Afatinib has clinical activity in patients with non-small cell lung cancer (NSCLC) who have epidermal growth factor (EGFR) mutations and brain metastases. Both progression-free survival and response were improved compared with chemotherapy, according to data published in the Journal of Thoracic Oncology (doi:10.1016/j.jtho.2015.11.014).1

Brain metastases occur in over 25% of patients with advanced NSCLC, and the rate increases to 44% to 63% for patients with NSCLC tumors driven by EGFR mutations. Brain metastases lead to poor prognoses of typically 1 to 5 months.

Tyrosine kinase inhibitors (TKIs) of EGFR are highly effective for advanced NSCLC driven by EGFR, especially for the common mutations, exon 19 deletions, and L858R point mutations. Though several TKIs are approved for first-line use for EGFR mutated NSCLC, prospective data regarding their use for brain metastases has been scarce.

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This report comes from an international group of investigators who evaluated afatinib versus standard platinum doublet therapy for previously untreated stage IIIB/IV adenocarcinoma patients with confirmed EGFR mutations in two randomized, open-label, phase 3 clinical trials. One of the trials was LUX-Lung 3, which was conducted globally with cisplatin/pemetrexed as the chemotherapy comparator, and other was LUX-Lung 6, which was performed in China, South Korea, and Thailand with cisplatin and gemcitabine. Either study enrolled patients with clinically asymptomatic and controlled brain metastases.

This report analyzed the subgroup of patients with brain metastases at baseline, which included 35 out of 345 (10.1%) randomized patients in LUX-Lung 3 and 46 out of 364 (12.6%) in LUX-Lung 6.

When the results from both trials were pooled together, afatinib, compared to chemotherapy, significantly improved progression-free survival in patients with brain metastases (8.2 vs. 5.4 months; HR, 0.50; P = .0297) and overall response rate was remarkably higher with afatinib (73% vs. 25%). No unexpected safety findings occurred.

“Given the apparent efficacy of afatinib, it is interesting to speculate how TKIs could potentially become incorporated into current standard treatment regimens for patients with brain metastases,” commented the authors. “It is possible, for example, that treatment with a first-line TKI in patients with asymptomatic brain metastases could delay the requirement for whole brain radio therapy, thereby delaying or preventing exposure to the side effects of cranial irradiation.”


1. First-line afatinib versus chemotherapy in patients with non-small cell lung cancer and common epidermal growth factor receptor gene mutations and brain metastases [published online ahead of print January 20, 2016].

J Thorac Oncol. doi: 10.1016/j.jtho.2015.11.014.