EGFR-Mutant Non-Small-Cell Lung Cancer Intracranial Metastases [Neurosurgery Wiki]

This page is read only. You can view the source, but not change it. Ask your administrator if you think this is wrong.
====== EGFR-Mutant Non-Small-Cell Lung Cancer Intracranial Metastases ======

{{rss>https://pubmed.ncbi.nlm.nih.gov/rss/search/1N9mJ43b_PBVOlS0xE1Dj2yFoIVE4UnZvh_hyxt-7dDrzV2MXt/?limit=15&utm_campaign=pubmed-2&fc=20250402160211}}
----

----
In recent years, accompanied by dramatic improvements in systemic disease control and advancements in brain imaging, the incidence of [[non-small cell lung cancer]] [[brain metastases]] (BMs) has increased. Patients with mutated EGFR have a much higher possibility of BMs than those with wild-type EGFR. Previous studies have reported that the 3-year cumulative rate of BMs ranges from 29.4% to 60.3% in patients with mutated EGFR and from 22% to 28.2% in patients with wild-type EGFR
((Heon S, Yeap BY, Britt GJ, Costa DB, Rabin MS, Jackman DM, et al. Development of central nervous system metastases in patients with advanced non-small cell lung cancer and somatic egfr mutations treated with gefitinib or erlotinib. Clin Cancer rese: an Off J Am Assoc Cancer Res (2010) 16(23):5873–82. doi: 10.1158/1078-0432.CCR-10-1588))
((Han G, Bi J, Tan W, Wei X, Wang X, Ying X, et al. A retrospective analysis in patients with egfr-mutant lung adenocarcinoma: Is egfr mutation associated with a higher incidence of brain metastasis? Oncotarget (2016) 7(35):56998–7010. doi: 10.18632/oncotarget.10933))
((Hsu F, De Caluwe A, Anderson D, Nichol A, Toriumi T, Ho C. Egfr mutation status on brain metastases from non-small cell lung cancer. Lung Cancer (2016) 96:101–7. doi: 10.1016/j.lungcan.2016.04.004))
((Su PL, Wu YL, Chang WY, Ho CL, Tseng YL, Lai WW, et al. Preventing and treating brain metastases with three first-line egfr-tyrosine kinase inhibitors in patients with egfr mutation-positive advanced non-small cell lung cancer. Ther Adv Med Oncol (2018) 10:1758835918797589. doi: 10.1177/1758835918797589))
((Rangachari D, Yamaguchi N, VanderLaan PA, Folch E, Mahadevan A, Floyd SR, et al. Brain metastases in patients with egfr-mutated or alk-rearranged non-Small-Cell lung cancers. Lung Cancer (2015) 88(1):108–11. doi: 10.1016/j.lungcan.2015.01.020))
((Mitra D, Chen YH, Li R, Hermann G, Atkins K, Kozono D, et al. Egfr mutant locally advanced non-small cell lung cancer is at increased risk of brain metastasis. Clin Transl Radiat Oncol (2019) 18:32–8. doi: 10.1016/j.ctro.2019.06.008))
((Ouyang W, Yu J, Zhou Y, Hu J, Huang Z, Zhang J, et al. Risk factors of metachronous brain metastasis in patients with egfr-mutated advanced non-small cell lung cancer. BMC Cancer (2020) 20(1):699. doi: 10.1186/s12885-020-07202-8)).
----
The third-generation [[epidermal growth factor receptor tyrosine kinase inhibitor]]s (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.

[[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.

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
((Niu L, Wu H, Gao R, Chen L, Wang J, Duan H, Long Y, Xie Y, Zhou Q, Zhou R. Optimal sequence of LT for symptomatic BM in EGFR-mutant NSCLC: a comparative study of first-line EGFR-TKIs with/without upfront LT. J Cancer Res Clin Oncol. 2024 Feb 19;150(2):94. doi: 10.1007/s00432-023-05538-9. PMID: 38369644; PMCID: PMC10874906.))

===== Treatment =====

[[EGFR-Mutant Non-Small-Cell Lung Cancer Intracranial Metastases Treatment]]

===== Outcome =====

see [[Brain metastases outcome]].
----


A retrospective study involving 72 advanced EGFR-mutant NSCLC patients with brain metastases at the Vietnam National Cancer Hospital were conducted. Patients were divided into 2 groups: EGFR-TKI (erlotinib) monotherapy and EGFR-TKI combined with locoregional therapy (γ knife surgery - GKS or whole-brain radiation therapy). Evaluation criteria included clinical and laboratory characteristics, central nervous system (CNS) progression time, progression-free survival (PFS), overall survival (OS), T790M mutation rate, and adverse events.

Epidermal growth factor receptor tyrosine kinase inhibitor monotherapy patients had better performance status (PS), fewer CNS symptoms, and significantly fewer brain metastases (p < 0.05). Median PFS and OS were 11 and 25 months, respectively, in both groups. Patients with PS 0-1 had longer median PFS (15 months) than those with PS 2 (7 months) (p = 0.039). Exon 19 deletion patients in both groups had longer median OS (26 months) than those with L858R exon 21 (15 months) (p = 0.023). Patients with T790M mutation who received osimertinib after progression had longer median OS (41 months vs. 23 months, p = 0.0001). Median time to CNS progression was 13.9 months (48 patients). Longer time to CNS progression correlated with longer OS (R2 = 0.89).

Epidermal growth factor receptor tyrosine kinase inhibitor therapy, with or without locoregional therapy, is effective for advanced EGFR-mutant NSCLC patients with brain metastases. Exon 19 deletion patients had better prognosis
((Linh DM, Thinh TH, Hieu NV, Duc NM. Treatment outcomes of EGFR-TKI with or without locoregional brain therapy in advanced EGFR-mutant non-small cell lung cancer patients with brain metastases. Contemp Oncol (Pozn). 2023;27(2):71-79. doi: 10.5114/wo.2023.129366. Epub 2023 Jul 11. PMID: 37794989; PMCID: PMC10546967.))