title: Different treatment orders achieved similar clinical results: a retrospective study for retreatment of epidermal growth factor receptor tyrosine kinase inhibitors in 120 patients with non-small-cell lung cancer.
abstract: BACKGROUND
  It was reported the retreatment of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) may bring benefit to non-small-cell lung cancer (NSCLC) patients who benefited previously. Nevertheless, the treatment order in most of the prior literature was gefitinib (G) to erlotinib (E), and little was known about whether other treatment order may also bring benefit to the patients.
  
  
  METHODS
  One hundred and twenty NSCLC patients who received EGFR-TKIs treatment twice were enrolled in this study. The safety and effectiveness of the second EGFR-TKIs administration, as well as the influencing factors that contribute to this process, were analyzed retrospectively.
  
  
  RESULTS
  Forty-nine (40.8%) patients were retreated with same kind of EGFR-TKIs: 30 (25%) were G and 19 (15.8%) were E. Seventy-one (59.2%) patients switched to another kind: 55 (45.8%) were G to E and 16 (13.4%) were the reverse. Notably, no differences in clinical benefits were found among the four different treatment orders. For the second administration, the adverse effects of all patients were generally classified as grade I-II and the 1-year survival rate reached 32.5%. The objective response rate, disease control rate, median progression-free survival (PFS), and overall survival was 10.0% (12/120), 52.5% (63/120), 2.3 (95% CI 1.5-3.0) months and 8.0 (95% CI 7.0-8.5) months, respectively. The univariate and multivariate analyses revealed that those patients who benefited from prior EGFR-TKIs were easier to get benefit from the second administration, and the strongest beneficial indicators of the retreatment were PFS of the initial EGFR-TKIs (≥6 months, HR 0.611, 95% CI 0.354-0.901, P = 0.0076) and time interval between the two EGFR-TKIs treatment (≥4 months, HR 0.529, 95% CI 0.328-0.852, P = 0.0088).
  
  
  CONCLUSIONS
  Those patients who benefited from prior EGFR-TKIs were easier to get benefit from the second administration. A time interval of ≥4 months may improve the retreatment, but differences in clinical benefit were not found among different treatment orders. If the retrospective result could be validated further in the future, it would be helpful for rational administration of EGFR-TKIs.
authors.affiliation: Department of Lung Cancer, Affiliated Hospital of Academy of Military Medical Sciences, No. 8 Dongdajie, Beijing, 100071, China.
authors.forename: Chuanhao
authors.initials: C
authors.lastname: Tang
authors.forename: Hongjun
authors.initials: H
authors.lastname: Gao
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Li
authors.forename: Yi
authors.initials: Y
authors.lastname: Liu
authors.forename: Jianjie
authors.initials: J
authors.lastname: Li
authors.forename: Haifeng
authors.initials: H
authors.lastname: Qin
authors.forename: Weixia
authors.initials: W
authors.lastname: Wang
authors.forename: Lili
authors.initials: L
authors.lastname: Qu
authors.forename: Juan
authors.initials: J
authors.lastname: An
authors.forename: Shaoxing
authors.initials: S
authors.lastname: Yang
authors.forename: Xiaoqing
authors.initials: X
authors.lastname: Liu
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000378:metabolism; D018572:Disease-Free Survival; D066246:ErbB Receptors / Q000378:metabolism*; D000069347:Erlotinib Hydrochloride; D005260:Female; D000077156:Gefitinib; D006801:Humans; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D058990:Molecular Targeted Therapy / Q000379:methods*; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D011799:Quinazolines / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D019233:Retreatment; D012189:Retrospective Studies; D012907:Smoking / Q000009:adverse effects / Q000453:epidemiology; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D011799:Quinazolines; D000069347:Erlotinib Hydrochloride; C512478:EGFR protein, human; D066246:ErbB Receptors; D011505:Protein-Tyrosine Kinases; D000077156:Gefitinib