Exon 19 deletion of epidermal growth factor receptor is associated with prolonged survival in brain metastases from non-small-cell lung cancer

Abstract

Brain metastasis (BM) is a poor prognostic factor for non-small-cell lung cancer (NSCLC). Recent studies have shown that oral epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) were effective for BM from NSCLC with EGFR mutation. However, the relationship between EGFR mutations and prognosis of NSCLC BM patients remains to be determined. In this study, we investigated the impact of EGFR mutation status on the survival of BM patients from NSCLC. One hundred six patients with BM from NSCLC were retrospectively reviewed. Thirty-three subjects (24.3 %) were confirmed to have an exon 19 deletion, while another 33 had an exon 21 point mutation (L858R) (24.3 %). Log-rank test and Cox proportional hazards model were used to analyze the impact of variables on survival. The median survival of NSCLC with BM was 8 months. Log-rank test analysis showed that Eastern Cooperative Oncology Group Performance Status (ECOG-PS) at BM (p < 0.0001), control of primary tumor (p = 0.005), pathology (p = 0.01), EGFR mutations (p = 0.045), and 19 exon deletion (p = 0.007) were associated with a longer survival. In a Cox proportional hazards model, EGFR exon 19 deletion (p = 0.034), control of primary tumor (p = 0.024), and ECOG PS at BM (p = 0.006) were found to be independent prognostic factors. Moreover, there were prognostic differences between groups according to Radiation Therapy Oncology Group (RTOG) recursive partitioning analysis (RPA) classification system (p < 0.0001). Exon 19 deletion is an independent prognostic factor in BM from NSCLC. It should be integrated into the prognostic scoring classification system for NSCLC.

EGFR-TKI plus brain radiotherapy versus EGFR-TKI alone in the management of EGFR-mutated NSCLC patients with brain metastases

“…We supposed that may due to clinically more younger patients are tend to receive EGFR-TKIs alone because of the intolerance of potential side-effect of brain RT on the nervous system. Moreover, we found that patients with 19deletion achieved a significant improved OS than patients with 21 L858R after the combination therapy, which was consistence with previous study that 19deletion was a favorable prognosis factor for NSCLC patients with BM (44).…”

“…for the patients with exon 19 deletions, there was no significant difference in PFS between the high and low plasma concentration groups (median survival: 12.0 vs. 17.0 months, P=0.9548), In contrast, the iPFS of 21 L858R mutated patients was significantly different between low and high concentrations of gefitinib (median survival: 8.0 vs. 16.0 months, P<0.05) (41), which indicated that iPFS in patients with exon 21 mutation relied more on concentration than 19deletion patients; and since combined WBRT was associated with elevated CSF concentration of EGFR-TKIs by breaking BBB, both of them seem to partly explain why exon 21 mutation favors combined therapy. Moreover, several previous studies demonstrated that exon 19 and 21 mutations had different response to gefitinib or erlotinib, and patients with exon 19 deletion had longer progression-free survival than those with exon 21 L858R mutation when treated with EGFR-TKIs (42)(43)(44). This may explain the difference of additional value of brain RT as a complement to EGFR-TKIs.…”

EGFR and KRAS Mutations Predict the Incidence and Outcome of Brain Metastases in Non-Small Cell Lung Cancer

“…Other studies found molecular profile to be an independent prognostic factor for patients with NSCLC BM. Li et al noted that EGFR exon 19 deletions were associated with a better prognosis ( p = 0.034) in a population of 106 patients with BM from NSCLC [31]. These results are consistent with ours and suggest that EGFR mutations remain a good prognostic factor even if they are associated with a higher rate of BM relapse after local treatment.…”

The role of EGFR mutation as a prognostic factor in survival after diagnosis of brain metastasis in non-small cell lung cancer: a systematic review and meta-analysis

“…Of the 18 included studies (encompassing a total of 4373 NSCLC patients with brain metastases), 3 had a prospective design [18, 26, 30] and 15 had a retrospective design [14–17, 19–25, 27–29, 31]. Nine included studies were from Asia [14, 15, 17, 18, 20, 24–26, 31], and 9 were from Europe or America [16, 19, 21–23, 27–30].…”