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

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. 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. 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. 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.