A Randomized, Multi-Center, Open Label Study to Compare the Safety and Efficacy between Afatinib Monotherapy and Combination Therapy with HAD-B1 for the Locally Advanced or Metastatic NSCLC Patients with EGFR Mutations

Background: Lung cancer, especially non-small cell lung cancer (NSCLC), poses a significant health challenge globally due to its high mortality. Afatinib, a second-generation epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI), has shown superior efficacy over traditional chemotherapy in NSCLC treatment. However, issues like secondary resistance and adverse effects call for alternative therapies. HAD-B1, comprising 4 herbal medicines, has shown promise in lung cancer treatment in both preclinical and clinical settings. This study assesses the combination of HAD-B1 and Afatinib in advanced NSCLC patients to potentially improve outcomes by addressing the limitations of current EGFR-TKI therapies.Method: A randomized, open-label trial evaluated the efficacy and safety of HAD-B1 with Afatinib in 90 EGFR-mutation-positive NSCLC patients. Participants were divided into treatment and control groups, receiving Afatinib with or without HAD-B1. The study focused on the initial dose maintenance rate and disease control rate (DCR) of Afatinib, alongside secondary outcomes like survival rates and quality of life, under continuous safety monitoring.Results: Among the 90 participants, no significant difference was found in initial dose maintenance (60.98% in the treatment group vs 52.50% in the control, P = .4414) or DCR (80.49% vs 90.00%, P = .2283). Secondary outcomes like PFS, TTP, and OS showed no notable differences. However, physical functioning significantly improved in the treatment group (P = .0475, PPS group). The control group experienced higher rates of adverse events of special interest and adverse drug reactions (P = .01), suggesting HAD-B1 with Afatinib might enhance physical function without increasing adverse effects.Conclusion: Combining HAD-B1 with Afatinib potentially improves quality of life and reduces adverse events in advanced NSCLC patients. Further research is necessary to confirm the long-term benefits of this combination therapy, aiming to advance NSCLC treatment outcomes.Trial registration: Clinical Research Information Service (CRIS) of the Republic of Korea, https://cris.nih.go.kr/ (ID: KCT0005414).