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Optimal sequence of LT for symptomatic BM in EGFR-mutant NSCLC: a comparative study of first-line EGFR-TKIs
Lishui Niu1, Honghua Wu2, Ruihuan Gao1
1Department of Oncology, Xiangya Hospital, Central South University, 87 Xiangya Road, Kaifu District, Changsha, 410008, Hunan, China.
Background:
The third-generation epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) can penetrate blood-brain barrier and are effective for brain metastases (BMs). There is no consensus on the optimal sequence of local therapy (LT) and EGFR-TKIs for symptomatic BM patients because patients suffering neurological symptoms were not enrolled in most clinical trials.
Methods:
Non-small cell lung cancer (NSCLC) patients with EGFR mutation (EGFRm) and symptomatic BM receiving first-line osimertinib and aumolertinib from two medical centers were collected. All participants were allocated into the third-generation EGFR-TKIs (TKIs) group and the upfront LT (uLT) plus third-generation EGFR-TKIs (TKIs + uLT) group. Demographic data, survival outcomes, treatment failure patterns, and adverse events were evaluated between the two groups. We also conducted subgroup analyses to explore the impact of BM number on survival outcomes.
Results:
86 patients were enrolled, 44 in the TKIs group and 42 in the TKIs + uLT group. There were no significant differences in the short-term response between the groups. TKIs + uLT was associated with significantly longer overall survival (OS) (43 vs. 28 months; hazard ratio [HR], 0.36, 95% confidence interval [CI], 0.17-0.77; p = .011). No differences in progression-free survival (PFS), intracranial PFS (iPFS), failure patterns, or safety were observed. In subgroup analyses of oligo-BM patients, TKIs + uLT could prolong OS (43 vs. 31 months; HR 0.22; 95% CI 0.05-0.92; p = .015).
Conclusions:
EGFRm NSCLC patients with symptomatic BM might benefit from uLT, particularly oligo-BM patients. However, larger prospective cohort studies should be carried out to confirm the responses of the TKIs + uLT scheme.
Insights
Upfront local therapy combined with third-generation EGFR-TKIs may improve overall survival for non-small cell lung cancer patients with symptomatic brain metastases. This combination therapy, particularly for oligo-BM patients, warrants further investigation in larger prospective studies.
Area of Science:
- Oncology
- Neuro-oncology
- Pharmacology
Background:
- Third-generation EGFR-TKIs effectively treat brain metastases (BMs) in EGFR-mutated NSCLC due to blood-brain barrier penetration.
- Optimal sequencing of local therapy (LT) and EGFR-TKIs for symptomatic BMs remains unclear due to limited trial enrollment of neurologically symptomatic patients.
Purpose of the Study:
- To evaluate the efficacy and safety of upfront local therapy (uLT) plus third-generation EGFR-TKIs versus EGFR-TKIs alone in non-small cell lung cancer (NSCLC) patients with symptomatic brain metastases (BMs).
- To explore the impact of BM burden on survival outcomes in this patient population.
Main Methods:
- Retrospective analysis of 86 EGFR-mutated NSCLC patients with symptomatic BMs receiving first-line osimertinib or aumolertinib.
- Patients were divided into two groups: third-generation EGFR-TKIs (TKIs) alone and upfront LT plus third-generation EGFR-TKIs (TKIs + uLT).
- Outcomes assessed included overall survival (OS), progression-free survival (PFS), intracranial PFS (iPFS), treatment failure patterns, and adverse events, with subgroup analyses for BM number.
Main Results:
- No significant difference in short-term response between the TKIs and TKIs + uLT groups.
- The TKIs + uLT group demonstrated significantly longer OS (43 vs. 28 months; HR 0.36) compared to the TKIs group.
- Subgroup analysis revealed prolonged OS in oligo-BM patients receiving TKIs + uLT (43 vs. 31 months; HR 0.22). No differences in PFS, iPFS, failure patterns, or safety were observed.
Conclusions:
- Upfront local therapy in combination with third-generation EGFR-TKIs may benefit EGFR-mutated NSCLC patients with symptomatic BMs, especially those with limited BMs (oligo-BM).
- Larger prospective studies are necessary to confirm the efficacy of the TKIs + uLT treatment strategy.
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