title: A multicenter phase II study of sorafenib in combination with erlotinib in patients with advanced non-small cell lung cancer (KCSG-0806).
abstract: OBJECTIVE
  Sorafenib and erlotinib are potent, orally administered receptor tyrosine kinase inhibitors with antiproliferative and antiangiogenic activities. Given their synergistic activity in combination, we conducted a phase II study to determine the clinical activity of sorafenib in combination with erlotinib in patients with advanced non-small cell lung cancer (NSCLC).
  
  
  METHODS
  Patients with advanced NSCLC who have received one or two prior chemotherapy regimens for metastatic disease, ECOG 0-2, and adequate organ function were eligible. Patients received 400mg twice daily sorafenib and 150 mg daily erlotinib in 28-day cycles. Epidermal growth factor receptor mutation and its downstream pathways were analyzed from available tumor samples. Changes in plasma cytokine and angiogenic factors were correlated with clinical outcomes.
  
  
  RESULTS
  A total of 46 patients were enrolled. Twenty patients (43%) were never smokers and 35 patients (75%) had adenocarcinoma histology. The overall response rate was 30.4%. Response to sorafenib/erlotinib was observed more commonly in patients with EGFR mutation than in those with EGFR wild type (WT) or EGFR unknown tumors (62.5% vs. 6.7% vs. 34.8%; P=0.013). Likewise, DCR was higher among patients with EGFR mutation than in those with EGFR WT or EGFR unknown tumors (87.5% vs. 46.7% vs. 60.9%; P=0.161). The most frequent adverse events (AEs) of all grades were hand-foot skin reaction (67.4%) followed by acneiform rash (58.7%).
  
  
  CONCLUSIONS
  Sorafenib combined with erlotinib is well-tolerated with manageable toxicity and appears to be effective against advanced NSCLC with one or two prior line of systemic treatment (NCT00801385).
authors.affiliation: Division of Medical Oncology, Department of Internal Medicine, CHA University Bundang Medical Center, Seongnam, South Korea; Division of Medical Oncology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, South Korea.
authors.forename: Sun Min
authors.initials: SM
authors.lastname: Lim
authors.affiliation: Division of Medical Oncology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, South Korea.
authors.forename: Byoung Chul
authors.initials: BC
authors.lastname: Cho
authors.affiliation: Department of Medical Oncology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, South Korea.
authors.forename: Sang-We
authors.initials: SW
authors.lastname: Kim
authors.affiliation: Department of Hematology-Oncology, Ajou University School of Medicine, Suwon, South Korea.
authors.forename: Seok Yun
authors.initials: SY
authors.lastname: Kang
authors.affiliation: Department of Internal Medicine, Seoul National University Hospital, Seoul, South Korea.
authors.forename: Dae Seog
authors.initials: DS
authors.lastname: Heo
authors.affiliation: National Cancer Center, Goyang-si, South Korea.
authors.forename: Heung Tae
authors.initials: HT
authors.lastname: Kim
authors.affiliation: Department of Medical Oncology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, South Korea.
authors.forename: Dae Ho
authors.initials: DH
authors.lastname: Lee
authors.affiliation: Department of Internal Medicine, Seoul National University Hospital, Seoul, South Korea.
authors.forename: Dong-Wan
authors.initials: DW
authors.lastname: Kim
authors.affiliation: Division of Medical Oncology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, South Korea.
authors.forename: Minkyu
authors.initials: M
authors.lastname: Jung
authors.affiliation: Department of Hematology-Oncology, Ajou University School of Medicine, Suwon, South Korea.
authors.forename: Jin-Hyuk
authors.initials: JH
authors.lastname: Choi
authors.affiliation: Department of Pathology, Yonsei University College of Medicine, Seoul, South Korea.
authors.forename: Hyo Sup
authors.initials: HS
authors.lastname: Shim
authors.affiliation: Department of Laboratory Medicine, Yonsei University, College of Medicine, Seoul, South Korea.
authors.forename: Jong Rak
authors.initials: JR
authors.lastname: Choi
authors.affiliation: Division of Medical Oncology, Department of Internal Medicine, CHA University Bundang Medical Center, Seongnam, South Korea; Division of Medical Oncology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, South Korea. Electronic address: kim123@cha.ac.kr.
authors.forename: Joo-Hang
authors.initials: JH
authors.lastname: Kim
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality / Q000473:pathology*; D018450:Disease Progression; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000235:genetics; D000069347:Erlotinib Hydrochloride / Q000008:administration & dosage; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009367:Neoplasm Staging; D009536:Niacinamide / Q000008:administration & dosage / Q000031:analogs & derivatives; D010671:Phenylurea Compounds / Q000008:administration & dosage; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics; D012307:Risk Factors; D000077157:Sorafenib; D016896:Treatment Outcome
chemical_list: C117307:KRAS protein, human; D010671:Phenylurea Compounds; D009536:Niacinamide; D000077157:Sorafenib; D000069347:Erlotinib Hydrochloride; D066246:ErbB Receptors; D016283:Proto-Oncogene Proteins p21(ras)
keywords: Erlotinib; Non-small-cell lung cancer; Sorafenib