Yi-Long Wu1, Shun Lu2, Ying Cheng3, Caicun Zhou4, Mengzhao Wang5, Shukui Qin6, You Lu7, Yang Zhang8, Yunzhong Zhu9, Xiangqun Song10, Xin Wang11, Helen Barraclough12, Xiaoqing Zhang13, Haidong Chi13, Mauro Orlando14. 1. Guangdong Lung Cancer Institute, Guangdong General Hospital & Guangdong Academy of Medical Sciences, Guangdong, China. Electronic address: syylwu@live.cn. 2. Lung Cancer Center, Shanghai Chest Hospital, affiliated to Shanghai JiaoTong University, Shanghai, China. 3. Department of Oncology, Cancer Hospital of Jilin Province, Changchun, China. 4. Department of Oncology, Shanghai Pulmonary Hospital, School of Medicine Tongji University Affiliated Cancer Institute, Shanghai, China. 5. Department of Oncology, Peking Union Medical College Hospital, Beijing, China. 6. Department of Oncology, 81st Hospital of the Chinese PLA, Nanjing, China. 7. Department of Oncology, West China School of Medicine, West China Hospital, Sichuan University, Chengdu, China. 8. Department of Oncology, the Second Hospital of Dalian Medical University, Dalian, China. 9. Department of Chest Tumor, Beijing Chest Hospital, affiliated to Capital Medical University, Beijing, China. 10. Cancer Hospital affiliated to Guangxi Medical University, Nanning, China. 11. Asia Pacific Statistical Sciences, Lilly China Drug Development and Medical Affairs Center, Shanghai, China. 12. Asia Pacific Statistical Sciences, Eli Lilly Australia, Sydney, Australia. 13. Oncology, Lilly China Drug Development and Medical Affairs Center, Shanghai, China. 14. Oncology Emerging Markets, Eli Lilly Interamérica Inc., Buenos Aires, Argentina.
Abstract
OBJECTIVES: Retrospective subgroup analysis in JMDB study indicates that the between-arm differences in overall survival (OS) in the East Asian subgroup were consistent with those observed in the entire JMDB study population. This bridging study (JMIL) further evaluated the efficacy and safety of first-line pemetrexed/cisplatin (PC) versus gemcitabine/cisplatin (GC) in Chinese patients with nonsquamous non-small cell lung cancer (NSCLC). The primary endpoint of this local registration trial was designed to compare OS in the combined dataset, consisting of Chinese patients in JMIL and 1252 nonsquamous patients in JMDB. MATERIALS AND METHODS: Chinese patients with stage IIIB/IVnonsquamous NSCLC were randomly assigned (1:1) to 6 cycles maximum (21 days/cycle) of pemetrexed 500mg/m(2)+cisplatin 75mg/m(2) (day 1), or gemcitabine 1250mg/m(2) (days 1 and 8)+cisplatin 75mg/m(2) (day 1). RESULTS: In JMIL, 256 Chinese patients were randomized (PC, n=126; GC, n=130). Patient baseline characteristics were balanced between treatment arms. In the combined dataset, PC was superior to GC in prolonging OS, with adjusted hazard ratio (HR) of 0.87 (95% CI: 0.77-0.98, p=0.023) and median OS of 11.76 versus 10.94 months. In the JMIL-only population, no significant OS difference observed between treatment arms (adjusted HR=1.03 [95% CI: 0.77-1.39, p=0.822]; unadjusted HR=0.996 [95% CI: 0.74-1.33, p=0.980]), nor for other secondary efficacy endpoints. Significantly fewer patients in the PC arm experienced drug-related grade 3/4 toxicities, 54 (43.2%) versus 71 (55.9%) for GC (p=0.045), with significantly lower rates of leukocytopenia, thrombocytopenia, and fatigue. CONCLUSION: This study showed that in the combined population, OS of PC was superior to GC, while in the Chinese-only population, no significant difference was observed; a better safety and risk/benefit profile was found in the PC arm. A PC regimen should be considered as a standard of care in Chinese nonsquamous NSCLC patients in a first-line setting.
RCT Entities:
OBJECTIVES: Retrospective subgroup analysis in JMDB study indicates that the between-arm differences in overall survival (OS) in the East Asian subgroup were consistent with those observed in the entire JMDB study population. This bridging study (JMIL) further evaluated the efficacy and safety of first-line pemetrexed/cisplatin (PC) versus gemcitabine/cisplatin (GC) in Chinese patients with nonsquamous non-small cell lung cancer (NSCLC). The primary endpoint of this local registration trial was designed to compare OS in the combined dataset, consisting of Chinese patients in JMIL and 1252 nonsquamous patients in JMDB. MATERIALS AND METHODS: Chinese patients with stage IIIB/IV nonsquamous NSCLC were randomly assigned (1:1) to 6 cycles maximum (21 days/cycle) of pemetrexed 500mg/m(2)+cisplatin 75mg/m(2) (day 1), or gemcitabine 1250mg/m(2) (days 1 and 8)+cisplatin 75mg/m(2) (day 1). RESULTS: In JMIL, 256 Chinese patients were randomized (PC, n=126; GC, n=130). Patient baseline characteristics were balanced between treatment arms. In the combined dataset, PC was superior to GC in prolonging OS, with adjusted hazard ratio (HR) of 0.87 (95% CI: 0.77-0.98, p=0.023) and median OS of 11.76 versus 10.94 months. In the JMIL-only population, no significant OS difference observed between treatment arms (adjusted HR=1.03 [95% CI: 0.77-1.39, p=0.822]; unadjusted HR=0.996 [95% CI: 0.74-1.33, p=0.980]), nor for other secondary efficacy endpoints. Significantly fewer patients in the PC arm experienced drug-related grade 3/4 toxicities, 54 (43.2%) versus 71 (55.9%) for GC (p=0.045), with significantly lower rates of leukocytopenia, thrombocytopenia, and fatigue. CONCLUSION: This study showed that in the combined population, OS of PC was superior to GC, while in the Chinese-only population, no significant difference was observed; a better safety and risk/benefit profile was found in the PC arm. A PC regimen should be considered as a standard of care in Chinese nonsquamous NSCLCpatients in a first-line setting.
Authors: Ni Jun; Wang Hanping; Si Xiaoyan; Xu Yan; Wang Mengzhao; Zhang Xiaotong; Zhang Li Journal: Thorac Cancer Date: 2020-05-14 Impact factor: 3.500