Impact of epidermal growth factor receptor mutations on intracranial treatment response and survival after brain metastases in lung adenocarcinoma patients

Cao

et al. 2015

Tumor Biol.

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.

Section: Introductionmentioning

confidence: 60%

Section: Discussionmentioning

confidence: 99%

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

Cao

et al. 2015

Tumor Biol.

“…Another study reported an ORR of 58.3% in Chinese adenocarcinoma patients harboring EGFR-activating mutations with asymptomatic BM when treated with erlotinib as second-line therapy (16). EGFR wild-type patients exhibited significantly poorer BM treatment responses and shorter survival after BM diagnosis compared to EGFR-mutant patients (5). The present study demonstrated that the intracranial treatment response was 77.8% (7/9).…”

Section: Discussionsupporting

confidence: 45%

“…Erlotinib was reported to significantly improve the response rate of metastatic brain tumors and survival in lung adenocarcinoma patients with asymptomatic synchronous BM, particularly those with EGFR-activating mutations in exon 19 or 21 (3,4). However, EGFR wild-type patients, compared to mutant patients, exhibited significantly poorer BM treatment responses and a shorter survival after BM diagnosis (5). Pemetrexed is an inhibitor of thymidylate synthase (TS), dihydrofolate reductase and glycinamide ribonucleotide formyltransferase (6).…”

Section: Introductionmentioning

confidence: 99%

Erlotinib with pemetrexed/cisplatin for patients with EGFR wild-type lung adenocarcinoma with brain metastases

Molecular and Clinical Oncology

Yang

et al. 2014

Abstract. Erlotinib and pemetrexed have been approved for the second-line treatment of non-small cell lung cancer. Recent reports indicated that erlotinib and pemetrexed exerted synergistic effects against lung adenocarcinoma. The available treatment options for lung cancer with brain metastases (BM) are currently limited. In the present study, we investigated the efficacy of the combined administration of erlotinib and pemetrexed in 9 patients with epidermal growth factor receptor (EGFR) wild-type lung adenocarcinoma with BM. Pemetrexed (500 mg/m 2 ) and cisplatin (20 mg/m 2 ) were administered on day 1 and days 1-3, respectively. Erlotinib (150 mg) was administered daily on days 4-20. The 9 patients harbored EGFR wild-type mutation in the primary tumor tissues. With regard to the BM, no patients achieved complete remission, 7 patients exhibited a partial response (PR), 1 had stable disease (SD) and 1 had progressive disease (PD). As regards the extracranial tumors, 3 patients exhibited a PR, 2 had SD, 3 had PD and 1 was not applicable. The performance status and the symptoms improved in 3 patients following treatment. The median progression-free survival for intracranial and extracranial disease control was 179 and 146.5 days, respectively. The median overall survival was 197.4 days. Therefore, erlotinib combined with pemetrexed/cisplatin, was found to be effective in the treatment of patients with EGFR wild-type lung adenocarcinoma.

“…Additionally, among the 17 patients with EGFR status, those with the EGFR mutations demonstrated a median OS time of 19.1 months, whereas those with wild-type EGFR mutations had a median OS time of 9.3 months. Similarly, in the retrospective study of Hsiao et al (27), 139 LAC patients, including 89 EGFR mutant and 50 EGFR wild-type patients, were treated with EGFR-TKIs, and around 85% of these patients received radiotherapy. Among the EGFR-mutant patients, those who were treated with WBRT and EGFR-TKIs showed a higher treatment response rate than those who were only treated with EGFR-TKIs.…”

Section: Discussionmentioning

confidence: 96%

Icotinib combined whole brain radiotherapy for patients with brain metastasis from lung adenocarcinoma harboring epidermal growth factor receptor mutation

2016

J. Thorac. Dis.

Background: The brain is a metastatic organ that is most prone to lung adenocarcinoma (LAC). However, the prognosis of patients with brain metastasis remains very poor. In this study, we evaluated the efficacy of icotinib plus whole brain radiation therapy (WBRT) for treating patients with brain metastasis from epidermal growth factor receptor (EGFR)-mutated LAC. Methods: All patients received standard WBRT administered to the whole brain in 30 Gy in 10 daily fractions. Each patient was also instructed to take 125 mg icotinib thrice per day beginning from the first day of the WBRT. After completing the WBRT, maintenance icotinib was administered until the disease progressed or intolerable adverse effects were observed. Cranial progression-free survival (CPFS) and overall survival (OS) times were the primary endpoints. Results: A total of 43 patients were enrolled in this study. Two patients (4.7%) presented a complete response (CR), whereas 20 patients (46.5%) presented a partial response (PR). The median CPFS and OS times were 11.0 and 15.0 months, respectively. The one-year CPFS rate was 40.0% for the patients harboring EGFR exon 19 deletion and 16.7% for the patients with EGFR exon 21 L858R (P=0.027). Conclusions: The concurrent administration of icotinib and WBRT exhibited favorable effects on the patients with brain metastasis. EGFR exon 19 deletion was predictive of a long CPFS following icotinib plus WBRT.