Ying Cheng1, Haruyasu Murakami1, Pan-Chyr Yang1, Jianxing He1, Kazuhiko Nakagawa1, Jin Hyoung Kang1, Joo-Hang Kim1, Xin Wang1, Sotaro Enatsu1, Tarun Puri1, Mauro Orlando1, James Chih-Hsin Yang2. 1. Ying Cheng, Jilin Provincial Cancer Hospital, Changchun; Jianxing He, The First Affiliated Hospital of Guangzhou Medical University, Guangdong; Xin Wang, Eli Lilly, Shanghai, China; Haruyasu Murakami, Shizuoka Cancer Center, Shizuoka; Kazuhiko Nakagawa, Kinki University School of Medicine, Osaka; Sotaro Enatsu, Eli Lilly Japan, Kobe, Japan; Pan-Chyr Yang and James Chih-Hsin Yang, National Taiwan University Hospital; James Chih-Hsin Yang, National Taiwan University Cancer Center, Taipei, Taiwan; Jin Hyoung Kang, The Catholic University of Korea, Seoul; Joo-Hang Kim, CHA Bundang Medical Center, CHA University, Gyeonggi-do, Korea; Tarun Puri, Eli Lilly, Gurgaon, Haryana, India; and Mauro Orlando, Eli Lilly Interamérica, Buenos Aires, Argentina. 2. Ying Cheng, Jilin Provincial Cancer Hospital, Changchun; Jianxing He, The First Affiliated Hospital of Guangzhou Medical University, Guangdong; Xin Wang, Eli Lilly, Shanghai, China; Haruyasu Murakami, Shizuoka Cancer Center, Shizuoka; Kazuhiko Nakagawa, Kinki University School of Medicine, Osaka; Sotaro Enatsu, Eli Lilly Japan, Kobe, Japan; Pan-Chyr Yang and James Chih-Hsin Yang, National Taiwan University Hospital; James Chih-Hsin Yang, National Taiwan University Cancer Center, Taipei, Taiwan; Jin Hyoung Kang, The Catholic University of Korea, Seoul; Joo-Hang Kim, CHA Bundang Medical Center, CHA University, Gyeonggi-do, Korea; Tarun Puri, Eli Lilly, Gurgaon, Haryana, India; and Mauro Orlando, Eli Lilly Interamérica, Buenos Aires, Argentina. chihyang@ntu.edu.tw.
Abstract
PURPOSE: To determine whether the addition of pemetrexed to gefitinib (P+G) provides clinical benefit, compared with gefitinib monotherapy, in patients with advanced nonsquamous (NS) non-small-cell lung cancer (NSCLC) and activating epidermal growth factor receptor (EGFR) mutations. PATIENTS AND METHODS: Chemotherapy-naïve for advanced NSCLC patients from China, Japan, Korea, and Taiwan (35 sites) with advanced, EGFR-mutant, NS NSCLC were randomly assigned (2:1; computer-generated, interactive voice response) to open-label pemetrexed (500 mg/m(2) on day 1 of every 21-day cycle) plus gefitinib (250 mg/d [n = 129]) or gefitinib alone (n = 66). The primary end point was progression-free-survival (PFS); secondary end points were time to progressive disease, overall survival, tumor response rates, duration of response, and safety. All end points were assessed in the intent-to-treat and safety population (P+G, n = 126; gefitinib alone, n = 65). RESULTS:PFS was significantly longer with P+G (median, 15.8 months; 95% CI, 12.6 to 18.3 months) than with gefitinib (median, 10.9 months; 95% CI, 9.7 to 13.8 months; adjusted hazard ratio [HR], 0.68; 95% CI, 0.48 to 0.96; one-sided P = .014; two-sided P = .029). Results of EGFR exon 19 deletion and EGFR exon 21 L858R point mutation subgroup analyses were consistent with the intent-to-treat result. P+G, compared with gefitinib alone, resulted in significantly longer time to progressive disease (median, 16.2 v 10.9 months, respectively; HR, 0.66; 95% CI, 0.47 to 0.93) and numerically longer duration of response (median, 15.4 v 11.3 months, respectively; HR, 0.74; 95% CI, 0.50 to 1.08). Tumor response rates did not differ. Overall survival data are immature. Drug-related grade 3 or 4 adverse events were more common with P+G, but toxicities were manageable. CONCLUSION:P+G improved PFS compared with gefitinib alone in East Asian patients with advanced NS NSCLC and activating EGFR mutations. This combination may offer EGFR mutation-positive patients new treatment options and improved clinical outcomes compared with the current standard of care.
RCT Entities:
PURPOSE: To determine whether the addition of pemetrexed to gefitinib (P+G) provides clinical benefit, compared with gefitinib monotherapy, in patients with advanced nonsquamous (NS) non-small-cell lung cancer (NSCLC) and activating epidermal growth factor receptor (EGFR) mutations. PATIENTS AND METHODS: Chemotherapy-naïve for advanced NSCLCpatients from China, Japan, Korea, and Taiwan (35 sites) with advanced, EGFR-mutant, NS NSCLC were randomly assigned (2:1; computer-generated, interactive voice response) to open-label pemetrexed (500 mg/m(2) on day 1 of every 21-day cycle) plus gefitinib (250 mg/d [n = 129]) or gefitinib alone (n = 66). The primary end point was progression-free-survival (PFS); secondary end points were time to progressive disease, overall survival, tumor response rates, duration of response, and safety. All end points were assessed in the intent-to-treat and safety population (P+G, n = 126; gefitinib alone, n = 65). RESULTS: PFS was significantly longer with P+G (median, 15.8 months; 95% CI, 12.6 to 18.3 months) than with gefitinib (median, 10.9 months; 95% CI, 9.7 to 13.8 months; adjusted hazard ratio [HR], 0.68; 95% CI, 0.48 to 0.96; one-sided P = .014; two-sided P = .029). Results of EGFR exon 19 deletion and EGFR exon 21 L858R point mutation subgroup analyses were consistent with the intent-to-treat result. P+G, compared with gefitinib alone, resulted in significantly longer time to progressive disease (median, 16.2 v 10.9 months, respectively; HR, 0.66; 95% CI, 0.47 to 0.93) and numerically longer duration of response (median, 15.4 v 11.3 months, respectively; HR, 0.74; 95% CI, 0.50 to 1.08). Tumor response rates did not differ. Overall survival data are immature. Drug-related grade 3 or 4 adverse events were more common with P+G, but toxicities were manageable. CONCLUSION: P+G improved PFS compared with gefitinib alone in East Asian patients with advanced NS NSCLC and activating EGFR mutations. This combination may offer EGFR mutation-positive patients new treatment options and improved clinical outcomes compared with the current standard of care.
Authors: Kenichi Suda; Paul A Bunn; Christopher J Rivard; Tetsuya Mitsudomi; Fred R Hirsch Journal: J Thorac Oncol Date: 2016-09-15 Impact factor: 15.609