PMID- 26898607 OWN - NLM STAT- MEDLINE DCOM- 20161104 LR - 20181202 IS - 1872-8332 (Electronic) IS - 0169-5002 (Linking) VI - 93 DP - 2016 Mar TI - A multicenter phase II study of sorafenib in combination with erlotinib in patients with advanced non-small cell lung cancer (KCSG-0806). PG - 1-8 LID - S0169-5002(15)30124-0 [pii] LID - 10.1016/j.lungcan.2015.12.005 [doi] AB - OBJECTIVES: 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). MATERIALS AND 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%). CONCLUSION: 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). CI - Copyright (c) 2015 Elsevier Ireland Ltd. All rights reserved. FAU - Lim, Sun Min AU - Lim SM AD - 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. FAU - Cho, Byoung Chul AU - Cho BC AD - Division of Medical Oncology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, South Korea. FAU - Kim, Sang-We AU - Kim SW AD - Department of Medical Oncology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, South Korea. FAU - Kang, Seok Yun AU - Kang SY AD - Department of Hematology-Oncology, Ajou University School of Medicine, Suwon, South Korea. FAU - Heo, Dae Seog AU - Heo DS AD - Department of Internal Medicine, Seoul National University Hospital, Seoul, South Korea. FAU - Kim, Heung Tae AU - Kim HT AD - National Cancer Center, Goyang-si, South Korea. FAU - Lee, Dae Ho AU - Lee DH AD - Department of Medical Oncology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, South Korea. FAU - Kim, Dong-Wan AU - Kim DW AD - Department of Internal Medicine, Seoul National University Hospital, Seoul, South Korea. FAU - Jung, Minkyu AU - Jung M AD - Division of Medical Oncology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, South Korea. FAU - Choi, Jin-Hyuk AU - Choi JH AD - Department of Hematology-Oncology, Ajou University School of Medicine, Suwon, South Korea. FAU - Shim, Hyo Sup AU - Shim HS AD - Department of Pathology, Yonsei University College of Medicine, Seoul, South Korea. FAU - Choi, Jong Rak AU - Choi JR AD - Department of Laboratory Medicine, Yonsei University, College of Medicine, Seoul, South Korea. FAU - Kim, Joo-Hang AU - Kim JH AD - 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. LA - eng SI - ClinicalTrials.gov/NCT00801385 PT - Clinical Trial, Phase II PT - Journal Article PT - Multicenter Study PT - Research Support, Non-U.S. Gov't DEP - 20151229 PL - Ireland TA - Lung Cancer JT - Lung cancer (Amsterdam, Netherlands) JID - 8800805 RN - 0 (KRAS protein, human) RN - 0 (Phenylurea Compounds) RN - 25X51I8RD4 (Niacinamide) RN - 9ZOQ3TZI87 (Sorafenib) RN - DA87705X9K (Erlotinib Hydrochloride) RN - EC 2.7.10.1 (ErbB Receptors) RN - EC 3.6.5.2 (Proto-Oncogene Proteins p21(ras)) SB - IM MH - Adult MH - Aged MH - Antineoplastic Combined Chemotherapy Protocols/adverse effects/*therapeutic use MH - Carcinoma, Non-Small-Cell Lung/*drug therapy/genetics/mortality/*pathology MH - Disease Progression MH - ErbB Receptors/antagonists & inhibitors/genetics MH - Erlotinib Hydrochloride/administration & dosage MH - Female MH - Humans MH - Lung Neoplasms/*drug therapy/genetics/mortality/*pathology MH - Male MH - Middle Aged MH - Mutation MH - Neoplasm Staging MH - Niacinamide/administration & dosage/analogs & derivatives MH - Phenylurea Compounds/administration & dosage MH - Proto-Oncogene Proteins p21(ras)/genetics MH - Risk Factors MH - Sorafenib MH - Treatment Outcome OTO - NOTNLM OT - Erlotinib OT - Non-small-cell lung cancer OT - Sorafenib EDAT- 2016/02/24 06:00 MHDA- 2016/11/05 06:00 CRDT- 2016/02/23 06:00 PHST- 2015/09/18 00:00 [received] PHST- 2015/12/23 00:00 [revised] PHST- 2015/12/24 00:00 [accepted] PHST- 2016/02/23 06:00 [entrez] PHST- 2016/02/24 06:00 [pubmed] PHST- 2016/11/05 06:00 [medline] AID - S0169-5002(15)30124-0 [pii] AID - 10.1016/j.lungcan.2015.12.005 [doi] PST - ppublish SO - Lung Cancer. 2016 Mar;93:1-8. doi: 10.1016/j.lungcan.2015.12.005. Epub 2015 Dec 29.