Efficacy of epidermal growth factor receptor tyrosine kinase inhibitors for brain metastasis in non-small cell lung cancer patients harboring either exon 19 or 21 mutations.

Abstract

7606 Background: Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR TKI) have not been fully evaluated regarding their efficacy for brain metastasis related to adenocarcinoma of the lung. Methods: This is a prospective study of patients with histologically confirmed adenocarcinoma of the lung, EGFR mutations of either exon 19 or 21, and documented brain metastatic lesions without prior therapy including radiotherapy or radiosurgery or surgical resections. Either erlotinib 150 mg or gefitinib 250 mg was administered every day. EGFR mutations were genotyped by direct sequencing. Results: A total of 23 patients were enrolled. Median age was 57 years (range 37-77). Female accounted for 61% (14/23) and ECOG PS 0-1 74% (17/23). Fourteen patients (61%) had mutations in exon 19 and 9 (39%) exon 21. Synchronous brain metastasis was documented in 15 patients (65%). Seventeen patients used EGFR TKI as second line therapy. Six patients (26%) received erlotinib and 17 gefitinib. Response rate was 70.0%. Median PFS and OS were 6.6 months (95% CI: 0.0-14.7) and 19.8 months (14.1-25.6). Drug modification related to toxicities occurred in 4 patients (17.4%). Patients with exon 19 mutations had longer PFS than those with exon 21 mutations (14.0 months vs 4.6 months; P=0.031); however, no difference in OS was seen (exon 19 15.9 months, exon 21 19.8 months; P=0.498). Patterns of treatment failure included progression of intracranial lesions (42%, 5/12), extracranial lesions (25%, 3/12) and both intra- and extracranial lesions(33%, 4/12). Following progression, 6 patients underwent gamma-knife radiosurgery and 2 patients whole brain radiation. Conclusions: EGFR TKI were effective in NSCLC patients with brain metastasis harboring either exon 19 or 21 mutations. Exon 19 mutations were associated with better disease control when compared to exon 21.