title: Randomized Phase II Study of Afatinib Plus Simvastatin Versus Afatinib Alone in Previously Treated Patients with Advanced Nonadenocarcinomatous Non-small Cell Lung Cancer.
abstract: OBJECTIVE
  This phase II study examined whether the addition of simvastatin to afatinib provides a clinical benefit compared with afatinib monotherapy in previously treated patients with nonadenocarcinomatous non-small cell lung cancer (NA-NSCLC).
  
  
  METHODS
  Patients with advanced NA-NSCLC who progressed after one or two chemotherapy regimens were randomly assigned to a simvastatin (40 mg/day) plus afatinib (40 mg/day) (AS) arm or to an afatinib (A) arm. The primary endpoint was response rate (RR).
  
  
  RESULTS
  Sixty-eight patients were enrolled (36 in the AS arm and 32 in the A arm). The RR was 5.7% (95% confidence interval [CI], 0.7 to 19.2) for AS and 9.4% (95% CI, 2.0 to 25.0) for A (p=0.440). In arms AS and A, the median progression-free survival (PFS) was 1.0 versus 3.6 months (p=0.240) and the overall survival was 10.0 months versus 7.0 months (p=0.930), respectively. Skin rash, stomatitis, and diarrhea were the most common adverse events in both arms. More grade 3 or 4 diarrhea was observed in arm A (18.8% vs. 5.6% in arm AS). In all patients, the median PFS for treatment including afatinib was not correlated with the status of epidermal growth factor receptor (EGFR) mutation (p=0.122), EGFR fluorescence in situ hybridization (p=0.944), or EGFR immunohistochemistry (p=0.976). However, skin rash severity was significantly related to the risk of progression for afatinib (hazard ratio for skin rash grade ≥ 2 vs. grade < 2, 0.44; 95% CI, 0.25 to 0.78; p=0.005).
  
  
  CONCLUSIONS
  There were no significant differences in the efficacy between AS and A arms in patients with NA-NSCLC.
authors.affiliation: Center for Lung Cancer, Research Institute and Hospital, National Cancer Center, Goyang, Korea.
authors.forename: Youngjoo
authors.initials: Y
authors.lastname: Lee
authors.affiliation: Department of Hematology-Oncology, Chungbuk National University Hospital, Cheongju, Korea.
authors.forename: Ki Hyeong
authors.initials: KH
authors.lastname: Lee
authors.affiliation: Center for Lung Cancer, Research Institute and Hospital, National Cancer Center, Goyang, Korea.
authors.forename: Geon Kook
authors.initials: GK
authors.lastname: Lee
authors.affiliation: Center for Lung Cancer, Research Institute and Hospital, National Cancer Center, Goyang, Korea.
authors.forename: Soo-Hyun
authors.initials: SH
authors.lastname: Lee
authors.affiliation: Center for Lung Cancer, Research Institute and Hospital, National Cancer Center, Goyang, Korea.
authors.forename: Kun Young
authors.initials: KY
authors.lastname: Lim
authors.affiliation: Biometric Research Branch, Research Institute and Hospital, National Cancer Center, Goyang, Korea.
authors.forename: Jungnam
authors.initials: J
authors.lastname: Joo
authors.affiliation: Center for Lung Cancer, Research Institute and Hospital, National Cancer Center, Goyang, Korea.
authors.forename: Yun Jung
authors.initials: YJ
authors.lastname: Go
authors.affiliation: Center for Lung Cancer, Research Institute and Hospital, National Cancer Center, Goyang, Korea.
authors.forename: Jin Soo
authors.initials: JS
authors.lastname: Lee
authors.affiliation: Center for Lung Cancer, Research Institute and Hospital, National Cancer Center, Goyang, Korea.
authors.forename: Ji-Youn
authors.initials: JY
authors.lastname: Han
mesh_terms: D000328:Adult; D000077716:Afatinib; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D014408:Biomarkers, Tumor; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology*; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D011799:Quinazolines / Q000008:administration & dosage / Q000627:therapeutic use*; D019233:Retreatment; D019821:Simvastatin / Q000008:administration & dosage; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D014408:Biomarkers, Tumor; D011799:Quinazolines; D000077716:Afatinib; D019821:Simvastatin
keywords: EGFR mutation; EGFR tyrosine kinase inhibitor; Non-small-cell lung carcinoma; Squamous cell carcinoma; Statin