Effect of pemetrexed on brain metastases from nonsmall cell lung cancer with wild-type and unknown EGFR status

We aimed to evaluate the effectiveness of pemetrexed-based chemotherapy in wild-type nonsmall-cell lung cancer (NSCLC) patients with brain metastases (BM). Brain metastases are a common cause of mortality in NSCLC patients. For epidermal growth factor receptor (EGFR) wild-type patients, therapeutic options for BM are even limited. Pemetrexed-based therapy is a standard care for patients with EGFR-negative, nonsquamous NSCLC. Besides local therapy, pemetrexed is the preferred chemotherapy for wild-type BM patients, but the efficacy is uncertain. We retrospectively studied 138 NSCLC patients with BM whose EGFR status were unknown or wild-type. All patients received first-line pemetrexed-based chemotherapy from 2010 to 2015. Forty-six of 89 patients with unknown EGFR status were treated with EGFR TKIs after progression. Among the 138 patients, 49 (35.5%) were EGFR wild-type and 89 (64.5%) were unknown EGFR status. The median overall survival (OS), and the median intracranial progression-free survival (iPFS) was 21.0 months, 9.5 months, respectively. Patients who received more than 4 cycles of chemotherapy had significantly longer OS than those who received 3 to 4 cycles (Mantel-Byar X-squared = 6.65, P = .001). In the EGFR wild-type group, the median OS, and the median iPFS was 17.7 months, 7.6 months, respectively. And patients treated with pemetrexed plus platinum tended to have a longer OS than those who were treated with pemetrexed alone (P = .078). In the subgroup with unknown EGFR status, we noted a statistically significant improvement in OS for the patients who received EGFR tyrosine kinase inhibitors (TKIs) after progression of 29 months compared to 20.3 months of the EGFR TKIs naïve arm (P = .027). Pemetrexed shows an ideal effectiveness in EGFR wild-type and unknown status NSCLC patients with BM, and has a favorable control on brain localizations. EGFR wild-type patients can significantly benefit from pemetrexed continuation maintenance.