Veronika Sarosi1, Gyorgy Losonczy2, Eva Francovszky3, Edina Tolnay4, Szilvia Torok3, Gabriella Galffy2, Balazs Hegedus5, Balazs Dome6, Gyula Ostoros7. 1. Department of Respiratory Medicine, I. Internal Medicine, Medical University, Ifjúság út 13, 7624 Pécs, Hungary. 2. Department of Pulmonology, Semmelweis University, Diósárok utca 1/C, 1125 Budapest, Hungary. 3. National Koranyi Institute of TB and Pulmonology, Pihenő út 1, 1121 Budapest, Hungary. 4. Klinik für Onkologie und Palliativmedizin, Helios-Klinikum-Aue, Gartenstr. 6, 08280 Aue Sachsen, Germany. 5. Division of Thoracic Surgery, Department of Surgery, Medical University of Vienna, Spitalgasse 23, 1090 Vienna, Austria; MTA-SE Tumor Progression Research Group, Hungarian Academy of Sciences, Üllői út 93, 1091 Budapest, Hungary. 6. National Koranyi Institute of TB and Pulmonology, Pihenő út 1, 1121 Budapest, Hungary; Division of Thoracic Surgery, Department of Surgery, Medical University of Vienna, Spitalgasse 23, 1090 Vienna, Austria; Department of Thoracic Surgery, National Institute of Oncology-Semmelweis University, Ráth György u. 7-9, 1122 Budapest, Hungary. Electronic address: balazs.dome@meduniwien.ac.at. 7. Department of Pulmonology, Semmelweis University, Diósárok utca 1/C, 1125 Budapest, Hungary. Electronic address: ostoros@koranyi.hu.
Abstract
OBJECTIVES: Erlotinib is an epidermal growth factor receptor tyrosine-kinase inhibitor (EGFR-TKI), used for the treatment of non-small cell lung cancer. As the clinical significance of KRAS mutational status has not yet been clearly determined in this setting, our aim was to investigate the efficacy of erlotinib in advanced KRAS mutation-negative lung adenocarcinoma patients. MATERIALS AND METHODS: MOTIVATE is an open-label, multicenter, observational trial with Tarceva(®) (erlotinib) monotherapy. Enrolled patients with advanced (stage IIIB/IV) KRAS wild type (WT) lung adenocarcinoma refractory to one or two courses of prior chemotherapy were treated with erlotinib at 150mg/day. The primary endpoint was progression-free survival (PFS). Secondary endpoints were overall survival (OS) and best tumor response rate (RR). RESULTS AND CONCLUSION: In total, 327 patients were included. Median PFS and OS were 3.3 and 14.4 months, respectively. Three patients (1.2%) had complete response, 51 patients (20.2%) had partial response and 123 patients (48.8%) had SD. Significantly longer median PFS and OS were observed in Eastern Oncology Cooperative Group Performance Status (ECOG PS) 0-1 patients, as compared to ECOG PS 2-3 patients. The longest median OS (20.5 months) was found in patients with ECOG PS 0-1 who received erlotinib as a second-line therapy. There was no difference in median OS in cohorts stratified to disease stage and smoking status. Female patients had both longer median PFS and OS. Disease control rate was 70.2%. Our results suggest that erlotinib represents a valid treatment option for patients with KRAS WT lung adenocarcinoma and, moreover, that KRAS mutation analysis could help to identify clinically relevant subgroups of NSCLC patients that may benefit from EGFR-TKI therapy.
OBJECTIVES:Erlotinib is an epidermal growth factor receptor tyrosine-kinase inhibitor (EGFR-TKI), used for the treatment of non-small cell lung cancer. As the clinical significance of KRAS mutational status has not yet been clearly determined in this setting, our aim was to investigate the efficacy of erlotinib in advanced KRAS mutation-negative lung adenocarcinomapatients. MATERIALS AND METHODS: MOTIVATE is an open-label, multicenter, observational trial with Tarceva(®) (erlotinib) monotherapy. Enrolled patients with advanced (stage IIIB/IV) KRAS wild type (WT) lung adenocarcinoma refractory to one or two courses of prior chemotherapy were treated with erlotinib at 150mg/day. The primary endpoint was progression-free survival (PFS). Secondary endpoints were overall survival (OS) and best tumor response rate (RR). RESULTS AND CONCLUSION: In total, 327 patients were included. Median PFS and OS were 3.3 and 14.4 months, respectively. Three patients (1.2%) had complete response, 51 patients (20.2%) had partial response and 123 patients (48.8%) had SD. Significantly longer median PFS and OS were observed in Eastern Oncology Cooperative Group Performance Status (ECOG PS) 0-1 patients, as compared to ECOG PS 2-3 patients. The longest median OS (20.5 months) was found in patients with ECOG PS 0-1 who received erlotinib as a second-line therapy. There was no difference in median OS in cohorts stratified to disease stage and smoking status. Female patients had both longer median PFS and OS. Disease control rate was 70.2%. Our results suggest that erlotinib represents a valid treatment option for patients with KRAS WT lung adenocarcinoma and, moreover, that KRAS mutation analysis could help to identify clinically relevant subgroups of NSCLCpatients that may benefit from EGFR-TKI therapy.
Authors: Robert Fred Henry Walter; Claudia Vollbrecht; Daniel Christoph; Robert Werner; Jan Schmeller; Elena Flom; Georgia Trakada; Aggeliki Rapti; Vasilis Adamidis; Wolfgang Hohenforst-Schmidt; Jens Kollmeier; Thomas Mairinger; Jeremias Wohlschlaeger; Paul Zarogoulidis; Konstantinos Porpodis; Kurt Werner Schmidt; Fabian Dominik Mairinger Journal: J Cancer Date: 2016-10-25 Impact factor: 4.207