Ying Cheng1, Tony S Mok2, Xiangdong Zhou3, Shun Lu4, Qing Zhou5, Jianying Zhou6, Yingying Du7, Ping Yu8, Xiaoqing Liu9, Chengping Hu10, You Lu11, Yiping Zhang12, Ki Hyeong Lee13, Kazuhiko Nakagawa14, Rolf Linke15, Chew Hooi Wong16, Yiyun Tang17, Fanfan Zhu18, Keith D Wilner19, Yi-Long Wu20. 1. Jilin Provincial Cancer Hospital, Changchun, China. 2. State Key Laboratory of Translational Oncology, Department of Clinical Oncology, Chinese University of Hong Kong, Hong Kong, China. 3. First Affiliated Hospital of Third Military Medical University, Chongqing, China. 4. Shanghai Lung Cancer Center, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China. 5. Guangdong Lung Cancer Institute, Guangdong Provincial People's Hospital and Guangdong Academy of Medical Sciences, Guangzhou, Guangdong, China. 6. First Affiliated Hospital of Zhejiang University, Hangzhou, China. 7. The First Affiliated Hospital of Anhui Medical University, Hefei, China. 8. Sichuan Cancer Hospital, Chengdu, China. 9. Department of Lung Cancer, The Fifth Medical Center of Chinese PLA General Hospital, Beijing, China. 10. Department of Respiratory Medicine, Xiangya Hospital, Central South University, Changsha, China. 11. Department of Thoracic Oncology, Cancer Center, West China Hospital, Sichuan University, Chengdu, China. 12. Department of Medical Oncology, Zhejiang Cancer Hospital, Hangzhou, China. 13. Chungbuk National University Hospital, Chungbuk National University College of Medicine, Cheongju, South Korea. 14. Kindai University Hospital, Osaka, Japan. 15. SFJ Pharmaceuticals Inc., Pleasanton, CA, USA. 16. Pfizer Pte. Ltd., Singapore. 17. Pfizer Oncology, La Jolla, CA, USA. 18. Pfizer Investment Co., Ltd., Shanghai, China. 19. Pfizer Inc., San Diego, CA, USA. 20. Guangdong Lung Cancer Institute, Guangdong Provincial People's Hospital and Guangdong Academy of Medical Sciences, Guangzhou, Guangdong, China. Electronic address: syylwu@live.cn.
Abstract
OBJECTIVES: To compare efficacy and safety of dacomitinib versus gefitinib as first-line therapy for EGFR mutation-positive advanced NSCLC in Asian patients enrolled in the ongoing ARCHER 1050 trial. MATERIALS AND METHODS: In this ongoing, randomized, open-label, phase 3 trial (NCT01774721), eligible patients with newly diagnosed advanced EGFR mutation-positive NSCLC were randomized (1:1) to receive oral dacomitinib 45 mg/day or oral gefitinib 250 mg/day. Randomization, by a central computer system, was stratified by race and EGFR mutation type (exon 19 deletion mutation/exon 21 L858R substitution mutation). The primary endpoint was PFS by blinded independent review. RESULTS: Of 346 Asian patients, 170 were randomized to dacomitinib and 176 to gefitinib. The hazard ratio (HR) for PFS with dacomitinib versus gefitinib was 0.509 (95 % confidence interval [CI]: 0.391-0.662; 1-sided p < 0.0001; median 16.5 months [95 % CI: 12.9-18.4] vs. 9.3 months [95 % CI: 9.2-11.0]). HR for OS with dacomitinib versus gefitinib was 0.759 (95 % CI: 0.578-0.996; median 37.7 months [95 % CI: 30.2-44.7] vs. 29.1 months [95 % CI: 25.6-36.0]). The OS benefit was still maintained in those patients who had a stepwise dose reduction of dacomitinib (to 30 and 15 mg/day). The most common adverse events (AEs) were diarrhea (154 [90.6 %] patients), paronychia (110 [64.7 %]), dermatitis acneiform (96 [56.5 %]), and stomatitis (87 [51.2 %]) with dacomitinib, and diarrhea (100 [56.8 %]), alanine aminotransferase increased (81 [46.0 %]), and aspartate aminotransferase increased (75 [42.6 %]) with gefitinib. Treatment-related serious AEs were reported in 16 (9.4 %) and 8 (4.5 %) patients treated with dacomitinib and gefitinib, respectively. CONCLUSION:First-line dacomitinib was associated with significant prolongation of PFS and improved OS compared with gefitinib in Asian patients with EGFR mutation-positive advanced NSCLC. The AE profiles of dacomitinib and gefitinib in Asian patients were consistent with the overall ARCHER 1050 population.
RCT Entities:
OBJECTIVES: To compare efficacy and safety of dacomitinib versus gefitinib as first-line therapy for EGFR mutation-positive advanced NSCLC in Asian patients enrolled in the ongoing ARCHER 1050 trial. MATERIALS AND METHODS: In this ongoing, randomized, open-label, phase 3 trial (NCT01774721), eligible patients with newly diagnosed advanced EGFR mutation-positive NSCLC were randomized (1:1) to receive oral dacomitinib 45 mg/day or oral gefitinib 250 mg/day. Randomization, by a central computer system, was stratified by race and EGFR mutation type (exon 19 deletion mutation/exon 21 L858R substitution mutation). The primary endpoint was PFS by blinded independent review. RESULTS: Of 346 Asian patients, 170 were randomized to dacomitinib and 176 to gefitinib. The hazard ratio (HR) for PFS with dacomitinib versus gefitinib was 0.509 (95 % confidence interval [CI]: 0.391-0.662; 1-sided p < 0.0001; median 16.5 months [95 % CI: 12.9-18.4] vs. 9.3 months [95 % CI: 9.2-11.0]). HR for OS with dacomitinib versus gefitinib was 0.759 (95 % CI: 0.578-0.996; median 37.7 months [95 % CI: 30.2-44.7] vs. 29.1 months [95 % CI: 25.6-36.0]). The OS benefit was still maintained in those patients who had a stepwise dose reduction of dacomitinib (to 30 and 15 mg/day). The most common adverse events (AEs) were diarrhea (154 [90.6 %] patients), paronychia (110 [64.7 %]), dermatitis acneiform (96 [56.5 %]), and stomatitis (87 [51.2 %]) with dacomitinib, and diarrhea (100 [56.8 %]), alanine aminotransferase increased (81 [46.0 %]), and aspartate aminotransferase increased (75 [42.6 %]) with gefitinib. Treatment-related serious AEs were reported in 16 (9.4 %) and 8 (4.5 %) patients treated with dacomitinib and gefitinib, respectively. CONCLUSION: First-line dacomitinib was associated with significant prolongation of PFS and improved OS compared with gefitinib in Asian patients with EGFR mutation-positive advanced NSCLC. The AE profiles of dacomitinib and gefitinib in Asian patients were consistent with the overall ARCHER 1050 population.