Research article Special Issues

The efficacy and safety of erlotinib compared with chemotherapy in previously treated NSCLC: A meta-analysis

  • Received: 20 February 2019 Accepted: 10 July 2019 Published: 28 August 2019
  • BackgroundAn increasing number of patients with advanced non-small cell lung cancer (NSCLC) have a poor prognosis and develop progressive disease after receiving conventional treatments. In recent years, several novel therapies have been approved for later lines of therapy of previously treated NSCLC. Erlotinib, an EGFR tyrosine kinase inhibitor, was recommended as the second-line therapy for pre-treated patients. However, the use of erlotinib has been reported to represent different clinical effects and adverse effects.
    ObjectivesThe current study was aim to investigate the efficacy and safety of erlotinib versus chemotherapy in pre-treated patients with advanced NSCLC.
    MethodsElectronic databases were searched for eligible literatures updated on June 2018. Randomized-controlled trials assessing the efficacy and safety of erlotinib in pre-treated NSCLC were included, of which the main outcomes were ORR (objective response rate), PFS (progression-free survival), OS (overall survival) and AEs (adverse events). All the data were pooled with the corresponding 95% confidence interval using RevMan software. Sensitivity analyses and heterogeneity were quantitatively evaluated.
    ResultsA total of 11 randomized controlled trials were included in this analysis. The group of erlotinib did not achieved benefit in progression-free survival (OR = 0.61, 95%CI = 0.33–1.12, P = 0.11), overall survival (OR = 0.98, 95%CI = 0.84–1.15, P = 0.81) as well with the objective response rate (OR = 0.77, 95%CI = 0.36–1.63, P = 0.49), respectively. In the results of subgroup analysis among the patients with EGFR wild-type, there is also no significant differences in overall survival with erlotinib (OR = 0.90, 95%CI = 0.78–1.04, P = 0.15) and progression-free survival (OR = 0.33, 95%CI = 0.09–1.18, P = 0.09). The most common treatment-related adverse events in the erlotinib group is rash (OR = 5.79, 95%CI = 2.12–15.77, P = 0.0006), and neutropenia (OR = 0.02, 95%CI = 0.01–0.10, P ≤ 0.00001) is more found in the control group. In addition, fatigue (P = 0.09) and diarrhea (P = 0.52), the difference between the two groups had no statistical significance.
    ConclusionsThere was no significant difference noted with regard to efficacy and safety between erlotinib vs. chemotherapy as the later-line therapy for previously treated patients with NSCLC, even with subgroup patients who have wild-type EGFR tumors. While, erlotinib might increase the risk of rash, and decrease the risk of neutropenia, compared with the chemotherapy. Further research is needed to develop a database of all EGFR mutations and their individual impact on the differing treatments.

    Citation: Fazong Wu, Jingjing Song, Zhongwei Zhao, Xufang Huang, Jianting Mao, Jianfei Tu, Minjiang Chen, Weiqian Chen, Shiji Fang, Liyun Zheng, Xiaoxi Fan. The efficacy and safety of erlotinib compared with chemotherapy in previously treated NSCLC: A meta-analysis[J]. Mathematical Biosciences and Engineering, 2019, 16(6): 7921-7933. doi: 10.3934/mbe.2019398

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  • BackgroundAn increasing number of patients with advanced non-small cell lung cancer (NSCLC) have a poor prognosis and develop progressive disease after receiving conventional treatments. In recent years, several novel therapies have been approved for later lines of therapy of previously treated NSCLC. Erlotinib, an EGFR tyrosine kinase inhibitor, was recommended as the second-line therapy for pre-treated patients. However, the use of erlotinib has been reported to represent different clinical effects and adverse effects.
    ObjectivesThe current study was aim to investigate the efficacy and safety of erlotinib versus chemotherapy in pre-treated patients with advanced NSCLC.
    MethodsElectronic databases were searched for eligible literatures updated on June 2018. Randomized-controlled trials assessing the efficacy and safety of erlotinib in pre-treated NSCLC were included, of which the main outcomes were ORR (objective response rate), PFS (progression-free survival), OS (overall survival) and AEs (adverse events). All the data were pooled with the corresponding 95% confidence interval using RevMan software. Sensitivity analyses and heterogeneity were quantitatively evaluated.
    ResultsA total of 11 randomized controlled trials were included in this analysis. The group of erlotinib did not achieved benefit in progression-free survival (OR = 0.61, 95%CI = 0.33–1.12, P = 0.11), overall survival (OR = 0.98, 95%CI = 0.84–1.15, P = 0.81) as well with the objective response rate (OR = 0.77, 95%CI = 0.36–1.63, P = 0.49), respectively. In the results of subgroup analysis among the patients with EGFR wild-type, there is also no significant differences in overall survival with erlotinib (OR = 0.90, 95%CI = 0.78–1.04, P = 0.15) and progression-free survival (OR = 0.33, 95%CI = 0.09–1.18, P = 0.09). The most common treatment-related adverse events in the erlotinib group is rash (OR = 5.79, 95%CI = 2.12–15.77, P = 0.0006), and neutropenia (OR = 0.02, 95%CI = 0.01–0.10, P ≤ 0.00001) is more found in the control group. In addition, fatigue (P = 0.09) and diarrhea (P = 0.52), the difference between the two groups had no statistical significance.
    ConclusionsThere was no significant difference noted with regard to efficacy and safety between erlotinib vs. chemotherapy as the later-line therapy for previously treated patients with NSCLC, even with subgroup patients who have wild-type EGFR tumors. While, erlotinib might increase the risk of rash, and decrease the risk of neutropenia, compared with the chemotherapy. Further research is needed to develop a database of all EGFR mutations and their individual impact on the differing treatments.


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    [1] L. A. Torre, F. Bray, R. L. Siegel, et al., Global cancer statistics, 2012, CA-Cancer J. Clin., 65 (2015), 87–108.
    [2] S. K. Alpard and J. B. Zwischenberger, Staging and surgery for non-small cell lung cancer (NSCLC), Surg. Oncol., 7 (1998), 25–43.
    [3] A. P. Abernethy, A. Arunachalam, T. Burke, et al., Real-world first-line treatment and overall survival in non-small cell lung cancer without known EGFR mutations or ALK rearrangements in US community oncology setting, PLoS One, 12 (2017), e0178420.
    [4] J. Davies, M. Patel, C. Gridelli, et al., Real-world treatment patterns for patients receiving second-line and third-line treatment for advanced non-small cell lung cancer: A systematic review of recently published studies, PLoS One, 12 (2017), e0175679.
    [5] F. Aguiar, G. Fernandes, H. Queiroga, et al., Overall survival analysis and characterization of an egfr mutated non-small cell lung cancer (NSCLC) population, Arch. Bronconeumol., 54 (2018), 10–17.
    [6] F. A. Shepherd, J. Dancey, R. Ramlau, et al., Prospective randomized trial of docetaxel versus best supportive care in patients with non-small-cell lung cancer previously treated with platinum-based chemotherapy, J. Clin. Oncol., 18 (2000), 2095–2103.
    [7] F. V. Fossella, R. DeVore, R. N. Kerr, et al., Randomized phase III trial of docetaxel versus vinorelbine or ifosfamide in patients with advanced non-small-cell lung cancer previously treated with platinum-containing chemotherapy regimens. The TAX 320 Non-Small Cell Lung Cancer Study Group, J. Clin. Oncol., 18 (2000), 2354–2362.
    [8] N. Hanna, F. A. Shepherd, F. V. Fossella, et al., Randomized phase III trial of pemetrexed versus docetaxel in patients with non-small-cell lung cancer previously treated with chemotherapy, J. Clin. Oncol., 22 (2004), 1589–1597.
    [9] J. C. Soria, E. Felip, M. Cobo, 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, Lancet Oncol., 16 (2015), 897–907.
    [10] I. Okamoto, H. Yoshioka, S. Morita, et al., Phase III trial comparing oral S-1 plus carboplatin with paclitaxel plus carboplatin in chemotherapy-naive patients with advanced non-small-cell lung cancer: results of a west Japan oncology group study, J. Clin. Oncol., 28 (2010), 5240–5246.
    [11] Y. Totani, Y. Saito, M. Hayashi, et al., A phase II study of S-1 monotherapy as second-line treatment for advanced non-small cell lung cancer, Cancer Chemother. Pharmacol., 64 (2009), 1181–1185.
    [12] Comprehensive molecular profiling of lung adenocarcinoma, Nature, 511 (2014), 543–550.
    [13] L. M. Sholl, D. L. Aisner, M. Varella-Garcia, et al., Multi-institutional oncogenic driver mutation analysis in lung adenocarcinoma: The lung cancer mutation consortium experience, J. Thorac. Oncol., 10 (2015), 768–777.
    [14] T. S. Mok, Y. L. Wu, S. Thongprasert, et al., Gefitinib or carboplatin-paclitaxel in pulmonary adenocarcinoma, N. Engl. J. Med., 361 (2009), 947–957.
    [15] R. Rosell, E. Carcereny, R. Gervais, et al., Erlotinib versus standard chemotherapy as first-line treatment for European patients with advanced EGFR mutation-positive non-small-cell lung cancer (EURTAC): A multicentre, open-label, randomised phase 3 trial, Lancet Oncol., 13 (2012), 239–246.
    [16] R. S. Herbst and P. A. Bunn, Jr., Targeting the epidermal growth factor receptor in non-small cell lung cancer, Clin. Cancer Res., 9 (2003), 5813–5824.
    [17] M. H. Cohen, J. R. Johnson, Y. F. Chen, et al., FDA drug approval summary: Erlotinib (Tarceva) tablets, Oncologist, 10 (2005), 461–466.
    [18] J. J. Yang, Q. Zhou, H. H. Yan, et al., A phase III randomised controlled trial of erlotinib vs. gefitinib in advanced non-small cell lung cancer with EGFR mutations, Br. J. Cancer, 116 (2017), 568–574.
    [19] H. Borghaei, L. Paz-Ares, L. Horn, et al., Nivolumab versus Docetaxel in Advanced Nonsquamous Non-Small-Cell Lung Cancer, N. Engl. J. Med., 373 (2015), 1627–1639.
    [20] A. R. Jadad, R. A. Moore, D. Carroll, et al., Assessing the quality of reports of randomized clinical trials: is blinding necessary?, Control Clin. Trials., 17 (1996), 1–12.
    [21] J. P. Higgins and S. G. Thompson, Quantifying heterogeneity in a meta-analysis, Stat. Med., 21 (2002), 1539–1558.
    [22] J. P. Higgins, S. G. Thompson, J. J. Deeks, et al., Measuring inconsistency in meta-analyses, BMJ, 327 (2003), 557–560.
    [23] O. Fiala, M. Pesek, J. Finek, et al., Pemetrexed versus erlotinib in the second-line treatment of patients with advanced-stage non-squamous NSCLC harboring wild-type EGFR gene, Anticancer Res., 36 (2016), 447–453.
    [24] N. Li, W. Ou, H. Yang, et al., A randomized phase 2 trial of erlotinib versus pemetrexed as second-line therapy in the treatment of patients with advanced EGFR wild-type and EGFR FISH-positive lung adenocarcinoma, Cancer, 120 (2014), 1379–1386.
    [25] D. H. Lee, J. S. Lee, S. W. Kim, et al., Three-arm randomised controlled phase 2 study comparing pemetrexed and erlotinib to either pemetrexed or erlotinib alone as second-line treatment for never-smokers with non-squamous non-small cell lung cancer, Eur. J. Cancer, 49 (2013), 3111–3121.
    [26] A. Karampeazis, A. Voutsina, J. Souglakos, et al., Pemetrexed versus erlotinib in pretreated patients with advanced non-small cell lung cancer: A Hellenic Oncology Research Group (HORG) randomized phase 3 study, Cancer, 119 (2013), 2754–2764.
    [27] F. Koinis, S. Agelaki, V. Karavassilis, et al., Second-line pazopanib in patients with relapsed and refractory small-cell lung cancer: A multicentre phase II study of the Hellenic Oncology Research Group, Br. J. Cancer, 117 (2017), 8–14.
    [28] T. Ciuleanu, L. Stelmakh, S. Cicenas, et al., Efficacy and safety of erlotinib versus chemotherapy in second-line treatment of patients with advanced, non-small-cell lung cancer with poor prognosis (TITAN): a randomised multicentre, open-label, phase 3 study, Lancet Oncol., 13 (2012), 300–308.
    [29] V. Gregorc, S. Novello, C. Lazzari, et al., Predictive value of a proteomic signature in patients with non-small-cell lung cancer treated with second-line erlotinib or chemotherapy (PROSE): A biomarker-stratified, randomised phase 3 trial, Lancet Oncol., 15 (2014), 713–721.
    [30] Y. Ikezawa, H. Asahina, S. Oizumi, et al., A randomized phase II trial of erlotinib vs. S-1 as a third- or fourth-line therapy for patients with wild-type EGFR non-small cell lung cancer (HOT1002), Cancer Chemother. Pharmacol., 80 (2017), 955–963.
    [31] S. Peters, R. A. Stahel, U. Dafni, et al., Randomized phase III trial of erlotinib versus docetaxel in patients with advanced squamous cell non-small cell lung cancer failing first-line platinum-based doublet chemotherapy stratified by veristrat good versus veristrat poor. the european thoracic oncology platform (ETOP) EMPHASIS-lung trial, J. Thorac. Oncol., 12 (2017), 752–762.
    [32] T. Kawaguchi, M. Ando, K. Asami, et al., Randomized phase III trial of erlotinib versus docetaxel as second- or third-line therapy in patients with advanced non-small-cell lung cancer: Docetaxel and Erlotinib Lung Cancer Trial (DELTA), J. Clin. Oncol., 32 (2014), 1902–1908.
    [33] J. R. Molina, P. Yang, S. D. Cassivi, et al., Non-small cell lung cancer: epidemiology, risk factors, treatment, and survivorship, Mayo Clin. Proc., 83 (2008), 584–594.
    [34] D. S. Ettinger, W. Akerley, H. Borghaei, et al., Non-small cell lung cancer, version 2.2013, J. Natl. Compr. Canc. Netw., 11 (2013), 645–653.
    [35] F. A. Shepherd, J. Rodrigues Pereira, T. Ciuleanu, et al., Erlotinib in previously treated non-small-cell lung cancer, N. Engl. J. Med., 353 (2005), 123–132.
    [36] M. C. Garassino, S. Marsoni and I. Floriani, Testing epidermal growth factor receptor mutations in patients with non-small-cell lung cancer to choose chemotherapy: The other side of the coin, J. Clin. Oncol., 29 (2011), 3835–3837; author reply 3837–3839.
    [37] S. A. Laurie and G. D. Goss, Role of epidermal growth factor receptor inhibitors in epidermal growth factor receptor wild-type non-small-cell lung cancer, J. Clin. Oncol., 31 (2013), 1061–-1069.
    [38] C. P. Schneider, D. Heigener, K. Schott-von-Romer, et al., Epidermal growth factor receptor-related tumor markers and clinical outcomes with erlotinib in non-small cell lung cancer: an analysis of patients from german centers in the TRUST study, J. Thorac. Oncol., 3 (2008), 1446–1453.
    [39] J. Y. Douillard, F. A. Shepherd, V. Hirsh, et al., Molecular predictors of outcome with gefitinib and docetaxel in previously treated non-small-cell lung cancer: data from the randomized phase III INTEREST trial, J. Clin. Oncol., 28 (2010), 744–752.
    [40] M. Maemondo, A. Inoue, K. Kobayashi, et al., Gefitinib or chemotherapy for non-small-cell lung cancer with mutated EGFR, N. Engl. J. Med., 362 (2010), 2380–2388.
    [41] T. Mitsudomi, S. Morita, Y. Yatabe, et al., Gefitinib versus cisplatin plus docetaxel in patients with non-small-cell lung cancer harbouring mutations of the epidermal growth factor receptor (WJTOG3405): An open label, randomised phase 3 trial, Lancet Oncol., 11 (2010), 121–128.
    [42] R. Rosell, T. Moran, C. Queralt, et al., Screening for epidermal growth factor receptor mutations in lung cancer, N. Engl. J. Med., 361 (2009), 958–967.
    [43] L. V. Sequist, J. C. Yang, N. Yamamoto, et al., Phase III study of afatinib or cisplatin plus pemetrexed in patients with metastatic lung adenocarcinoma with EGFR mutations, J. Clin. Oncol., 31 (2013), 3327–3334.
    [44] Y. Li, T. Cheng, L. Chen, et al., Erlotinib versus chemotherapy (Docetaxel/pemetrexed) as second-line therapy in advanced non-small cell lung cancer: A meta-analysis, Int. J. Clin. Exp. Med., 10 (2017), 4606–4617.
    [45] H. Linardou, I. J. Dahabreh, D. Kanaloupiti, et al., Assessment of somatic k-RAS mutations as a mechanism associated with resistance to EGFR-targeted agents: A systematic review and meta-analysis of studies in advanced non-small-cell lung cancer and metastatic colorectal cancer, Lancet Oncol., 9 (2008), 962–972.
    [46] C. Mao, L. X. Qiu, R. Y. Liao, et al., KRAS mutations and resistance to EGFR-TKIs treatment in patients with non-small cell lung cancer: A meta-analysis of 22 studies, Lung Cancer, 69 (2010), 272–278.
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