Efficacy and safety of afatinib in the treatment of advanced non-small cell lung cancer: a systematic review_Chinese Journal of Evidence-Based Medicine

Authors：

LI Qian ¹ , LI Xiao ¹ , LI Ying ¹ , AN Jing ² , QIU Xuejia ² , MA Yinling ² ,  DONG Zhanjun ²

1. Graduate School of Hebei Medical University, Shijiazhuang, 050017, P.R.China;
2. Department of Pharmacy, Hebei Provincial People's Hosiptal, Shijiazhuang, 050051, P.R.China;

Corresponding author：

DONG Zhanjun, Email: 13313213656@126.com

Keywords：

Afatinib; Non-small cell lung cancer; Systematic review; Randomized controlled trial; Meta-analysis

DOI：

10.7507/1672-2531.201702003

Video：

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ObjectiveTo systematically review the clinical efficacy and safety of afatinib in the treatment of advanced non-small cell lung cancer (NSCLC).MethodsWe electronically searched databases including The Cochrane Library, PubMed, EMbase, CNKI, WanFang Data and VIP to collect randomized controlled trials (RCTs) about the afatinib for advanced non-small cell lung cancer from inception to October 2016. Two reviewers independently screened literature, extracted data and assessed the risk of bias of included studies. Then, meta-analysis was performed using RevMan 5.3 software. ResultsEight RCTs were included. The results of meta-analysis showed that afatinib could significantly prolonged progression-free survival (PFS) for lung adenocarcinoma patients (HR=0.43, 95%CI 0.32 to 0.57, P<0.000 01), but there was no significant difference between the two groups in terms of overall survival (OS) in patients with lung adenocarcinoma (HR=1.03, 95%CI 0.85 to 1.23, P=0.79). In addition, afatinib significantly increased the patient’s adverse reactions including diarrhea, skin rashes, nausea and vomiting.ConclusionAfatinib can improve PFS in patients with lung adenocarcinoma, but it does not prolong OS. Due to the limited quantity and quality of included studies, the above conclusions are still needed to be verified by more high quality studies.

Citation： LI Qian, LI Xiao, LI Ying, AN Jing, QIU Xuejia, MA Yinling, DONG Zhanjun. Efficacy and safety of afatinib in the treatment of advanced non-small cell lung cancer: a systematic review. Chinese Journal of Evidence-Based Medicine, 2017, 17(8): 928-933. doi: 10.7507/1672-2531.201702003 Copy

1.	D’Angelo SP, Pietanza MC, Johnson ML, et al. Incidence of EGFR exon 19 deletions and L858R in tumor specimens from men and cigarette smokers with lung adenocarcinomas. J Clin Oncol, 2011, 29(15): 2066-2070.
2.	Shi Y, Au JS, Thongprasert S, et al. A prospective, molecular epidemiology study of EGFR mutations in Asian patients with advanced non-small-cell lung cancer of adenocarcinoma histology (PIONEER). J Thorac Oncol, 2014, 9(2): 154-162.
3.	Shi YK, Li J, Zhang S, et al. Molecular Epidemiology of EGFR mutations in asian patients with advanced non-small-cell lung cancer of adenocarcinoma histology-Mainland China subset analysis of the PIONEER study. PLoS One, 2015, 10(11): e0143515.
4.	罗华婷, 刘锐, 陈川, 等. 阿法替尼治疗 EGFR 突变型晚期非小细胞肺癌的有效性及安全性的研究. 肿瘤药学, 2015, 5(6): 466-471.
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6.	Schuler M, Yang JC, Park K, et al. Afatinib beyond progression in patients with non-small-cell lung cancer following chemotherapy, erlotinib/gefitinib and afatinib: phase III randomized LUX-Lung 5 trial. Ann Oncol, 2016, 27(3): 417-423.
7.	Miller VA, Hirsh V, Cadranel J, et al. Afatinib versus placebo for patients with advanced, metastatic non-small-cell lung cancer after failure of erlotinib, gefitinib, or both, and one or two lines of chemotherapy (LUX-Lung 1): a phase 2b/3 randomised trial. The Lancet Oncology. 2012, 13(5): 528-538.
8.	Sequist LV, Yang JC, Yamamoto N, et al. Phase III study of afatinib or cisplatin plus pemetrexed in patients with metastatic lung adenocarcinoma with EGFR mutations. J Clin Oncol, 2013, 31(27): 3327-3334.
9.	Wu YL, Zhou C, Hu CP, et al. Afatinib versus cisplatin plus gemcitabine for first-line treatment of Asian patients with advanced non-small-cell lung cancer harbouring EGFR mutations (LUX-Lung 6): an open-label, randomised phase 3 trial. The Lancet Oncology, 2014, 15(2): 213-222.
10.	Kato T, Yoshioka H, Okamoto I, et al. Afatinib versus cisplatin plus pemetrexed in Japanese patients with advanced non-small cell lung cancer harboring activating EGFR mutations: subgroup analysis of LUX-Lung 3. Cancer science, 2015, 106(9): 1202-1211.
11.	Machiels JP, Haddad RI, Fayette J, et al. Afatinib versus methotrexate as second-line treatment in patients with recurrent or metastatic squamous-cell carcinoma of the head and neck progressing on or after platinum-based therapy (LUX-Head & Neck 1): an open-label, randomised phase 3 trial. The Lancet Oncology, 2015, 16(5): 583-594.
12.	Soria JC, Felip E, Cobo M, et al. Afatinib versus erlotinib as second-line treatment of patients with advanced squamous cell carcinoma of the lung (LUX-Lung 8): an open-label randomised controlled phase 3 trial. The Lancet Oncology, 2015, 16(8): 897-907.
13.	Park K, Tan E-H, O’Byrne K, et al. Afatinib versus gefitinib as first-line treatment of patients with EGFR mutation-positive non-small-cell lung cancer (LUX-Lung 7): a phase 2B, open-label, randomised controlled trial. The Lancet Oncology, 2016, 17(5): 577-589.
14.	Katakami N, Atagi S, Goto K, et al. LUX-Lung 4: a phase II trial of afatinib in patients with advanced non-small-cell lung cancer who progressed during prior treatment with erlotinib, gefitinib, or both. J Clin Oncol, 2013, 31(27): 3327-3342.
15.	Yang JC, Hirsh V, Schuler M, et al. Symptom control and quality of life in LUX-Lung 3: a phase III study of afatinib or cisplatin/pemetrexed in patients with advanced lung adenocarcinoma with EGFR mutations. J Clin Oncol, 2013, 31(27): 3342-3350.
16.	Geater SL, Xu CR, Zhou C, et al. Symptom and quality of life improvement in LUX-Lung 6: an open-label phase III study of afatinib versus cisplatin/gemcitabine in Asian patients with EGFR mutation-positive advanced non-small-cell lung cancer. J Thorac Oncol, 2015, 10(6): 883-889.
17.	Schuler M, Wu YL, Hirsh V, et al. First-line afatinib versus chemotherapy in patients with non-small cell lung cancer and common epidermal growth factor receptor gene mutations and brain metastases. J Thorac Oncol, 2016, 11(3): 380-390.
18.	赵明芳, 刘云鹏, 娄娜娜. LUX-Lung 6 研究引发的 EGFR-TKI 治疗 19 Del 和 L858R 突变晚期非小细胞肺癌疗效探讨. 循证医学, 2015, 15(1): 37-41.
19.	Lee VH, Leung DK, Choy TS, et al. Efficacy and safety of afatinib in Chinese patients with EGFR-mutated metastatic non-small-cell lung cancer (NSCLC) previously responsive to first-generation tyrosine-kinase inhibitors (TKI) and chemotherapy: comparison with historical cohort using erlotinib. BMC cancer, 2016, 16: 147.
20.	Hirsh V, Cadranel J, Cong XJ, et al. Symptom and quality of life benefit of afatinib in advanced non-small-cell lung cancer patients previously treated with erlotinib or gefitinib: results of a randomized phase IIb/III trial (LUX-Lung 1). J Thorac Oncol, 2013, 8(2): 229-237.

1. D’Angelo SP, Pietanza MC, Johnson ML, et al. Incidence of EGFR exon 19 deletions and L858R in tumor specimens from men and cigarette smokers with lung adenocarcinomas. J Clin Oncol, 2011, 29(15): 2066-2070.
2. Shi Y, Au JS, Thongprasert S, et al. A prospective, molecular epidemiology study of EGFR mutations in Asian patients with advanced non-small-cell lung cancer of adenocarcinoma histology (PIONEER). J Thorac Oncol, 2014, 9(2): 154-162.
3. Shi YK, Li J, Zhang S, et al. Molecular Epidemiology of EGFR mutations in asian patients with advanced non-small-cell lung cancer of adenocarcinoma histology-Mainland China subset analysis of the PIONEER study. PLoS One, 2015, 10(11): e0143515.
4. 罗华婷, 刘锐, 陈川, 等. 阿法替尼治疗 EGFR 突变型晚期非小细胞肺癌的有效性及安全性的研究. 肿瘤药学, 2015, 5(6): 466-471.
5. 李静, 张鸣明. Cochrane 干预措施系统评价手册. 四川大学华西医院中国 Cochrane 中心, 兰州大学循证医学中心, 2014: 174-219.
6. Schuler M, Yang JC, Park K, et al. Afatinib beyond progression in patients with non-small-cell lung cancer following chemotherapy, erlotinib/gefitinib and afatinib: phase III randomized LUX-Lung 5 trial. Ann Oncol, 2016, 27(3): 417-423.
7. Miller VA, Hirsh V, Cadranel J, et al. Afatinib versus placebo for patients with advanced, metastatic non-small-cell lung cancer after failure of erlotinib, gefitinib, or both, and one or two lines of chemotherapy (LUX-Lung 1): a phase 2b/3 randomised trial. The Lancet Oncology. 2012, 13(5): 528-538.
8. Sequist LV, Yang JC, Yamamoto N, et al. Phase III study of afatinib or cisplatin plus pemetrexed in patients with metastatic lung adenocarcinoma with EGFR mutations. J Clin Oncol, 2013, 31(27): 3327-3334.
9. Wu YL, Zhou C, Hu CP, et al. Afatinib versus cisplatin plus gemcitabine for first-line treatment of Asian patients with advanced non-small-cell lung cancer harbouring EGFR mutations (LUX-Lung 6): an open-label, randomised phase 3 trial. The Lancet Oncology, 2014, 15(2): 213-222.
10. Kato T, Yoshioka H, Okamoto I, et al. Afatinib versus cisplatin plus pemetrexed in Japanese patients with advanced non-small cell lung cancer harboring activating EGFR mutations: subgroup analysis of LUX-Lung 3. Cancer science, 2015, 106(9): 1202-1211.
11. Machiels JP, Haddad RI, Fayette J, et al. Afatinib versus methotrexate as second-line treatment in patients with recurrent or metastatic squamous-cell carcinoma of the head and neck progressing on or after platinum-based therapy (LUX-Head & Neck 1): an open-label, randomised phase 3 trial. The Lancet Oncology, 2015, 16(5): 583-594.
12. Soria JC, Felip E, Cobo M, et al. Afatinib versus erlotinib as second-line treatment of patients with advanced squamous cell carcinoma of the lung (LUX-Lung 8): an open-label randomised controlled phase 3 trial. The Lancet Oncology, 2015, 16(8): 897-907.
13. Park K, Tan E-H, O’Byrne K, et al. Afatinib versus gefitinib as first-line treatment of patients with EGFR mutation-positive non-small-cell lung cancer (LUX-Lung 7): a phase 2B, open-label, randomised controlled trial. The Lancet Oncology, 2016, 17(5): 577-589.
14. Katakami N, Atagi S, Goto K, et al. LUX-Lung 4: a phase II trial of afatinib in patients with advanced non-small-cell lung cancer who progressed during prior treatment with erlotinib, gefitinib, or both. J Clin Oncol, 2013, 31(27): 3327-3342.
15. Yang JC, Hirsh V, Schuler M, et al. Symptom control and quality of life in LUX-Lung 3: a phase III study of afatinib or cisplatin/pemetrexed in patients with advanced lung adenocarcinoma with EGFR mutations. J Clin Oncol, 2013, 31(27): 3342-3350.
16. Geater SL, Xu CR, Zhou C, et al. Symptom and quality of life improvement in LUX-Lung 6: an open-label phase III study of afatinib versus cisplatin/gemcitabine in Asian patients with EGFR mutation-positive advanced non-small-cell lung cancer. J Thorac Oncol, 2015, 10(6): 883-889.
17. Schuler M, Wu YL, Hirsh V, et al. First-line afatinib versus chemotherapy in patients with non-small cell lung cancer and common epidermal growth factor receptor gene mutations and brain metastases. J Thorac Oncol, 2016, 11(3): 380-390.
18. 赵明芳, 刘云鹏, 娄娜娜. LUX-Lung 6 研究引发的 EGFR-TKI 治疗 19 Del 和 L858R 突变晚期非小细胞肺癌疗效探讨. 循证医学, 2015, 15(1): 37-41.
19. Lee VH, Leung DK, Choy TS, et al. Efficacy and safety of afatinib in Chinese patients with EGFR-mutated metastatic non-small-cell lung cancer (NSCLC) previously responsive to first-generation tyrosine-kinase inhibitors (TKI) and chemotherapy: comparison with historical cohort using erlotinib. BMC cancer, 2016, 16: 147.
20. Hirsh V, Cadranel J, Cong XJ, et al. Symptom and quality of life benefit of afatinib in advanced non-small-cell lung cancer patients previously treated with erlotinib or gefitinib: results of a randomized phase IIb/III trial (LUX-Lung 1). J Thorac Oncol, 2013, 8(2): 229-237.

Chinese Journal of Evidence-Based Medicine

Efficacy and safety of afatinib in the treatment of advanced non-small cell lung cancer: a systematic review

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