title: Impact of EGFR tyrosine kinase inhibitors versus chemotherapy on the development of leptomeningeal metastasis in never smokers with advanced adenocarcinoma of the lung.
abstract: This study investigated whether epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKI) increase the development of leptomeningeal metastasis (LM) compared with standard chemotherapy in EGFR mutation-enriched non- small cell lung cancer. The incidence of LM was longitudinally assessed in never smokers with advanced adenocarcinoma of the lung enrolled in a phase III randomized controlled study that compared gefitinib with gemcitabine plus cisplatin (GP) as first-line therapy (The First-SIGNAL study). Among 203 patients who were enrolled at the National Cancer Center Hospital (Goyang, Republic of Korea), LM occurred in 32 (15.8 %) with a minimum follow-up time of 55.1 months. The 1-, 2-, and 3-year actuarial incidence rates of LM were 5.3, 10.6, and 24.6 %, respectively. During first-line treatment, LM occurred in 2 patients (2.0 %) treated with gefitinib and in 3 patients (3.2 %) treated with GP. There was no difference in the incidence of LM during first-line treatment between the two groups (P = 0.934). The incidence of LM was significantly increased during second-line EGFR-TKI treatment compared with first-line EGFR-TKI treatment (P = 0.041). During the disease course, the cumulative incidence of LM was not significantly different between the two treatment groups (P = 0.514). The median time to LM was 21.4 and 24.0 months in the gefitinib and GP groups, respectively (P = 0.895). Similar trends were observed in the subset analysis with 23 EGFR-mutant patients. In conclusion, LM predominantly occurred in the late phase of disease in this population. EGFR-TKIs did not affect the incidence or timing of LM development.
authors.affiliation: Center for Lung Cancer, National Cancer Center, Ilsanro 323, Ilsandong-gu, Goyang, Gyeonggi, 410-769, Republic of Korea.
authors.forename: Youngjoo
authors.initials: Y
authors.lastname: Lee
authors.forename: Ji-Youn
authors.initials: JY
authors.lastname: Han
authors.forename: Heung Tae
authors.initials: HT
authors.lastname: Kim
authors.forename: Tak
authors.initials: T
authors.lastname: Yun
authors.forename: Geon Kook
authors.initials: GK
authors.lastname: Lee
authors.forename: Hyae Young
authors.initials: HY
authors.lastname: Kim
authors.forename: Jin Soo
authors.initials: JS
authors.lastname: Lee
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000556:secondary*; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002945:Cisplatin / Q000008:administration & dosage; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D018450:Disease Progression; D066246:ErbB Receptors / Q000037:antagonists & inhibitors*; D005260:Female; D005500:Follow-Up Studies; D000077156:Gefitinib; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000473:pathology*; D008297:Male; D008577:Meningeal Neoplasms / Q000556:secondary*; D009367:Neoplasm Staging; D011379:Prognosis; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D011799:Quinazolines / Q000627:therapeutic use*; D015996:Survival Rate; D000093542:Gemcitabine
chemical_list: D047428:Protein Kinase Inhibitors; D011799:Quinazolines; D003841:Deoxycytidine; C512478:EGFR protein, human; D066246:ErbB Receptors; D002945:Cisplatin; D000077156:Gefitinib; D000093542:Gemcitabine