Song-Tao Xu1, Jun-Jie Xi1, Wen-Zhao Zhong2, Wei-Min Mao3, Lin Wu4, Yi Shen5, Yong-Yu Liu6, Chun Chen7, Ying Cheng8, Lin Xu9, Jun Wang10, Ke Fei11, Xiao-Fei Li12, Jian Li13, Cheng Huang14, Zhi-Dong Liu15, Shun Xu16, Ke-Neng Chen17, Shi-Dong Xu18, Lun-Xu Liu19, Ping Yu20, Bu-Hai Wang21, Hai-Tao Ma22, Hong-Hong Yan2, Xue-Ning Yang2, Yong-Xing Zhang1, Jia-Cheng Yin1, Qun Wang1, Yi-Long Wu23. 1. Zhongshan Hospital, Fudan University, Shanghai, China. 2. Guangdong Lung Cancer Institute, Guangdong General Hospital & Guangdong Academy of Medical Sciences, Guangzhou, China. 3. Zhejiang Cancer Hospital, Hangzhou, China. 4. Hunan Cancer Hospital, Changsha, China. 5. The Affiliated Hospital of Medical College, Qingdao University, Qingdao, China. 6. Liaoning Cancer Hospital, Shenyang, China. 7. Fujian Medical University Union Hospital, Fuzhou, China. 8. Jilin Provincial Cancer Hospital, Changchun, China. 9. Jiangsu Cancer Hospital, Nanjing, China. 10. The People's Hospital of Peking University, Beijing, China. 11. Shanghai Pulmonary Hospital, Shanghai, China. 12. Tangdu Hospital, Xi'an, China. 13. Peking University First Hospital, Beijing, China. 14. Fujian Cancer Hospital, Fuzhou, China. 15. Beijing Chest Hospital, Beijing, China. 16. The First Hospital of China Medical University, Shenyang, China. 17. Beijing Cancer Hospital, Beijing, China. 18. The Affiliated Tumor Hospital of Harbin Medical University, Harbin, China. 19. West China Hospital of Sichuan University, Chengdu, China. 20. Sichuan Cancer Hospital, Chengdu, China. 21. The Northern Jiangsu People's Hospital, Yangzhou, China. 22. The First Affiliated Hospital of Suzhou University, Suzhou, China. 23. Guangdong Lung Cancer Institute, Guangdong General Hospital & Guangdong Academy of Medical Sciences, Guangzhou, China. Electronic address: syylwu@live.cn.
Abstract
INTRODUCTION:Adjuvant gefitinib therapy prolonged disease-free survival in patients with resected early-stage EGFR-mutation positive NSCLC in the ADJUVANT study (CTONG 1104). However, treatment failure patterns after gefitinib therapy are less well characterized. METHODS: Overall, 222 stage N1-N2, EGFR-mutant NSCLC patients received gefitinib or vinorelbine plus cisplatin (VP) treatment. Tumor recurrences or metastases occurring during follow-up were defined as treatment failure; sites and data of first treatment failure were recorded. A post hoc analysis of treatment failure patterns which was estimated by Kaplan-Meier and hazard rate curves in modified intention-to-treat patients was conducted. RESULTS: There were 114 recurrences and 10 deaths before recurrence across 124 progression events. Spatial distribution analysis showed that the first metastasis site was most frequently the central nervous system in the gefitinib group (29 of 106 [27.4%]), extracranial metastases were most frequent in the VP group (32 of 87 [36.8%]). Temporal distribution analysis showed lower tumor recurrence with gefitinib than with VP 0 to 21 months post-surgery. However, recurrence with gefitinib showed a constant rate of increase 12 months post-surgery. The first peak of extracranial metastasis appeared during 9 to 15 months with VP and 24 to 30 months with gefitinib. The highest peak for central nervous system metastases post-surgery occurred after 12 to 18 months with VP and 24 to 36 months with gefitinib. CONCLUSIONS:Adjuvant gefitinib showed advantages over VP chemotherapy in treatment failure patterns especially in extracranial metastasis. Adjuvant tyrosine kinas inhibitors may be considered as a treatment option in resected stage N1-N2 EGFR-mutant NSCLC but longer duration should be explored.
RCT Entities:
INTRODUCTION: Adjuvant gefitinib therapy prolonged disease-free survival in patients with resected early-stage EGFR-mutation positive NSCLC in the ADJUVANT study (CTONG 1104). However, treatment failure patterns after gefitinib therapy are less well characterized. METHODS: Overall, 222 stage N1-N2, EGFR-mutant NSCLCpatients received gefitinib or vinorelbine plus cisplatin (VP) treatment. Tumor recurrences or metastases occurring during follow-up were defined as treatment failure; sites and data of first treatment failure were recorded. A post hoc analysis of treatment failure patterns which was estimated by Kaplan-Meier and hazard rate curves in modified intention-to-treat patients was conducted. RESULTS: There were 114 recurrences and 10 deaths before recurrence across 124 progression events. Spatial distribution analysis showed that the first metastasis site was most frequently the central nervous system in the gefitinib group (29 of 106 [27.4%]), extracranial metastases were most frequent in the VP group (32 of 87 [36.8%]). Temporal distribution analysis showed lower tumor recurrence with gefitinib than with VP 0 to 21 months post-surgery. However, recurrence with gefitinib showed a constant rate of increase 12 months post-surgery. The first peak of extracranial metastasis appeared during 9 to 15 months with VP and 24 to 30 months with gefitinib. The highest peak for central nervous system metastases post-surgery occurred after 12 to 18 months with VP and 24 to 36 months with gefitinib. CONCLUSIONS: Adjuvant gefitinib showed advantages over VP chemotherapy in treatment failure patterns especially in extracranial metastasis. Adjuvant tyrosine kinas inhibitors may be considered as a treatment option in resected stage N1-N2 EGFR-mutant NSCLC but longer duration should be explored.
Authors: Annemarie F Shepherd; Isabel R Preeshagul; Narek Shaverdian; Abraham J Wu; Daphna Y Gelblum; Daniel R Gomez; Andreas Rimner; Charles B Simone Journal: Ann Transl Med Date: 2020-12