About 20%–30% of NSCLC patients develop brain metastases. These patients have a poor prognosis, with a median survival of >6 months after whole brain radiotherapy. The EGFR mutation status has prognostic implications in NSCLC patients who develop brain metastasis and EGFR TKIs has demonstrated efficacy in prolonging the survival of these patients.
A retrospective analysis of NSCLC patients with brain metastases who received erlotinib therapy showed a high ORR of 82.4% in those who were EGFR mutation-positive versus no response in unselected patients (P < 0.001). The median time-to-progression (TTP) within the brain for patients harbouring EGFR mutations was 11.7 months (95% CI, 7.9–15.5) compared with 5.8 months (95% CI, 5.2–6.4) for control patients with unknown EGFR mutational status (P = 0.05). OS was 12.9 and 3.1 months, respectively, in the two groups (P = 0.001).
The CTONG0803 (Chinese Thoracic Oncology Group) trial was conducted to examine the efficacy of erlotinib as second-line treatment of patients with confirmed adenocarcinoma or activating EGFR mutation-positive NSCLC who had asymptomatic brain metastases without extracranial progressive disease after 2–6 cycles of first-line platinum-doublet chemotherapy. Patients received erlotinib until intracranial disease progression or development of clinically symptomatic brain metastases. The overall median PFS was 10.1 months (95% CI, 8.97–13.97); median PFS in patients with up to three and more than three brain metastases was 10.2 and 8.3 months, respectively. Median PFS in patients with EGFR wild-type tumours and unknown EGFR mutation status was 8.2 and 15.3 months, respectively; median PFS in patients with EGFR mutations was not reached. Six-month and one-year overall survival (OS) rates were 87% and 74%, respectively. The treatment was well tolerated with no unexpected adverse events or interstitial lung disease-like events. These data suggest that erlotinib monotherapy has promising efficacy for NSCLC patients with asymptomatic brain metastases after first-line systemic chemotherapy. The treatment may also be considered in NSCLC patients with unknown EGFR mutation status.