Lung Cancer Patients With EGFR Mutations Respond Well to TKI Therapy

Researchers from China have discovered a way to offset the brain complications of leptomeningeal metastases (LM) in patients with non-small cell lung cancer (NSCLC). LM are a predictor of poor survival in patients with lung cancer, and found to be more prevalent in patients with NSCLC who carry epidermal growth factor receptor (EGFR) mutations. Patients receiving tyrosine kinase inhibitors (TKIs) targeting EGFR mutations experienced a longer overall survival (OS) than those who did not receive TKIs.

Their findings were first presented, in part, at the 51th Annual Meeting of the American Society of Clinical Oncology, in May 2015, and the 17th Annual Meeting of the Chinese Society for Clinical Oncology, in September 2014, and then recently published in the Journal of Thoracic Oncology.

Of the 5,387 patients examined, 3,775 patients were tested for EGFR gene status. Results showed that of 3,775 patients tested for the EGFR gene status 1,258 patients had confirmed EGRF mutations and 2,517 had wild-type EGFR (no identified mutations). Of the 118 patients harboring EGFR mutations with LM, 109 patients had the most common EGFR mutations, 53 had exon 19 deletions (del 19), and 56 had Leu858Arg mutations (L858R), and as research reveals, will likely experience a worse outcome.

Patients that were given TKIs for treatment of LM had longer OS (by 10 months) than patients who were not prescribed TKIs. Patients who were not prescribed TKIs prior to LM experienced longer OS than those for whom the treatment failed on initial TKIs (12.2 months, 95% CI=9.7-14.8 vs 9.2 months, 95% CI=7.8-10.5, respectively; P = .016). Patients who underwent whole brain radiation therapy (WBRT) for LM did not show longer OS than those without WBRT (9.3 months, 95% CI=8.4-10.3 vs 8.1 months, 95% CI=4.8-11.4; P = .448), and patients treated with both WBRT and TKIs did not have longer OS than those who only received TKIs (9.7 months, 95% CI=8.7-10.8 vs 10.1 months, 95% CI=7.1-13.1; P = .778). Chemotherapy after LM was associated with prolonged survival (by 21 months) when compared with those not receiving this therapy.

“This study had some limitations, however, we showed that OS after LM was longer than that in previous reports, and LM were much more frequent in NSCLC patients harboring EGFR mutations. EGFR-TKIs were the optimal strategy for LM with EGFR mutations, especially TKI treatment-naÏve patients. Nevertheless, active treatment with WBRT, with or without EGFR-TKIs, was not supported by our study,” reported the study authors in an International Association for the Study of Lung Cancer news release.

Lung cancer is the leading cause of cancer deaths worldwide, according to the World Health Organization. In the United States alone, there are projected to be 225,000 new cases diagnosed this year. With further research, this new therapy may help aid treatment decisions for patients with NSCLC.