Sun Min Lim1, Byoung Chul Cho2, Sang-We Kim3, Seok Yun Kang4, Dae Seog Heo5, Heung Tae Kim6, Dae Ho Lee3, Dong-Wan Kim5, Minkyu Jung2, Jin-Hyuk Choi4, Hyo Sup Shim7, Jong Rak Choi8, Joo-Hang Kim9. 1. 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. 2. Division of Medical Oncology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, South Korea. 3. Department of Medical Oncology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, South Korea. 4. Department of Hematology-Oncology, Ajou University School of Medicine, Suwon, South Korea. 5. Department of Internal Medicine, Seoul National University Hospital, Seoul, South Korea. 6. National Cancer Center, Goyang-si, South Korea. 7. Department of Pathology, Yonsei University College of Medicine, Seoul, South Korea. 8. Department of Laboratory Medicine, Yonsei University, College of Medicine, Seoul, South Korea. 9. 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.
Abstract
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).
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 EGFRunknown 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 EGFRWT or EGFRunknown 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).
Authors: Marta Ortega-Muelas; Olga Roche; Diego M Fernández-Aroca; José A Encinar; David Albandea-Rodríguez; Elena Arconada-Luque; Raquel Pascual-Serra; Ismael Muñoz; Isabel Sánchez-Pérez; Borja Belandia; María J Ruiz-Hidalgo; Ricardo Sánchez-Prieto Journal: J Cell Mol Med Date: 2021-10-16 Impact factor: 5.310