P3.16-07 The Impact of Clinical and Molecular Profile of Resected EGFR-Mutant Non-Small Cell Lung Cancer on the Risk of Developing Brain Metastases

Abstract

Brain metastases are common in non-small cell lung cancers (NSCLC) with activating EGFR mutations (EGFRm), occurring in 44%-63% of patients. To date, there are no known clinical or molecular factors to predict the risk of brain metastases in these patients. In this retrospective single-institution study, we identified 106 patients with EGFRm NSCLC who underwent surgery for primary lung tumor. Clinical and demographic data was collected from electronic records. Whole Exome Sequencing (WES) of the primary tumor was performed utilizing the Agilent SureSelect Exome v6+COSMIC baits followed by sequencing on the Illumina HiSeq2500 platform. Development of brain metastases was correlated with clinical/pathologic features, EGFR mutation type, co-mutation of EGFR and other frequently mutated genes; and non-synonymous tumor mutation burden (TMB). Statistical analysis used Fisher exact test for categorical variables, Mann-Whitney test for continuous variables of association with the risk of developing brain metastases, and Gray’s test for the probability of brain metastases over time. Of 106 patients who underwent surgical resection of primary EGFRm NSCLC, WES was successful for 73: 51 (70%) females, 52 (71%) never smokers, 38 (52%) stage I, 14 (19%) stage II and 21 (28%) stage III; 42 (57%) EGFR exon 19 mutation, 30 (41%) exon 21, 1(1%) Exon 20 insertion mutation. Twenty-five patients (34%) developed brain metastases. Patients with brain metastases were younger (median age 61 vs. 65 years, p=0.021), had more advanced stages (p=0.012), with a trend towards higher rates in females (p=0.066). One patient with brain metastases had de-novo EGFR T790M mutation in the primary tumor. No difference was seen regarding smoking history, EGFR mutation type, TP53 co-mutation, and median TMB. The 5-year probability of brain metastases increased with increasing stage (14% stage I; 43% stage II, [HR=3.00], 44% stage III, [HR=3.13], p=0.03), and a trend towards higher probability among females (33% vs. 19%; HR=0.39 for males, p=0.074), and younger patients (37% <65 years vs. 15% >65, HR=0.37 in older patients, p=0.042). There was no difference in probability of brain metastases based on smoking history, ethnicity, EGFR type (33% exon 19 vs. 22% exon 21, p=0.28), TP53 co-mutation (31% vs. 27% without TP53, p=0.59), or TMB (24% TMB≤2.87 vs. 32% TMB>2.87non-synonymous mutations/Mb, p>0.99). While our findings suggest that younger age, advanced stage, and female sex may be associated with the development of BM in EGFRm NSCLC, we could identify no molecular predictor of BM based on EGFR subtype, TP53 co-mutation or TMB.