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egfr_non_small_cell_lung_cancer_intracranial_metastases

EGFR Non small cell lung cancer intracranial metastases

Advances in our understanding of genomic alterations in lung cancer have led to the discovery of several driver mutations in non small cell lung cancer 1). The most common are the EGFR activating mutations, which are present in 50% of patients of Asian descent and in 10%–15% of white patients with NSCLC of adenocarcinoma histology 2).

Huang et al., investigated whether tumor mutation status (EGFR, KRAS, ALK, ROS1, BRAF) and treatment history were associated with survival after neurosurgery.

They reviewed the electronic health records of 104 non small cell lung cancer (NSCLC) patients with genomic profiling who underwent neurosurgical resection for symptomatic brain metastases at an academic institution between January 2000 and January 2018.

They used multivariate Cox proportional hazards models to evaluate the association between overall survival (OS) after neurosurgery and clinico-pathological factors including mutation status.

Mean age of patients in this study was 61 (±12) years, and 44% were men. The median OS after neurosurgery was 24 months (95% confidence interval: 18-34). Our multivariate analysis showed that the presence of an EGFR mutation in the tumor was significantly associated with improved OS (hazard ratio [HR] 0.214 p = 0.029), independent of tyrosine kinase inhibitor (TKI) use. Presence of KRAS, ALK, ROS1 and BRAF alterations were not associated with survival (all p > 0.05). Conversely, older age (HR: 1.039; p=0.029), a history of multiple brain irradiation procedures (HR 9.197; p < 0.001) and presence of extracranial metastasis (HR 2.556; p = 0.016) resulted in increased risk of mortality.

Patients requiring surgical resection of an EGFR mutated NSCLC brain metastasis had an associated improved survival compared to patients without this mutation, independent of TKI use. Decreased survival was associated with older age, multiple prior brain radiation therapies and extracranial metastasis 3).


Activating mutations in the epidermal growth factor receptor (EGFR) predict for prolonged progression-free survival in patients with advanced non-small cell lung cancer (NSCLC) treated with EGFR-tyrosine kinase inhibitors (EGFR-TKIs) versus chemotherapy.


A group of patients with non-small cell lung cancer (NSCLC) have tumors that contain an inversion in chromosome 2 that juxtaposes the 5' end of the echinoderm microtubule-associated protein-like 4 (EML4) gene with the 3' end of the anaplastic lymphoma kinase (ALK) gene, resulting in the novel fusion oncogene EML4-ALK


Multi-institutional analysis demonstrated that the use of upfront EGFR-TKI, and deferral of radiotherapy, is associated with inferior OS in patients with EGFR-mutant NSCLC who develop brain metastases. SRS followed by EGFR-TKI resulted in the longest OS and allowed patients to avoid the potential neurocognitive sequelae of WBRT. A prospective, multi-institutional randomized trial of SRS followed by EGFR-TKI versus EGFR-TKI followed by SRS at intracranial progression is urgently needed 4).

References

1)
Zer A, Leighl N. Promising targets and current clinical trials in metastatic non-squamous nsclc. Front Oncol. 2014;4:329. doi: 10.3389/fonc.2014.00329.
2)
Chan BA, Hughes BG. Targeted therapy for non-small cell lung cancer: current standards and the promise of the future. Transl Lung Cancer Res. 2015;4:36–54.
3)
Huang Y, Chow KKH, Aredo JV, Padda SK, Han SS, Kakusa BW, Gephart MH. EGFR mutation status confers survival benefit in non-small cell lung cancer patients undergoing surgical resection of brain metastases: a retrospective cohort study. World Neurosurg. 2019 Jan 30. pii: S1878-8750(19)30210-4. doi: 10.1016/j.wneu.2019.01.112. [Epub ahead of print] PubMed PMID: 30710723.
4)
Magnuson WJ, Lester-Coll NH, Wu AJ, Yang TJ, Lockney NA, Gerber NK, Beal K, Amini A, Patil T, Kavanagh BD, Camidge DR, Braunstein SE, Boreta LC, Balasubramanian SK, Ahluwalia MS, Rana NG, Attia A, Gettinger SN, Contessa JN, Yu JB, Chiang VL. Management of Brain Metastases in Tyrosine Kinase Inhibitor-Naïve Epidermal Growth Factor Receptor-Mutant Non-Small-Cell Lung Cancer: A Retrospective Multi-Institutional Analysis. J Clin Oncol. 2017 Apr 1;35(10):1070-1077. doi: 10.1200/JCO.2016.69.7144. Epub 2017 Jan 23. PubMed PMID: 28113019.
egfr_non_small_cell_lung_cancer_intracranial_metastases.txt · Last modified: 2019/02/03 13:29 by administrador