title: Efficacy and safety of afatinib in Chinese patients with EGFR-mutated metastatic non-small-cell lung cancer (NSCLC) previously responsive to first-generation tyrosine-kinase inhibitors (TKI) and chemotherapy: comparison with historical cohort using erlotinib.
abstract: BACKGROUND
  Afaitnib has shown anti-tumor activity against metastatic EGFR-mutated NSCLC after prior failure to first generation EGFR-TKI and chemotherapy. We prospectively evaluated the efficacy and safety of afatinib in Chinese patients who previously failed first-generation TKI and chemotherapy under a compassionate use program (CUP) and compared to the erlotinib cohort.
  
  
  METHODS
  Patients who suffered from metastatic EGFR-mutated NSCLC previously responsive to first-generation TKI and chemotherapy received afatinib until progression, loss of clinical benefits or intolerable toxicity. Treatment response, survival and safety were evaluated and compared to the erlotinib cohort.
  
  
  RESULTS
  Twenty-five and 28 patients received afatinib and erlotinib respectively. More patients in the afatinib group had worse performance status (ECOG 2) than the erlotinib group (p = 0.008). After a median follow-up of 12.1 months, afatinib demonstrated comparable objective response rate (ORR) (20.0% vs. 7.1%, p = 0.17) but significantly higher disease control rate (DCR) (68.0% vs. 39.3%, p = 0.04) compared to erlotinib. Median progression-free survival (PFS) (4.1 months [95% CI, 2.7-5.5 months] vs. 3.3 months [95% CI, 2.2-4.3 months], p = 0.97) and overall survival (OS) were not different between the two groups (10.3 months [95% CI, 7.5-13.0 months] vs. 10.8 months [95% CI, 7.4-14.2 months], p = 0.51). Multivariate analyses revealed that age ≤ 70 years and time to progression (TTP) ≥ 18 months for the 1st TKI therapy were prognostic of PFS (p = 0.006 and p = 0.008 respectively). Afatinib caused less rash (60.0% vs. 67.9%, p = 0.04) but more diarrhea (60.0% vs. 10.7%, p = 0.002) compared to erlotinib.
  
  
  CONCLUSIONS
  Afatinib produced encouraging clinical efficacy as 2nd TKI therapy with manageable safety profiles in our Chinese patients after failure to another TKI and systemic chemotherapy. This study was registered at ClinicalTrials.gov (NCT02625168) on 3rd December 2015.
authors.affiliation: Department of Clinical Oncology, Li Ka Shing Faculty of Medicine, Queen Mary Hospital, The University of Hong Kong, 1/F, Professorial Block, 102 Pokfulam Road, Hong Kong, China. vhflee@hku.hk.
authors.forename: Victor H F
authors.initials: VH
authors.lastname: Lee
authors.affiliation: Department of Clinical Oncology, Li Ka Shing Faculty of Medicine, Queen Mary Hospital, The University of Hong Kong, 1/F, Professorial Block, 102 Pokfulam Road, Hong Kong, China. leungkcd@ha.org.hk.
authors.forename: Dennis K C
authors.initials: DK
authors.lastname: Leung
authors.affiliation: Department of Clinical Oncology, Li Ka Shing Faculty of Medicine, Queen Mary Hospital, The University of Hong Kong, 1/F, Professorial Block, 102 Pokfulam Road, Hong Kong, China. ctsz01@ha.org.hk.
authors.forename: Tim-Shing
authors.initials: TS
authors.lastname: Choy
authors.affiliation: Department of Clinical Oncology, Li Ka Shing Faculty of Medicine, Queen Mary Hospital, The University of Hong Kong, 1/F, Professorial Block, 102 Pokfulam Road, Hong Kong, China. lamkaon@hku.hk.
authors.forename: Ka-On
authors.initials: KO
authors.lastname: Lam
authors.affiliation: Department of Clinical Oncology, Li Ka Shing Faculty of Medicine, Queen Mary Hospital, The University of Hong Kong, 1/F, Professorial Block, 102 Pokfulam Road, Hong Kong, China. lammei411@yahoo.com.hk.
authors.forename: Pui-Mei
authors.initials: PM
authors.lastname: Lam
authors.affiliation: Department of Clinical Oncology, Li Ka Shing Faculty of Medicine, Queen Mary Hospital, The University of Hong Kong, 1/F, Professorial Block, 102 Pokfulam Road, Hong Kong, China. leungtw@ha.org.hk.
authors.forename: To-Wai
authors.initials: TW
authors.lastname: Leung
authors.affiliation: Department of Clinical Oncology, Li Ka Shing Faculty of Medicine, Queen Mary Hospital, The University of Hong Kong, 1/F, Professorial Block, 102 Pokfulam Road, Hong Kong, China. dlwkwong@hku.hk.
authors.forename: Dora L W
authors.initials: DL
authors.lastname: Kwong
mesh_terms: D000328:Adult; D000077716:Afatinib; D000368:Aged; D000369:Aged, 80 and over; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality; D015331:Cohort Studies; D066246:ErbB Receptors / Q000235:genetics*; D000069347:Erlotinib Hydrochloride / Q000008:administration & dosage* / Q000009:adverse effects; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009362:Neoplasm Metastasis; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D011799:Quinazolines / Q000008:administration & dosage* / Q000009:adverse effects; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D047428:Protein Kinase Inhibitors; D011799:Quinazolines; D000077716:Afatinib; D000069347:Erlotinib Hydrochloride; C512478:EGFR protein, human; D066246:ErbB Receptors