Efficacy and Safety of Almonertinib Combined With Recombinant Human Endostatin in the Treatment of Stage IIIB-IV Non-small Cell Lung Cancer

Rationale:

Non-small cell lung cancer (NSCLC) is the most common type of lung cancer in the world, and patients with stage IIIB-IV have a poor prognosis. EGFR mutations, especially the 19th amino acid deletion (19del) and the 21st amino acid L858R mutation, are the most common types of gene mutations in NSCLC. These mutations usually lead to overactivity of EGFR, thereby stimulating excessive proliferation of lung cancer cells. At present, the conventional treatment for such patients is mainly the use of EGFR tyrosine kinase inhibitors (EGFR-TKIs) for treatment. However, although EGFR-TKIs have achieved certain results in the treatment of NSCLC patients with EGFR mutations, their treatment effects are often difficult to sustain due to the resistance of patients to these drugs. Therefore, finding new treatment strategies to improve the survival rate and quality of life of such patients is an important current research direction. The results of many studies suggest that EGFR TKIs and anti-angiogenic drugs can inhibit tumors from different signaling pathways. EGFR-TKIs can inhibit the epidermal growth factor receptor pathway and inhibit tumor growth; anti-angiogenic drugs inhibit tumor angiogenesis by binding to vascular endothelial growth factor (VEGF). At the same time, the combination of the two has a synergistic effect. Both EGFR and VEGFR-2 signaling pathways can trigger downstream signaling pathways such as PI3K/AKT and RAS/RAF/ERK, affecting cell proliferation. EGFR activation can also drive HIF-1α upregulation, leading to VEGF gene expression. Many clinical studies have confirmed that the A+T treatment model can improve the efficacy of EGFR-positive NSCLC.

Methods:

This study is planned to adopt a mixed design. We will prospectively collect new patient data and retrospectively analyze existing patient data. In the prospective part, we will treat patients with stage IIIB-IV NSCLC with EGFR amino acid 21 L858R mutation and amino acid 19 deletion (19del) with a combination of ametinib mesylate (AUMOLERTINIB) and recombinant human endostatin (ENDOSTAR). In the retrospective part, we will extract the existing data of patients treated with AUMOLERTINIB alone from the hospital\'s electronic medical record system as a control group. The primary endpoint is progression free survival (PFS). Secondary endpoints are objective response rate (ORR), duration of response (DoR), adverse events (AE), quality of life (EORTCQLQ-L13) score, anxiety and depression self-rating scale (HADS) and patient health questionnaire-9 (PHQ-9).

Route:

In the prospective part, we will perform genetic testing on patients to determine their EGFR mutation status. Then, we will treat patients with stage IIIB-IV NSCLC with EGFR amino acid 21 L858R mutation and amino acid 19 deletion with ametinib mesylate and recombinant human endostatin, and match the corresponding data in the hospital database. We will regularly follow up patients participating in the prospective study, collect data on their disease progression and survival, and perform statistical analysis on these data to evaluate the effectiveness and safety of the combination therapy.

Expected:

We expect that the combination of ametinib mesylate and recombinant human endostatin can improve the survival rate and quality of life of patients with stage IIIB-IV NSCLC with EGFR amino acid 21 L858R mutation and amino acid 19 deletion. This is mainly because ametinib mesylate and recombinant human endostatin target EGFR hyperactivity and angiogenesis, two processes that play a key role in the development of NSCLC, respectively, so their combined use may produce a synergistic effect, thereby improving the therapeutic effect.