Affiliation:
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...
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/m2 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.
Publisher
American Society of Clinical Oncology (ASCO)
Cited by
152 articles.
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