high-dose furmonertinib combined with bevacizumab and intrathecal pemetrexed chemotherapy in patients with egfr-mutated non-small cell lung cancer and meningeal metastasis

Conditions: Non-small Cell Lung Cancer Metastatic

Summary: the study conducted to evaluate the efficacy and safety of high-dose furmonertinib (160 mg qd) combined with bevacizumab and pemetrexed intrathecal chemotherapy in nsclc patients with egfr mutations and meningeal metastases.


Eligibility criteria:
inclusion criteria: * histological or cytological localization is nsclc; * confirmed egfr exon 19 deletion mutation(19del) or egfr exon 21l858r mutation (l858r) or egfr exon 20 t790m mutation (t790m)）; * clinical diagnosis of meningeal aggravation: clinical symptoms of intracranial hypertension (headache, dizziness, vomiting, etc.) + imaging confirmation (cerebral mri diagnosis of meningeal aggravation) or cerebrospinal fluid cytology confirmation; * for patients with symptoms who are considered to need temporary brain local. treatment of cough receiving adrenal corticosteroids must be kept stable or reponse for at least 1 week before the first trial of the drug preparation; * newly diagnosed meningeal metastasis, including meningeal metastasis after previous brain surgery and/or local radiotherapy for solid metastatic disease; * patients had not received previous systemic treatment for advanced nsclc or had meningeal metastases after treatment with one third-generation egfr-tki. * obtain informed consent signed by the patient's legal representative; * aged ≥18 years and ≤75 years; * eastern tourism cooperation group (ecog) physical condition evaluation 0-1; * life expectancy ≥12 week; * able to follow the requirements of the study protocol and confirmation procedures, and able to accept cranial wall medications; * contraception. exclusion criteria: * mixed non-small cell and small cell carcinoma, or squamous cell carcinoma as the main pathological type; * known egfr exon 20 c797x mutation (c797x); * history of hypersensitivity reaction to active or inactive excipients of furmonertinib, bevacizumab or pemetrexed or to drugs of similar structure or class to the investigational drug; * brain metastases have previously received whole-brain radiotherapy; * currently participating in an interventional clinical trial, or having received other study drugs or study devices within 4 weeks before the first study drug; * patients who have received solid organ or blood system transplantation; * patients with severe intracranial hypertension symptoms that cannot be relieved by discontinuation of dexamethasone and/or glycol treatment, or patients in intensive care; * ensure control of the patient's symptomatic pericardial, peritoneal, and pleural effusions; * history of cancer in the last five years other malignancies or a history of other malignancies; * recent active digestive events, such as duodenitis, ileitis, intestinal perforation, intestinal catheters, or other conditions that may cause gastrointestinal tract or perforation; or refractory vomiting, chronic gastrointestinal disease, inability to swallow study drugs, or previous colorectal cancer resection that prevents adequate drug absorption; * the patient has a physique that is prone to japanese language learning or has active japanese language learning;central squamous cell carcinoma orpatients at greater risk for hemoptysis; any diamond event ≥ ctcae grade 3, presence of open wounds, injuries or fractures in the 28th century before the first creation; if in the first asthma was accepted 28 days before the organization meeting, the wound treatment should be evaluated by the interval period; * history of arterial thromboembolism within the last 6 months, including vascular cerebral accident, myocardial infarction, transient cerebral contemplation; * history of grade 4 venous thrombosis within the last 6 months, including fire embolism; * the presence of any severe or uncontrolled systemic evidence, including difficult-to-control hypertension (systolic blood pressure ≥150 mmhg and/or diastolic blood pressure ≥100 mmhg), uncontrolled diabetes, etc.; * active infections include, for example, hepatitis b, hepatitis c, and human immunodeficiency virus (hiv) infections (including those requiring intravenous therapy, active hepatitis b infection includes patients with positive hepatitis b surface test based on serological assessment and hepatitis b virus dna \>1000 copies/ml); * previous history of interstitial lung disease, drug-induced interstitial lung disease, pneumonitis requiring steroid therapy, or any evidence of active interstitial lung disease; * the first 28-day inspection of the drug preparation showed lack of adequate bone marrow reserve or organ function（within 2 weeks before blood test,no blood transfusion or blood products, granulocyte colony-stimulating factor or other hematopoietic stimulating factors were used for repair）: * absolute neutrophil count \<1.5 × 109/l; continuous count \<100×109/l; hemoglobin \<90 g/l; * alanine aminotransferase \> 2.5 times upper limit of normal value (upper limit of normal）; aspartate aminotransferase\>2.5 times uln; total bilirubin\>1.5 times uln;or liver transplant patients with ast and/or alt \> 5× uln; * albumin \<30 g/l; * serum creatinine \>1.5 times uln, and creatinine clearance \<50 ml/min（measured or calculated by cockcroft and gault formula); * international normalized ratio (inr) \> 1.5,partially activated zymogen time（aptt\>1.5 times upper limit of normal; * urine protein ≥++, and 24-hour protein \>2.0g; * any of the following bishop criteria: * clinically significant resting electrocardiogram rhythm, respiratory, or morphological abnormalities, such as left bundle branch block, third-degree myocardial insufficiency, and second-degree myocardial insufficiency, within 28 days before the first study drug perfume; * possibility interphase factors that increase the risk of prolonged or arrhythmic events, such as heart failure, congenital long quantum dots syndrome, long quantum dots family history or first-degree relatives 40 sudden death due to coma or known prolonged quantum dots any sudden or difficult to fully compensate low potassium tariffs, low tariff tariffs, and low tariff-to-tariff tariffs during the period; * left ventricular ejection fraction (lvef)left ventricular ejection fraction）\<50%, recent history of myocardial infarction, severe or unstable angina, or coronary artery bypass grafting within the past month or heart failure≥new york heart association (new york heart association (nyha) 2 class; * pregnancy or breastfeeding.

Keywords: egfr mutated meningeal metastasis