First Line Osimertinib for EGFR Mutation-positive Non-Small Cell Lung Cancer in Real World Chinese Setting

Study Overview
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Brief Summary
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The results of phase III FLAURA study showed a significant PFS benefit for first-line Osimertinib versus standard EGFR-TKIs in patients with EGFR mutation-positive NSCLC, the median PFS was 18.9 months and 10.2 months, respectively. However, only 136 Chinese patients were enrolled in FLAURA study. The objectives of this study are to assess the efficacy and safety of Osimertinib in a real world setting in Chinese patients with locally advanced or metastatic, treatment naïve, epidermal growth factor receptor (EGFR) mutation-positive Non-Small Cell Lung Cancer (NSCLC).

Detailed Description
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Total of  30 study sites are selected for conducting this observational study. Eligible patients will be prospectively and consecutively included. Therefore, the clinical practice in the selected patients group can represent the real-world situation in China, and the patient's medical record will be well documented and archived in those hospitals. All data defined in the protocol will be collected during the study and entered in the Electric Data Capture (EDC), being consistent to the patients' medical records. The most important bias of the study is that patients' characteristics will affect the treatment duration, efficacy and safety, such as, higher proportion of patients with WHO PS 2 3 enroll in the study will result in shorter TTD, poorer effectiveness and higher toxicities than expected. The  30 sites are not randomly selected and potential selection bias exists. To minimize enrolment bias, the patients who are eligible and consent to participate in the current study will be enrolled consecutively as per protocol and without personal preference from investigators. The self-selection bias may exit for the willingness and non-willingness participants. We'll try our best to discuss with the non-willingness participants to make sure the consistency/comparative between the willingness and non-willingness participants. There could be a certain percentage of patients who would lost to follow up, it is unavoidable in clinical study, and is more common in real world study. We can minimize the bias by selecting the hospitals with normative and high-quality clinical practice, trying to collect the reason of lost to follow up and enhancing patient management during the follow up. The above bias is acceptable as this is a real-world study. Only descriptive analysis will be performed for the primary, secondary and exploratory objectives. No statistical comparisons between subgroups will be done.

Official Title
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A Prospective, National, Multi-centric, Non-interventional Study of First Line Osimertinib in Chinese Patients With Locally Advanced/Metastatic，EGFR Mutation-positive NSCLC in Real World Setting

Conditions
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Carcinoma, Non-Small-Cell Lung

Intervention / Treatment
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* Drug: Osimertinib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Ability to provide informed consent, complete all study assessments and have complete medical record; Histologically or cytologically documented locally advanced, metastatic NSCLC, which are not amenable to curative surgery or radiotherapy; With confirmation of the presence of the EGFR mutation. Patients must be treatment- naïve for locally advanced or metastatic NSCLC. Age ≥ 18 years Patients who plan to receive Osimertinib monotherapy as the initial first line treatment based on physician's medical judgement. Exclusion Criteria: Patients who will be or were involved in any other interventional anti-tumour clinical studies for locally advanced/metastatic NSCLC currently or previously Any concomitant condition evaluated by physicians which is not suitable for Osimertinib treatment. Patients who have received the first dose of Osimertinib before the signature of ICF won't be allowed to enroll in.

Ages Eligible for Study
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Minimum Age: 18 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

| Intervention/Treatment |
| --- |
|Drug: Osimertinib|The recommended dose is 80 mg osimertinib once a day until disease progression or unacceptable toxicity according to the prescription information and clinical practice. It can be taken with or without food at the same time each day.|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to discontinuation (TTD) | Time to discontinuation (TTD), is defined as the time from the date of first dose of Osimertinib in this study until the date of Osimertinib discontinuation for any reason including disease progression, treatment toxicity, death or other reason as recorded in CRF. Subjects who are still on treatment at the time of analysis will be censored at the date of last dose received. Lost to follow-up patients will be censored at last documented contact with patient status on treatment. | from the date of first dose of Osimertinib in this study until the date of Osimertinib discontinuation for any reason including disease progression, treatment toxicity, death or other reason as recorded in CRF, assessed up to 36 months. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free survival (PFS) and Progression-free survival rate (PFS rate) | Progression-free survival (PFS), is defined as the time from the date of first dose of Osimertinib in this study until the date of disease progression as recorded in CRF or death (by any cause in the absence of progression) regardless of whether the subject withdraws from therapy or receives another anti-cancer therapy prior to progression, which usually refer to Response Evaluation Criteria In Solid Tumours (RECIST) in clinical practice. Subjects who have not progressed or died at the time of analysis will be censored at the time of the latest date of assessment. If the subject has no evaluable visits after the baseline visit, they will be censored at 0 days unless they die before the planned visit after the baseline visit. Lost to follow-up patients who have not progressed will be censored at last documented contact with patient status non-progression. Progression-free survival rate (PFS rate), is defined as the percentage of patients who do not progress on Osimertinib treatment | from the date of first dose of Osimertinib in this study until the date of disease progression, assessed up to 36 months. | 
| Objective Response Rate (ORR) and Disease Control Rate (DCR) | Objective Response Rate (ORR), is defined as the percentage of patients with complete response or partial response by investigator assessment as recorded in the CRF, which usually refer to Response Evaluation Criteria In Solid Tumours (RECIST) in clinical practice. Disease Control Rate (DCR), is defined as the percentage of patients with non-progression by investigator assessment as recorded in the CRF, which usually refer to Response Evaluation Criteria In Solid Tumours (RECIST) in clinical practice. | from the date of first dose of Osimertinib, assessed up to 6 months. | 
| Overall survival rate (OS rate) | Defined as the proportion of patients who are still alive at a particular time in the study (eg, 1 year or 2 years). The patient should be contacted 1 week after the termination of the corresponding OS analysis data to determine survival status. Lost to follow-up patients who have not progressed will be censored at last documented contact with patient status survival. | from the date of first dose of Osimertinib in this study until the death of patients,assessed up to 48 months. | 
| de novo T790M mutation rate | The mutation rate of de novo T790M test by high sensitive technique (analyzed by Next Generation Sequencing platform). de novo T790M | the baseline and at the time of progression, assessed up to 36 months. | 
| Adverse events/Serious adverse events | Incidence of Adverse Events (AEs): Nature, incidence, severity and seriousness of adverse events, Incidence of Serious Adverse Events (SAEs), which usually be graded by CTCAE v4.03 based on current clinical practice. | from the date of first dose of Osimertinib in this study assessed up to 36 months. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Carcinoma, Non-Small-Cell Lung, Epidermal Growth Factor Receptor mutation, Osimertinib, Real World evidence, non-interventional