Prognostic analysis of patients with non-small cell lung cancer harboring exon 19 or 21 mutation in the epidermal growth factor gene and brain metastases

Abstract

Background: In 1997, the Radiation Therapy Oncology Group (RTOG) put forward the recursive partitioning analysis classification for the prognosis of brain metastases (BMs), but this system does not take into account the epidermal growth factor receptor (EGFR) mutations. The aim of the study is to assess the prognosis of patients with EGFR-mutated non-small cell lung cancer (NSCLC) and BMs in the era of tyrosine kinase inhibitor (TKI) availability.

Methods: This was a retrospective study of consecutive patients with EGFR-mutated (exon 19 or 21) NSCLC diagnosed between 01/2011 and 12/2014 at the Tianjin Medical University Cancer Institute & Hospital and who were ultimately diagnosed with BMs. The patients were stage I-III at initial presentation and developed BMs as the first progression. Overall survival (OS), OS after BM diagnosis (mOS), intracranial progression-free survival (iPFS), response to treatment, and adverse reactions were analyzed.

Results: Median survival was 35 months, and the 1- and 2- year survival rates were 95.6% (108/113) and 74.3% (84/113). The 3-month CR + PR rates of radiotherapy(R), chemotherapy(C), targeted treatment(T), and targeted treatment + radiotherapy(T+R) after BMs were 63.0% (17/27), 26.7% (4/15), 50.0% (7/14), and 89.7% (35/39), respectively. The median survival of the four treatments was 20, 9, 12, and 25 months after BMs, respectively (P = 0.001). Multivariable analysis showed that < 3 BMs (odds ratio (OR) = 3.34, 95% confidence interval (CI): 1.89-5.91, P < 0.001) and treatment after BMs (OR = 0.68, 95%CI: 0.54-0.85, P = 0.001) were independently associated with better prognosis.

Conclusions: The prognosis of patients with NSCLC and EGFR mutation in exon 19 or 21 after BM is associated with the number of brain metastasis and the treatment method. Targeted treatment combined with radiotherapy may have some advantages over other treatments, but further study is warranted to validate the results.

Keywords: Brain metastasis; Non-small cell lung cancer; Prognosis; Treatment; epidermal growth factor receptor mutation.

Fig. 1

Survival analysis of patients with non-small cell lung cancer (NSCLC) and brain metastases (BMs). a Overall survival (OS). b Overall survival after BM diagnosis (mOS). c intracranial progression-free survival (iPFS)

Fig. 2

Survival of patients according to clinical characteristics. a Patients with < 3 brain metastases (BMs) showed survival advantage compared with those with > 3 BMs (25 (193.4–30.6) vs. 9 (6.9–11.1) months, P < 0.001). b Patients with ECOG score ≤ 2 showed a survival advantage compared with those with ECOG > 2 (21 (14.8–27.2) vs. 7 (3.8–10.2), P < 0.001). c After BMs, the median survival of the four groups of treatment was 20 (range, 6.0–34.0) months for radiotherapy, 9 (range, 7.0–11.1) months for chemotherapy, 12 (range, 5.7–18.3) months for targeted therapy, and 25 (range, 16.7–33.3) months for targeted therapy combined with radiotherapy (P < 0.05). d The median intracranial progression-free survival (iPFS) among the four treatments was 12 (range, 0–24.6) months for radiotherapy, 7 (range, 2.5–11.5) months for chemotherapy, 10 (range, 5.3–14.7) months for targeted therapy, and 21 (range, 14.0–28.0) months for targeted therapy combined with radiotherapy (P < 0.05)