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

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: Active, not recruiting
• Conditions: Stereotactic Radiation; Osimertinib; Brain Metastases From Non-small Cell Lung Cancer (NSCLC); NSCLC (Advanced Non-small Cell Lung Cancer)
• Intervention / Treatment: Drug: Osimertinib; Radiation: intracranial stereotactic radiotherapy

• Study Type: Observational
• Enrollment (Estimated): 300

Contacts and Locations

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

Eligibility Criteria

• 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

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
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

Outcome Measure	Measure Description	Time Frame
Real-world Progression-Free Survival (rwPFS)	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

Outcome Measure	Measure Description	Time Frame
Overall Survival (OS)	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	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)	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)	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

• Sponsor: Fudan University

Study record dates

Study Major Dates

• Study Start (Actual): July 19, 2019
• Primary Completion (Actual): March 31, 2025
• Study Completion (Estimated): March 31, 2026

Study Registration Dates

• First Submitted: March 18, 2026
• First Submitted That Met QC Criteria: March 18, 2026
• First Posted (Actual): March 24, 2026

Study Record Updates

• Last Update Posted (Actual): March 27, 2026
• Last Update Submitted That Met QC Criteria: March 24, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: NSCLC; Osimertinib; brain metastases; Stereotactic Radiation
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neoplasms by Site; Neoplasms; Respiratory Tract Diseases; Lung Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Neoplasms; Nervous System Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Central Nervous System Neoplasms; Carcinoma, Non-Small-Cell Lung; Brain Neoplasms; osimertinib
• Other Study ID 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