Wenjie Tang1, Xiaolin Li2, Xueqi Xie3, Xindong Sun2, Jie Liu4, Jian Zhang5, Chungang Wang6, Jinming Yu7, Peng Xie8. 1. School of Medicine and Life Sciences, University of Jinan-Shandong Academy of Medical Sciences, Jinan, Shandong 250117, China; Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong 250117, China. 2. Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong 250117, China. 3. School of Medicine and Life Sciences, Shandong First Medical University, Jinan, Shandong 250117, China. 4. Department of Thoracic Surgery, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong 250117, China. 5. Department of Respiratory Medicine, Linshu People's Hospital, Linyi, Shandong 276700, China. 6. Department of Medical Oncology, Lingcheng People's Hospital, Dezhou, Shandong 253500, China. 7. Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong 250117, China. Electronic address: sdyujinming@163.com. 8. Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong 250117, China. Electronic address: xiepengro@126.com.
Abstract
OBJECTIVES: Cisplatin-based chemotherapy as an adjuvant therapy for resected non-small cell lung cancer (NSCLC) has reached its plateau, and it is limited by a high risk of recurrence and significant toxicities. The clinical value of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) in resected NSCLC harboring EGFR mutations remains controversial. In this study, we performed a meta-analysis to evaluate the role of EGFR inhibitors as an adjuvant therapy for targeted patients. MATERIALS AND METHODS: Studies were identified via electronic search. The pooled odds ratio (OR) for disease-free survival (DFS) and overall survival (OS) were calculated for the meta-analysis. RESULTS: There were 11 trials (1,152 resected NSCLC patients with EGFR sensitive mutations) in this meta-analysis. The results showed that adjuvant treatment with EGFR-TKIs can prolong both the OS and DFS when compared to treatment without TKIs as an adjuvant therapy (OS: OR, 0.63; 95% CI, 0.46 to 0.87, P = 0.004; heterogeneity I2 = 61%, P = 0.008; DFS: OR, 0.56; 95% CI, 0.43 to 0.72, P < 0.00001; heterogeneity I2 = 37%, P = 0.10). The results of the predefined subgroup analyses in this meta-analysis suggested a greater DFS with the mono EGFR-TKIs compared with chemotherapy, whereas the OS benefit failed to show a similar difference between the two arms (p = 0.30). We also found that treatment with EGFR-TKIs plus chemotherapy was associated with a significantly longer DFS and OS compared to mono chemotherapy in patients with completely resected EGFR-mutant NSCLC (DFS: OR, 0.48; 95% CI, 0.34-0.68; P < 0.0001; heterogeneity I2 = 47%, P = 0.07; OS: OR, 0.50; 95% CI, 0.31-0.78; P = 0.003; heterogeneity I2 = 57%, P = 0.05). Additionally, less severe adverse events (SAEs) were observed in the TKIs group (OR, 0.22; 95% CI, 0.14 to 0.37, P < 0.00001; heterogeneity I2 = 22%, P = 0.28). CONCLUSION: The addition of EGFR-TKIs to adjuvant chemotherapy can prolong the OS and PFS for resected NSCLC. Adjuvant EGFR-TKIs may be a potential treatment option compared to adjuvant chemotherapy in completely resected patients with EGFR mutation-positive NSCLC. STATEMENT OF SIGNIFICANCE: The clinical value of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) in resected non-small cell lung cancer (NSCLC) harboring EGFR mutations remains controversial. This study demonstrates that EGFR-TKIs as an adjuvant therapy could prolong the DFS and potentially prolong the OS in postoperative patients. Therefore, this therapy paves the way for EGFR-TKIs to be an adjuvant treatment for NSCLC.
OBJECTIVES:Cisplatin-based chemotherapy as an adjuvant therapy for resected non-small cell lung cancer (NSCLC) has reached its plateau, and it is limited by a high risk of recurrence and significant toxicities. The clinical value of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) in resected NSCLC harboring EGFR mutations remains controversial. In this study, we performed a meta-analysis to evaluate the role of EGFR inhibitors as an adjuvant therapy for targeted patients. MATERIALS AND METHODS: Studies were identified via electronic search. The pooled odds ratio (OR) for disease-free survival (DFS) and overall survival (OS) were calculated for the meta-analysis. RESULTS: There were 11 trials (1,152 resected NSCLCpatients with EGFR sensitive mutations) in this meta-analysis. The results showed that adjuvant treatment with EGFR-TKIs can prolong both the OS and DFS when compared to treatment without TKIs as an adjuvant therapy (OS: OR, 0.63; 95% CI, 0.46 to 0.87, P = 0.004; heterogeneity I2 = 61%, P = 0.008; DFS: OR, 0.56; 95% CI, 0.43 to 0.72, P < 0.00001; heterogeneity I2 = 37%, P = 0.10). The results of the predefined subgroup analyses in this meta-analysis suggested a greater DFS with the mono EGFR-TKIs compared with chemotherapy, whereas the OS benefit failed to show a similar difference between the two arms (p = 0.30). We also found that treatment with EGFR-TKIs plus chemotherapy was associated with a significantly longer DFS and OS compared to mono chemotherapy in patients with completely resected EGFR-mutant NSCLC (DFS: OR, 0.48; 95% CI, 0.34-0.68; P < 0.0001; heterogeneity I2 = 47%, P = 0.07; OS: OR, 0.50; 95% CI, 0.31-0.78; P = 0.003; heterogeneity I2 = 57%, P = 0.05). Additionally, less severe adverse events (SAEs) were observed in the TKIs group (OR, 0.22; 95% CI, 0.14 to 0.37, P < 0.00001; heterogeneity I2 = 22%, P = 0.28). CONCLUSION: The addition of EGFR-TKIs to adjuvant chemotherapy can prolong the OS and PFS for resected NSCLC. Adjuvant EGFR-TKIs may be a potential treatment option compared to adjuvant chemotherapy in completely resected patients with EGFR mutation-positive NSCLC. STATEMENT OF SIGNIFICANCE: The clinical value of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) in resected non-small cell lung cancer (NSCLC) harboring EGFR mutations remains controversial. This study demonstrates that EGFR-TKIs as an adjuvant therapy could prolong the DFS and potentially prolong the OS in postoperative patients. Therefore, this therapy paves the way for EGFR-TKIs to be an adjuvant treatment for NSCLC.
Authors: Stacyann Bailey; Qian Wang; Chung Yin Kong; Kimberly Stone; Rajwanth Veluswamy; Susan E Bates; Cardinale B Smith; Juan P Wisnivesky; Keith Sigel Journal: Curr Probl Cancer Date: 2022-05-21 Impact factor: 2.367