TKIs Improve Overall Survival in NSCLC Patients With Leptomeningeal Metastases

Longer overall survival was achieved with TKIs targeting EGFR mutations in non-small cell lung cancer (NSCLC) patients.
Longer overall survival was achieved with TKIs targeting EGFR mutations in non-small cell lung cancer (NSCLC) patients.

Longer overall survival (OS) was achieved with tyrosine kinase inhibitors (TKIs) targeting epidermal growth factor receptor (EGFR) mutations in non-small cell lung cancer (NSCLC) patients with EGFR mutations who had leptomeningeal metastases (LM), a study published the Journal of Thoracic Oncology has shown.1

LM develops when cancer cells metastasize to the membranes that surround the brain (leptomeninges) and the cerebrospinal fluid (CSF). The adverse effect occurs in 10% to 26% of patients with lung cancer and is associated with poor survival.

Treatment strategies include EGFR-TKIs, chemotherapy, whole brain radiotherapy (WBRT), intrathecal chemotherapy, surgery, and ventriculoperitoneal shunt operations; however, treatment is challenging and none of these options are standard. Therefore, researchers from Guangdong Lung Cancer Institute sought to determine the prevalence of EGFR mutations in NSCLC patients with LM and the clinical outcomes of treatments.

Researchers retrospectively examined 5387 patients; 3775 of whom had undergone testing to determine their EGFR gene status. Among those tested, 1258 patients had confirmed EGFR mutations and 2517 had wild-type EGFR (no identified mutations). Of the entire group, 184 (3.4%) had LM; however, incidence of EGFR mutations for patients with LM was significantly higher than for those with wild-type EGFR status (9.4% [118/1258] vs 1.7% [42/2517]).

Overall survival was longer for patients with LM who were treated with TKIs than for patients not treated with TKIs (10 months, 95% CI, 8.9-11.1 vs 3.3 months, 95% CI, 0.5-6.1; P <.001). OS was also longer for patients who were not treated with TKIs prior to LM vs patients who failed initial TKI therapy (12.2 months, 95% CI, 9.7-14.8 vs 9.2 months, 95% CI, 7.8-10.5; P =.016).

OS was not longer for patients who underwent WBRT for LM compared with those who did not undergo WBRT (9.3 months, 95% CI, 8.4-10.3 vs 8.1 months, 95% CI, 4.8-11.4; P =.448). WBRT and TKIs did not result in longer OS compared with TKI therapy alone (9.7 months, 95% CI, 8.7-10.8 vs 10.1 months, 95% CI, 7.1-13.1; P =.778).

Prolonged survival was associated with chemotherapy after LM compared with no chemotherapy (21.0 months, 95% CI, 14.8-27.1 vs 8.7 months, 95% CI, 6.8-10.6; P=0.001).

Overall, these results show that TKIs (P <.001, HR = 0.218, 95% CI, 0.116-0.411) and chemotherapy (P <.001, HR=0.206, 95% CI, 0.092-0.460) significantly influence prolonged survival after LM.

These study findings show that LM is more frequent in NSCLC patients harboring EGFR mutations. Although their study had some limitations, these findings show that EGFR-TKIs are the optimal therapy for LM with EGFR mutations, especially in treatment-naïve patients, the authors noted.


1. Li YS, Jiang BY, Yang JJ, et al. Leptomeningeal metastases in non-small cell lung cancer patients with EGFR mutations. J Thorac Oncol. 2016 Aug 14. doi:10.1016/j.jtho.2016.06.029. [Epub ahead of print]
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