EGFR-mutant Non-small Cell Lung Cancer, NSCLC (Advanced Non-small Cell Lung Cancer), SBRT
Conditions
Keywords
NSCLC, EGFR, TKI, Radiotherapy
Brief 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.
Interventions
DRUGThird-generation EGFR tyrosine kinase inhibitor
administered during induction and maintenance; the specific third-generation EGFR-TKI is not uniformly restricted in the protocol.
DRUGPlatinum plus pemetrexed chemotherapy
cisplatin or carboplatin plus pemetrexed for four 3-week cycles during induction.
DRUGPemetrexed maintenance therapy
administered with the third-generation EGFR-TKI until disease progression or unacceptable toxicity.
RADIATIONConsolidative stereotactic radiotherapy
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.
Sponsors
Fudan University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 |
Outcome results
None listed