Dataset Information

EGFR mutant locally advanced non-small cell lung cancer is at increased risk of brain metastasis.

ABSTRACT:

Background and purpose

Small studies of primarily metastatic non-small cell lung cancer (NSCLC) have suggested an association between EGFR mutation (EGFR+) and likelihood of brain metastasis. However, these studies are confounded by follow-up time bias. We performed a competing risk analysis of brain metastasis in a more uniform locally advanced NSCLC (LA-NSCLC) cohort with known tumor genotype.

Materials and methods

Between 2002 and 2014, 255 patients with LA-NSCLC underwent tumor genotyping for EGFR, ALK and/or KRAS (180 patients had follow-up brain imaging). Cumulative incidence and Fine-Gray regression were performed on clinical variables including genotype and risk of brain metastasis, with death as a competing event.

Results

The proportion of tumors with aberrations in EGFR, ALK and KRAS were 17%, 4% and 28%, respectively. The median follow-up was 68?months. On multivariate analysis, EGFR+ was significantly associated with risk of brain metastasis in the full patient cohort (HR 2.04, 95% CI 1.22-3.39, p?=?0.006) as well as in the subset of patients with brain follow-up imaging (HR 1.91. 95% CI 1.17-3.13, p?=?0.01). This translated to a higher cumulative incidence of brain metastasis in EGFR+ patients at 3 and 5?years (33.3% vs. 23.2 and 43.8% vs. 24.2%, p?=?0.006).

Conclusion

Patients with EGFR+ LA-NSCLC have a significantly higher likelihood of developing brain metastasis after standard combined modality therapy, independent of their longer overall survival. This high-risk genotypic subgroup may benefit from routine surveillance with brain MRI to allow early salvage with targeted systemic- and/or radiation-therapies.

SUBMITTER: Mitra D

PROVIDER: S-EPMC6612652 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

EGFR mutant locally advanced non-small cell lung cancer is at increased risk of brain metastasis.

Mitra Devarati D Chen Yu-Hui YH Li Richard R Hermann Gretchen G Atkins Katelyn K Kozono David D Baldini Elizabeth H EH Aizer Ayal A Chukwueke Ugonma U Mak Raymond H RH

Clinical and translational radiation oncology 20190627

<h4>Background and purpose</h4>Small studies of primarily metastatic non-small cell lung cancer (NSCLC) have suggested an association between EGFR mutation (EGFR+) and likelihood of brain metastasis. However, these studies are confounded by follow-up time bias. We performed a competing risk analysis of brain metastasis in a more uniform locally advanced NSCLC (LA-NSCLC) cohort with known tumor genotype.<h4>Materials and methods</h4>Between 2002 and 2014, 255 patients with LA-NSCLC underwent tumo ...[more]

PMID: 31341973

Similar Datasets

Project description:BackgroundOsimertinib-the third-generation epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI)-has been widely used as a first-line treatment for patients with metastatic EGFR-mutant non-small cell lung cancer (NSCLC). Osimertinib demonstrated central nervous system activity in patients with brain metastasis; however, its efficacy against other distant metastatic organs, including bone and liver, remains unclear. Therefore, we retrospectively analyzed the clinical efficacy of osimertinib in these patients in comparison to other EGFR-TKIs.MethodsClinical data of patients with advanced NSCLC receiving gefitinib/erlotinib (n = 183), afatinib (n = 55), or osimertinib (n = 150) at five medical institutions were retrospectively assessed for progression-free survival (PFS), overall survival (OS), and best overall response rate (ORR).ResultsIn univariate and multivariate analyses, most distant metastases, including the brain and bone, were unrelated to the therapeutic efficacy of osimertinib, although liver metastasis and L858R mutation were independently associated with shorter PFS. PFS and OS in patients with liver metastases were significantly shorter than those in patients without liver metastases (PFS: 7.4 vs. 19.7 months, OS: 12.1 months vs. not reached, respectively). Osimertinib provided significantly longer PFS in patients with brain or bone metastasis and exon 19 deletion than the other EGFR-TKIs. The PFS of patients with liver metastases was not significantly different among the three EGFR-TKI groups. Furthermore, the ORR of osimertinib in patients with liver metastases was significantly attenuated, and the effectiveness was similar to 1st- or 2nd -generation EGFR-TKIs.ConclusionOsimertinib provided better clinical benefits than 1st- and 2nd-generation EGFR-TKIs for patients with EGFR-mutant NSCLC, particularly those with brain or bone metastases and exon 19 deletion; however, its efficacy against liver metastasis was remarkably attenuated. New therapeutic developments for patients with EGFR-mutant NSCLC with liver metastases are needed.

Dataset Information

EGFR mutant locally advanced non-small cell lung cancer is at increased risk of brain metastasis.

Background and purpose

Materials and methods

Results

Conclusion

Publications

EGFR mutant locally advanced non-small cell lung cancer is at increased risk of brain metastasis.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets