Phase II Trial of Dose-Dense Pemetrexed, Gemcitabine and Bevacizumab in Patients with Advanced, Non-Small Cell Lung Cancer

• Published in: Clinical lung cancer 2017-05, Vol.18 (3), p.299-302
• Main Authors: Schneider, Bryan J., M.D, Kalemkerian, Gregory P., M.D, Gadgeel, Shirish M., M.D, Valdivieso, Manuel, M.D, Hackstock, Deborah M, Chen, Wei, Ph.D, Heilbrun, Lance K., Ph.D, Ruckdeschel, J.C., M.D, Wozniak, Antoinette J., M.D
• Format: Article
• Language: English
• Subjects: Adenocarcinoma of the lung; Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Bevacizumab - adverse effects; Bevacizumab - therapeutic use; Carcinoma, Non-Small-Cell Lung - drug therapy; Carcinoma, Non-Small-Cell Lung - mortality; Carcinoma, Non-Small-Cell Lung - pathology; Deoxycytidine - adverse effects; Deoxycytidine - analogs & derivatives; Deoxycytidine - therapeutic use; Dose-dense chemotherapy; Drug Dosage Calculations; Fatigue - etiology; Female; Frontline chemotherapy; Hematology, Oncology and Palliative Medicine; Humans; Lung Neoplasms - diet therapy; Lung Neoplasms - mortality; Lung Neoplasms - pathology; Male; Middle Aged; Neoplasm Staging; Neutropenia - etiology; Nonplatinum; Pemetrexed - adverse effects; Pemetrexed - therapeutic use; Pulmonary/Respiratory; Survival Analysis; VEGF inhibition
• ISSN: 1525-7304; 1938-0690
• DOI: 10.1016/j.cllc.2016.11.019

Abstract Introduction Platinum-based chemotherapy is standard for untreated, advanced NSCLC. We investigated the activity and tolerability of the novel combination of dose-dense pemetrexed, gemcitabine and bevacizumab in patients with advanced, NSCLC. Methods This multicenter phase II trial evaluated the safety and efficacy of the combination of pemetrexed (400 mg/m2 ), gemcitabine (1200 mg/m2 ), and bevacizumab (10 mg/kg), given every 14 days in patients with untreated, advanced NSCLC. The primary endpoint was progression-free survival with secondary endpoints of response rate and overall survival. Results Thirty-nine patients were enrolled. Treatment was well tolerated; the most common grade 3-4 toxicities were neutropenia and fatigue. Of the 38 patients evaluable for tumor response, one (3%) had complete response, 15 (39%) had partial response, 12 (31%) had stable disease and 10 (26%) had progressive disease. Median progression-free survival was 6.1 months (95% CI, 4.2 – 7.9) and median overall survival was 18.4 months (95% CI, 13.1 – 29.5). The 1-year overall survival rate was 64% (95% CI, 51 – 81%) and the 2-year overall survival rate was 41% (95% CI, 28 – 60%). Conclusions Treatment with dose-dense pemetrexed, gemcitabine and bevacizumab met the primary endpoint with promising efficacy and a manageable safety profile in patients with untreated advanced NSCLC. This regimen represents a reasonable therapeutic option.