therapy in HCC827 Xenograft Mice with Resistance to Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor

## TL;DR

This study uses a model to show that combining a herbal mixture with afatinib improves treatment of resistant lung cancer in mice.

## Contribution

A pharmacokinetic/pharmacodynamic model quantifies the synergy between HAD-B1 and afatinib in resistant lung cancer.

## Key findings

- HAD-B1 increases the potency of afatinib by 1.45-fold in resistant tumor models.
- Combination therapy maintains smaller tumor sizes compared to afatinib alone.
- The model provides insights for optimizing dosing strategies in resistant NSCLC.

## Abstract

Objectives: HangAmDan-B1 (HAD-B1), a blended herbal mixture, has been investigated as an adjuvant therapy with afatinib (AFT) to treat non-small lung cancer (NSCLC). Although preclinical studies demonstrated promising synergistic results, clinical trials have not yet confirmed the expected benefits. This study aims to quantitatively examine the exposure–response relationship and synergistic interactions through pharmacokinetic/pharmacodynamic (PK/PD) modeling. Methods: A PK/PD model was established and validated based on tumor growth profiles from a xenograft mouse study of gefitinib-resistant HCC827. Model-based simulations were performed to predict and assess therapeutic effects across different treatment groups. Results: The PK/PD model confirmed HAD-B1 enhances the potency of AFT by 1.45-fold. Model-based simulations predicted that combination treatment maintains a lower tumor size compared to AFT monotherapy. Conclusions: This study quantitatively demonstrated the synergistic interaction between HAD-B1 and AFT. The developed PK/PD model provides insights into potential dosing strategies to treat NSCLC resistant to EGFR-TKIs. Further clinical trials are warranted to validate these findings and refine dosing strategies to improve therapeutic outcomes.