Consolidative Stereotactic Radiotherapy for Oligo-Residual Advanced EGFR-Mutant NSCLC After First-Line Third-Generation EGFR-TKI Plus Chemotherapy

NCT07822984 — Phase 2, Not yet recruiting, 374 participants, Fudan University

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Consolidative Stereotactic Radiotherapy for Oligo-Residual Advanced EGFR-Mutant Non-Small Cell Lung Cancer After First-Line Treatment With Third-Generation EGFR Tyrosine Kinase Inhibitor Plus Chemotherapy: A National Multicenter, Randomized Controlled Clinical Trial

Registry	NCT07822984
Status	Not yet recruiting
Phase	Phase 2
Study type	Interventional; randomized, parallel, masking: none, treatment
Enrollment	374 (Estimated)
Sponsor	Fudan University (Other)
Conditions	EGFR-mutant Non-small Cell Lung Cancer, SBRT, NSCLC (Advanced Non-small Cell Lung Cancer)
Interventions	Third-generation EGFR tyrosine kinase inhibitor, Platinum plus pemetrexed chemotherapy, Pemetrexed maintenance therapy, Consolidative stereotactic radiotherapy (Drug, radiation)
Dates	start 2026-10-01 (estimated), primary completion 2030-09-01 (estimated), completion 2030-09-01 (estimated), first posted 2026-09-16, last updated 2026-09-16

-Summary

This national multicenter, randomized controlled clinical trial evaluates the safety and efficacy of consolidative stereotactic radiotherapy in patients with advanced EGFR-mutant non-small cell lung cancer who have oligo-residual disease after four cycles of first-line treatment with third-generation EGFR-TKI plus platinum-based pemetrexed chemotherapy. Eligible participants will be randomized 1:1 to continue third-generation EGFR-TKI plus pemetrexed maintenance therapy alone or to receive stereotactic radiotherapy to all oligo-residual lesions in addition to the same maintenance therapy. The primary endpoint is progression-free survival.

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+Arms and interventions

Arm	Type	Interventions	Description
Radiotherapy plus TKI Group	Experimental	Drug: Third-generation EGFR tyrosine kinase inhibitor; Drug: Platinum plus pemetrexed chemotherapy; Drug: Pemetrexed maintenance therapy; Radiation: Consolidative stereotactic radiotherapy	Consolidative stereotactic radiotherapy plus continued third-generation EGFR-TKI and pemetrexed maintenance therapy.
TKI alone Group	Active comparator	Drug: Third-generation EGFR tyrosine kinase inhibitor; Drug: Platinum plus pemetrexed chemotherapy; Drug: Pemetrexed maintenance therapy	Continued third-generation EGFR-TKI and pemetrexed maintenance therapy alone.

Third-generation EGFR tyrosine kinase inhibitor (Drug): administered during induction and maintenance; the specific third-generation EGFR-TKI is not uniformly restricted in the protocol.
Platinum plus pemetrexed chemotherapy (Drug): cisplatin or carboplatin plus pemetrexed for four 3-week cycles during induction.
Pemetrexed maintenance therapy (Drug): administered with the third-generation EGFR-TKI until disease progression or unacceptable toxicity.
Consolidative stereotactic radiotherapy (Radiation): SRS/SRT/SBRT delivered to all eligible intracranial and/or extracranial oligo-residual lesions, completed as a single course or in staged courses within one month.

+Outcome measures

Primary outcomes

Progression-Free Survival (PFS) [4 years]: The time from randomization to disease progression or death of the patient. Patients who have not yet progressed at the time of analysis will be censored at the date of their last contact.

Secondary outcomes

Overall Survival (OS) [4 years]
Intracranial Progression-Free Survival (iPFS) [4 years]
Health-Related Quality of Life (HRQoL) [4 years]: health-related quality of life assessed using the QLQ-C30 and QLQ-LC13 questionnaires
Incidence of Treatment-Related Toxicities [4 years]: proportion of evaluable participants experiencing treatment-related toxicities, graded according to CTCAE version

Other outcomes

peripheral blood specimens [4 years]: This study requires that peripheral blood specimens be collected as much as possible at the time points specified in the study, and that they be stored and processed in accordance with standard procedures, in order to explore the clinical value of liquid biopsy for oligo-residual disease prediction, early warning of drug resistance, and prognostic assessment.

+Eligibility

Sex: All, ages: 18 Years to 75 Years

Inclusion Criteria:

* Histologically confirmed non-small cell lung cancer.
* Clinical stage IV disease according to the AJCC 9th edition.
* Sensitizing EGFR mutation: EGFR exon 19 deletion or EGFR L858R.
* Age 18-75 years.
* Karnofsky Performance Status score ≥70.
* Complete whole-body imaging assessment before initiation of first-line third-generation EGFR-TKI plus chemotherapy, with at least one evaluable lesion according to RECIST version 1.1.
* No disease progression after completion of four cycles of first-line third-generation EGFR-TKI plus chemotherapy and no unresolved grade ≥3 nonhematologic toxicity.
* Oligo-residual disease after four treatment cycles, with all residual lesions considered suitable for stereotactic radiotherapy by the investigator.
* Written informed consent.

Exclusion Criteria:

* Double primary or multiple primary malignancies, except early skin cancer or cervical carcinoma in situ treated with curative intent and without recurrence or progression for at least five years.
* Pregnancy or breastfeeding, or considered unsuitable by the investigator for PET/CT or brain MRI examination.
* History of uncontrolled epilepsy, central nervous system disease, or psychiatric disorder that, in the investigator's judgment, may interfere with informed consent or participant compliance.
* Residual lesions considered unsuitable for consolidative stereotactic radiotherapy after first-line third-generation EGFR-TKI plus chemotherapy.