Bevacizumab Plus EGFR-TKIs in Chinese Patients With EGFR-mutant NSCLC: a Real-world Study

Study Overview
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Brief Summary
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This study is a prospective, multicenter, real-world study to investigate the efficacy and safety of bevacizumab plus epidermal growth factor (EGFR) Tyrosine Kinase Inhibitors in Chinese Patients With Stage IIIB/IV EGFR-mutant Non-small Cell Lung Cancer.

Official Title
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Bevacizumab Plus EGFR Tyrosine Kinase Inhibitors in Chinese Patients With Stage IIIB-IV EGFR-mutant Non-small Cell Lung Cancer: a Prospective,Multicenter, Non-interventional,Real-world Study

Conditions
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NSCLC

Intervention / Treatment
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* Drug: Bevacizumab
* Drug: Erlotinib
* Drug: Gefitinib
* Drug: Icotinib
* Drug: Afatinib
* Drug: Dacomitinib
* Drug: Osimertinib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients must meet the following criteria for study entry: Signed Informed Consent Form. Age≥18 years. Histologically or cytologically documented inoperable, locally advanced (Stage IIIB, IIIC), metastatic (Stage IV) or recurrent non-squamous NSCLC. An exon 19 deletion mutation or exon 21 L858R mutation in EGFR has been found clinically, with or without EGFR T790M mutation Eastern Cooperative Oncology Group performance status 0-2 or KPS ≥60 Previous EGFR-TKIs or anti-angiogenic agents or systemic cytotoxic chemotherapy for locally advanced, metastatic or recurrent disease has not been performed. Exclusion Criteria: Patients who meet any of the following criteria will be excluded from study entry: Squamous carcinoma or mixed non-small cell lung cancer with squamous component. Potential hazard for receiving EGFR-TKIs or bevacizumab by clinical evaluations Previous history of receiving EGFR-TKIs or bevacizumab treatment prior to study enrollment Suspected or diagnosed leptomeningeal metastases Chest radiotherapy within 3 months prior to study enrollment Open surgery within 4 weeks prior to study enrollment

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Arm 1:Bevacizumab plus Erlotinib/Gefitinib/Icotinib<br>Patients with EGFR-mutant NSCLC would receive bevacizumab plus first-generation EGFR-TKIs in clinical routine care. Bevacizumab 15 mg/kg or clinical routine dose would be intravenous infusion on day 1 once every 3 weeks. Erlotinib 150 mg tablets once daily or Gefitinib 250mg once daily or Icotinib 125mg three times a day would be administered. | Drug: Bevacizumab<br>* Bevacizumab 15mg/kg or clinical routine dose by intravenous drip infusion on day 1 of a 21-day cycle<br>* Other names: Avastin;Drug: Erlotinib<br>* Erlotinib 150mg, orally once a day<br>* Other names: Tarceva;Drug: Gefitinib<br>* Gefitinib 250mg, orally once a day<br>* Other names: Iressa;Drug: Icotinib<br>* Icotinib 125mg three times a day<br>* Other names: Conmana;|
| Arm 2:Bevacizumab plus Afatinib/Dacomitinib<br>Patients with EGFR-mutant NSCLC would receive bevacizumab plus second-generation EGFR-TKIs in clinical routine care. Bevacizumab 15 mg/kg or clinical routine dose would be intravenous infusion on day 1 once every 3 weeks.Afatinib 40 mg or clinical routine dose once daily or Dacomitinib 45mg or clinical routine dose once daily or clinical routine dose would be administered. | Drug: Bevacizumab<br>* Bevacizumab 15mg/kg or clinical routine dose by intravenous drip infusion on day 1 of a 21-day cycle<br>* Other names: Avastin;Drug: Afatinib<br>* Afatinib 40 mg or clinical routine dose once daily<br>* Other names: Gilotrif;Drug: Dacomitinib<br>* Dacomitinib 45mg or clinical routine dose once daily<br>* Other names: Vizimpro;|
| Arm 3:Bevacizumab plus Osimertinib<br>Patients with EGFR-mutant NSCLC would receive bevacizumab plus third-generation EGFR-TKIs in clinical routine care. Bevacizumab 15 mg/kg or clinical routine dose would be intravenous infusion on day 1 once every 3 weeks. Osimertinib 80 mg tablets once daily would be administered. | Drug: Bevacizumab<br>* Bevacizumab 15mg/kg or clinical routine dose by intravenous drip infusion on day 1 of a 21-day cycle<br>* Other names: Avastin;Drug: Osimertinib<br>* Osimertinib 80 mg once daily<br>* Other names: Tagrisso;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free survival (PFS) for bevacizumab plus first-generation EGFR-TKIs by investigator using RECIST v1.1 | To evaluate the efficacy of bevacizumab combined with first-generation EGFR-TKIs in patients with EGFR-mutant NSCLC as measured by investigators | This is a real-world study. The estimated median PFS for bevacizumab plus first-generation EGFR-TKIs is 18 months according to previous data. | 
| Progression-free survival (PFS) for bevacizumab plus second-generation EGFR-TKIs by investigator using RECIST v1.1 | To evaluate the efficacy of bevacizumab combined with second-generation EGFR-TKIs in patients with EGFR-mutant NSCLC as measured by investigators. | This is a real-world study. The estimated median PFS for bevacizumab plus second-generation EGFR-TKIs is 20 months according to previous data. | 
| Progression-free survival (PFS) for bevacizumab plus third-generation EGFR-TKIs by investigator using RECIST v1.1 | To evaluate the efficacy of bevacizumab combined with third-generation EGFR-TKIs in patients with EGFR-mutant NSCLC as measured by investigators. | This is a real-world study. The estimated median PFS for bevacizumab plus third-generation EGFR-TKIs is 22 months according to previous data. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective response rate (ORR) by investigator using RECIST v1.1 | To evaluate the efficacy of bevacizumab combined with EGFR-TKIs in patients with NSCLC harbouring activating EGFR mutations, with or without EGFR T790M mutation,as measured by investigators assessed objective response rate using RECIST v1.1 | Baseline overall tumor assessment can be performed up to 28 days after the first-dose of treatment. Post-baseline assessment will be performed every six weeks until 1st disease progression, through study completion, an average of 2 years. | 
| Disease control rate (DCR) by investigator using RECIST v1.1 | Disease control rate (DCR) will be analyzed using similar method as objective response rate. | Baseline overall tumor assessment can be performed up to 28 days after the first-dose of treatment. Post-baseline assessment will be performed every six weeks until 1st disease progression, through study completion, an average of 2 years. | 
| Overall survival | To evaluate the efficacy of bevacizumab combined with EGFR-TKIs in patients with NSCLC harbouring activating EGFR mutations,with or without EGFR T790M mutation,as measured by investigators assessed overall survival. | The primary analysis on overall survival is espected to perform on 48 months of follow-up. | 
| Incidence of Treatment-Emergent Adverse Events using CTCAE V5.0 | To evaluate the incidence of Treatment-Emergent Adverse Events of bevacizumab combined with EGFR-TKIs in patients with NSCLC harbouring activating EGFR mutations,with or without EGFR T790M mutation. | This is a real-world study. Safety of the combination treatment is expected to perform until the study completion, an average of 1.5 years,according to CTCAE V5.0. |