SBRT for Residual Oligometastases of NSCLC After 3rd Generation EGFR-TKIs

Study Overview
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Brief Summary
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This study is an open-label, single-arm phase 2 trial to evaluate the efficacy and safety of stereotactic body radiotherapy (SBRT) for patients with residual oligometastases of NSCLC after 3rd generation EGFR-TKIs.

Official Title
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An Open-label, Single-Arm, Phase 2 Trial of Stereotactic Body Radiotherapy for Patients With Residual Oligometastases of NSCLC After 3rd Generation EGFR-TKIs

Conditions
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NSCLC Stage IV, EGFR T790M

Intervention / Treatment
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* Drug: 3rd generation EGFR-TKI
* Radiation: Consolidative SBRT


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: The patient has a diagnosis of pathologically confirmed NSCLC by tumor biopsy and/or fine-needle aspiration. The patient has a diagnosis of American Joint Committee on Cancer (AJCC) 8th Edition stage IV NSCLC. The patient receives 3rd generation EGFR-TKI in the first line setting or after progression on 1st or 2nd generation EGFR-TKI with either tissue or liquid biopsy-confirmed acquired T790M mutation. The patient is ≥18 years of age and ≤75 years of age at the time of screening. The patient's Karnofsky performance score (KPS) is ≥70 at study entry. The patient has adequate baseline tumor assessment before initiation of 3rd generation EGFR-TKI. The patient has at least one measurable lesion according to Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1. The patient presents with a residual oligometastatic state after 3rd generation EGFR-TKI therapy that would be amenable to consolidative SBRT in the opinion of the investigator. The patient has signed informed consent. Exclusion Criteria: History of another malignancy or concurrent malignancy. Patients with cervical carcinoma in situ or adequately treated basal cell carcinoma who have been disease free for > 5 years are eligible. The patient is pregnant (confirmed by serum b-HCG if applicable) or is breastfeeding. Patients confirmed to be negative for T790M mutation or patients in whom the T790M status is not evaluated after progression on 1st or 2nd generation EGFR-TKI. Patients with uncontrolled epilepsy, mental disorders, drug abuse, or social condition that may affect compliance or ability to sign a written informed consent in the opinion of the investigator. Patients with residual metastatic disease after 3rd generation EGFR-TKI therapy that is deemed not amenable to consolidative SBRT.

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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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 3rd generation EGFR-TKI+ SBRT<br> | Drug: 3rd generation EGFR-TKI<br>* Osimertinib will be administered orally at the dose of 80 mg once daily.<br>* Other names: Osimertinib;Radiation: Consolidative SBRT<br>* Patients who possess oligoresidual disease after 3rd generation EGFR-TKI therapy will be treated with the intent to ablate all residual disease with consolidative SBRT. The choice of dose-fractionation regimen is at the discretion of the treating radiation oncologist. TKI will be continued during and after consolidative SBRT until disease progression or intolerable toxicity.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression Free Survival | PFS was measured from the date of enrollment to the date of disease progression as defined by Response Evaluation Criteria in Solid Tumor (RECIST) Version 1.1 or death due to any cause, whichever occurred first. For patients whose disease did not progress, PFS was evaluated by censoring patients at their most recent imaging. | Two years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Adverse Events | Treatment-related adverse events were assessed and graded according to CTCAE v. 5.0. | Two years | 
| Overall Survival | OS was defined as the time from the date of enrollment until death by any cause. Participants still alive at the time of data analysis were censored at the date of last follow-up. | Two years |