EGFR Inhibitor Improves Survival in Lung Cancer Patients with Brain Metastases

Afatinib showed significant improvement in progression-free survival and objective response rate in non-small cell lung cancer patients.

An epidermal growth factor (EGFR) inhibitor was found to improve survival rates for lung cancer patients with brain metastases compared with standard platinum doublet chemotherapy in a recent study.

For patients who have been diagnosed with non-small cell lung cancer (NSCLC), more than 25% have the cancer spread from their lungs to their brains. For those with an EGFR mutation, the number of patients increases by 44% to 63%. Unfortunately, the survival rate for these patients tends to range from 1 to 5 months.

Although EGFR tyrosine kinase inhibitors (TKI) have efficacy for NSCLC driven by EGFR mutations — especially exon 19 deletions and L858R point mutations – there hasn’t been much data gathered for EGFR TKI patients with brain metastases.

During a pair of phase 3 clinical trials published in the Journal of Thoracic Oncology, researchers studied how the TKI afatinib compares with standard platinum doublet therapy for previously untreated patients with stage 3b/4 adenocarcinoma with EGFR mutations.

The LUX-Lung 3 study was performed globally using cisplatin/pemetrexed chemotherapy treatment. The LUX-Lung 6 study was conducted in China, South Korea, and Thailand using cisplatin and gemcitabine chemotherapy.

The researchers found that when compared with platinum-based chemotherapy, afatinib showed significant improvement in progression-free survival (PFS), objective response rate (ORR), and patient-reported outcomes.

The study also showed that afatinib combined with an EGFR TKI improved overall survival (OS) in patients with an EGFR Del19 mutation, the mFprost common EGFR aberration in patients with NSCLC.

The LUX-Lung 3 clinical trial randomized 345 patients, of which a total of 35 (10.1%) had brain metastases present at baseline with the Del19 and L858R EGFR mutations. In the LUX-Lung 6 trial, 46 out of 364 patients (12.6%) had brain metastases with the Del19 and L858R EGFR mutations.

Combined data from both trials showed afatinib significantly improved PFS in brain metastases patients (8.2 vs. 5.4 months; HR, 0.50; p=0.0297) compared with chemotherapy. ORR was also higher with afatinib (73% vs. 25%).

For patients with brain metastases administered afatinib, adverse events were found to be similar to patients without brain metastases and there were no unexpected safety findings.

"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,” the study authors wrote. “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."