Osimertinib Combined With Intracranial SRT for EGFR-Mutant NSCLC With Symptomatic Brain Metastases

March 24, 2026 updated by: Zhengfei Zhu, Fudan University

Osimertinib With Intracranial Stereotactic Radiotherapy for Newly Diagnosed, Treatment Naive EGFR Mutation Non-Small Cell Lung Cancer With Symptomatic Brain Metastases: A Retrospective, Multicenter, Real-world Study

The goal of this retrospective real-world study is to evaluate the effectiveness and safety of first-line osimertinib combined with early intracranial stereotactic radiotherapy (SRT) in patients with EGFR-mutant non-small cell lung cancer (NSCLC) with symptomatic brain metastases. Eligible patients include adults with stage IV EGFR-mutant NSCLC who received first-line osimertinib monotherapy and early intracranial SRT. Data will be extracted from hospital medical records across multiple centers. The primary endpoint is real-world progression-free survival (rwPFS). Secondary endpoints include overall survival (OS), rwPFS2, time to next treatment or death (TTNT), and time to treatment discontinuation or death (TTD). Exploratory endpoints include CNS progression patterns, CNS progression-free survival (CNS PFS), CNS objective response rate (CNS ORR), and incidence of symptomatic CNS radiation necrosis.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Active, not recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Observational

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
300

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • China
      • Shanghai, China
        • Shanghai Jiao Tong University Affiliated Chest Hospital
    • China
      • Shanghai, China, China, 200032
        • Fudan University Shanghai Cancer Center
    • Hubei
      • Wuhan, Hubei, China
        • Wuhan TongJi Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Sampling Method

Non-Probability Sample

Study Population

The study population will include Stage IV EGFR-mutant NSCLC patients with symptomatic brain metastases who were initially treated with first-line Osimertinib and upfront intracranial SRT during the enrollment period meeting the inclusion and exclusion criteria. First-line therapy must be initated within 6 weeks after initial diagnosis of stage IV EGFRm NSCLC. The patients will be collected across multiple centers in China.

Description

Inclusion Criteria:

  • Age ≥18 years, Male or female
  • Pathologically confirmed Stage IV metastatic non-squamous non-small cell lung cancer (NSCLC) with documented positive EGFR sensitive mutation (EGFR 19del and L858R) and MRI confirmed brain metastases, diagnosed within 6 weeks prior to treatment initiation within baseline period
  • Received first-line osimertinib monotherapy during observation period
  • Upfront brain SRT during observation period
  • Baseline ECOG scored 0-2
  • Symptomatic brain metastases during baseline period*
  • Complete imaging evaluation of systemic lesions (including brain MRI) during baseline period and before osimertinib treatment
  • At least 1 follow-up brain MRI during observation period
  • Baseline BM: ≤10 Brain metastases, largest tumor <10 mL in volume and <3 cm in longest diameter; total cumulative volume ≤15 ml *Symptomatic brain metastases are defined as any neurological symptom in relation to the diagnosed BM, occurred within 30 days after brain metastases diagnosis.

Exclusion Criteria:

  • Leptomeningeal metastases at stage IV NSCLC diagnosis
  • Whole brain radiotherapy treated BM during observation period
  • Patients received other systemic anti-tumor therapy in addition to osimertinib as 1L treatment during observation period
  • Secondary or multiple primary tumors at stage IV NSCLC diagnosis
  • Patients received any adjuvant targeted therapy after previous surgery

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort

Group / Cohort

A group or subgroup of participants in an observational study that is assessed for biomedical or health outcomes.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
First-line osimertinib plus early intracranial SRT
Patients receiving first-line osimertinib combined with early intracranial stereotactic radiotherapy
Drug: Osimertinib
Eligible patients received first-line osimertinib monotherapy for systemic treatment.
Radiation: intracranial stereotactic radiotherapy
Early intracranial stereotactic radiotherapy (SRT) was administered for brain metastases before disease progression on first-line osimertinib. Treatment and follow-up data were collected retrospectively from hospital medical records.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Real-world Progression-Free Survival (rwPFS)
Time Frame: 5 years
The time from index date (i.e. first-line initiation) until documented disease progression or death, whichever occurs first. Any patient not known to have progressed or died at the time of analysis will have rwPFS censored at the date of last assessment showing no progression.
5 years

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Overall Survival (OS)
Time Frame: 5 years
The time from index date until death due to any cause. Any patient not known to have died at the time of analysis will have OS censored at the date they were last known to be alive.
5 years
rwPFS2
Time Frame: 5 years
The time from index date to the earliest of the progression event (following the initial investigator-assessed progression) after first subsequent therapy, or death. Any patient not known to have progressed on first subsequent therapy or died at the time of analysis will have rwPFS2 censored at the date of last assessment showing no progression.
5 years
TTNT (Time to Next Treatment or Death)
Time Frame: 5 years
The time from index date to the start date of the first subsequent treatment or death, whichever occurs first. Any patient not known to have a subsequent treatment or died at the time of analysis will have TTNT cencored at the date of last follow-up without a record of new treatment.
5 years
TTD (Time to Treatment Discontinuation or Death)
Time Frame: 5 years
The time from first-line Osimertinib iniation to discontinuation due to any reason or death, whichever occurs first. Any patient not known to have discontinued first-line Osimertinib or died at the time of analysis will have TTD censored based on the last recorded date on which the patient was known to be on treatment..
5 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Fudan University

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
July 19, 2019

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
March 31, 2025

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
March 31, 2026

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
March 18, 2026

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 18, 2026

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
March 24, 2026

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
March 27, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 24, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
March 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • ESR-24-22678

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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