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Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor Versus Placebo as Maintenance Therapy for Advanced Non-small-cell Lung Cancer: A Meta-analysis of Randomized Controlled Trials

  • Alimujiang, S. (Department of Chemotherapy, Tumor Hospital Affiliated to Xinjiang Medical University) ;
  • Zhang, Tao (Department of Chemotherapy, Tumor Hospital Affiliated to Xinjiang Medical University) ;
  • Han, Zhi-Gang (Department of Chemotherapy, Tumor Hospital Affiliated to Xinjiang Medical University) ;
  • Yuan, Shuai-Fei (Department of Chemotherapy, Tumor Hospital Affiliated to Xinjiang Medical University) ;
  • Wang, Qiang (Department of Chemotherapy, Tumor Hospital Affiliated to Xinjiang Medical University) ;
  • Yu, Ting-Ting (Department of Chemotherapy, Tumor Hospital Affiliated to Xinjiang Medical University) ;
  • Shan, Li (Department of Chemotherapy, Tumor Hospital Affiliated to Xinjiang Medical University)
  • Published : 2013.04.30

Abstract

Background: Use of epidermal growth factor receptor inhibitors (EGFR-TKIs ) is now standard for non-small-cell lung cancer (NSCLC). However, the effects of EGFR-TKIs in maintenance therapy for advanced NSCLC patients are still unclear. The preent meta-analysis was performed to examine pooled data of randomized control trials (RCT) where EGFR-TKIs were compared against placebo in maintenance regimens for patients with advanced NCSLC to quantify potential benefits and determine safety. Methods: Several data bases were searched, including PubMed, EMBASE and CENTRAL, and we performed an internet search of conference literature. The endpoints were objective response rates (ORR), progression-free survival (PFS) and overall survival (OS). We performed a meta-analysis of the published data, using Comprehensive Meta Analysis software (Version 2.0). with a fixed effects model and an additional random effects model, when applicable. The results of the meta-analysis are expressed as hazard ratios (HRs) or risk ratios (RRs), with their corresponding 95% confidence intervals (95%CIs). Results: The final analysis included six trials, covering 3,758 patients. Compared with placebo, EGFR-TKIs maintenance therapy improved ORR and PFS for patients with advanced NSCLC, the difference being statistically significant (P<0.05), but proved unable to prolong patients' OS. The main adverse reactions were diarrhea and rashes. Conclusion: EGFR-TKIs demonstrated encouraging efficacy, safety and survival when delivered as maintenance therapy for patients with advanced NSCLC after first-line chemotherapy, especially for the patients who had adenocarcinomas, were female, non-smokers and patients with EGFR gene mutations.

References

  1. Armijo-Olivo S, Stiles CR, Hagen NA, Biondo PD, Cummings GG (2012). Assessment of study quality for systematic reviews: a comparison of the Cochrane Collaboration Risk of Bias Tool and the Effective Public Health Practice Project Quality Assessment Tool: methodological research. J Eval Clin Pract, 18, 12-8. https://doi.org/10.1111/j.1365-2753.2010.01516.x
  2. Cappuzzo F, Ciuleanu T, Stelmakh L, et al (2010). Erlotinib as maintenance treatment in advanced non-small-cell lung cancer:a multicentre, randomised, placebo cont-rolled phase 3 study. Lancet Oncol, 11, 521-9. https://doi.org/10.1016/S1470-2045(10)70112-1
  3. Ciardiello F, Tortora G (2008). EGFR antagonists in cancer treatment. New Engl J Med, 358, 1160-74. https://doi.org/10.1056/NEJMra0707704
  4. Cohen MH, Johnson JR, Chattopadhyay S,et al (2010). Approval summary: erlotinib maintenance therapy of advanced/ metastatic non-small cell lung cancer (NSCLC). Oncologist, 15, 1344-51. https://doi.org/10.1634/theoncologist.2010-0257
  5. Ferlay J, Shin HR, Bray F, et al (2010). Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer, 127, 2893-917. https://doi.org/10.1002/ijc.25516
  6. Gaafar RM, Surmont VF, Scagliotti GV, et al (2011). A doubleblind, randomised, placebo-controlled phase III intergroup study of gefitinib in patients with advan-ced NSCLC, nonprogressing after first line platinum-based chemotherapy (EORTC 08021/ILCP 01/03). Eur J Cancer, 47, 2331-40. https://doi.org/10.1016/j.ejca.2011.06.045
  7. Galetta D, Rossi A, Pisconti S, Millaku A, Colucci G (2010). Maintenance or non-maintenance therapy in the treatment of advanced non-small cell lung cancer: that is the question. Cancer Treat Rev, 36, 30-3. https://doi.org/10.1016/S0305-7372(10)70017-7
  8. Gatzemeier U, Pluzanska A, Szczesna A, et al (2007). Phase III study of erlotinib in combination with cisplatin and gemcitabine in advanced non-small-cell lung cancer: the Tarceva Lung Cancer Investigation Trial. J Clin Oncol, 25, 1545-52. https://doi.org/10.1200/JCO.2005.05.1474
  9. Grossi F, Aita M, Foilador A, et al (2007). Sequential, alternating, and maintenance /consolidation chemotherapy in advanced non-small cell lung cancer: a review for the literature. Oncologist, 12, 451-64. https://doi.org/10.1634/theoncologist.12-4-451
  10. Herbst RS, Prager D, Hermann R, et al (2005). TRIBUTE: a phase III trial of erlotinib hydrochloride (OSI-774) combined with carboplatin and paclitaxel chemotherapy in advanced non-small-cell lung cancer. J Clin Oncol, 23, 5892-9. https://doi.org/10.1200/JCO.2005.02.840
  11. Inal A, Kaplan MA, Kucukoner M, et al (2012). Prognostic factors for second-line treatment of advanced non-small-cell lung cancer: retrospective analysis at a single institution. Asian Pac J Cancer Prev, 13, 1281-4. https://doi.org/10.7314/APJCP.2012.13.4.1281
  12. Kelly K, Chansky K, Gaspar LE, et al (2008). Phase III trial of maintenance gefitinib or placebo after concurrent chemoradiotherapy and docetaxel consolidation in inoperable stage III non-small-cell lung cancer: SWOG S0023. J Clin Oncol, 26, 2450-6. https://doi.org/10.1200/JCO.2007.14.4824
  13. Lee SM, Khan I, Upadhyay S, et al (2012). First-line erlotinib in patients with advanced non-small-cell lung cancer unsuitable for chemotherapy (TOPICAL): a double-blind, placebocontrolled, phase 3 trial. Lancet Oncol, 13, 1161-70. https://doi.org/10.1016/S1470-2045(12)70412-6
  14. Liu HB, Wu Y, Lv TF, et al (2013). Skin rash could predict the response to EGFR tyrosine kinase inhibitor and the prognosis for patients with non-small cell lung cancer: a systematic review and meta-analysis. PLoS One, 8, e55128. https://doi.org/10.1371/journal.pone.0055128
  15. Lu S, Yu YF (2011). Maintenance Therapy for NSCLC: Consensus and Controversy. Chin J Cancer Res, 23, 254-8. https://doi.org/10.1007/s11670-011-0254-5
  16. Miller VA, O'Connor P, Soh C, et al (2009). For the ATLAS Investigators: A randomized, double-blind, placebocontrolled, phase IIIb trial (ATLAS) comparing bevacizumab (B) therapy with or without erlotinib (E) after completion of chemotherapy with B for first-line treatment of locally advanced, recurrent, or metastatic non-small cell lung cancer (NSCLC). J Clin Oncol, 27, 18s https://doi.org/10.1200/JCO.2009.22.4626
  17. Mok TS, Wu YL, Zhou C, et al (2009). Randomized, placebocontrolled, phase II study of sequential erlotinib and chemotherapy as first-line treatment for advanced non-smallcell lung cancer. J Clin Oncol, 27, 5080-7. https://doi.org/10.1200/JCO.2008.21.5541
  18. Novello S, Milella M, Tiseo M, et al (2011). Maintenance therapy in NSCLC: why? To whom? Which agent? J Exp Clin Cancer Res, 30, 50. https://doi.org/10.1186/1756-9966-30-50
  19. Ozkaya S, Findik S, Dirican A, Atici AG (2012). Long-term survival rates of patients with stage IIIB and IV non-small cell lung cancer treated with cisplatin plus vinorelbine or gemcitabine. Exp Ther Med, 4, 1035-8.
  20. Perol M, Arpin D (2011). Maintenance therapy in advanced non-small cell lung cancer: A new paradigm? Presse Med, 40, 404-14. https://doi.org/10.1016/j.lpm.2011.01.009
  21. Perol M, Chouaid C, Perol D, et al (2012). Randomized, phase III study of gemcitabine or erlotinib maintenance therapy versus observation, with predefined second-line treatment, after cisplatin-gemcitabine induction chemotherapy in advanced non-small-cell lung cancer. J Clin Oncol, 30, 3516-24. https://doi.org/10.1200/JCO.2011.39.9782
  22. Quan L, Chen W, Shu Y (2010). Current status and prospects of maintenance therapy in advanced stage non-small cell lung cancer. Chin J Lung Cancer, 13, 637-41.
  23. Reckamp KL (2012). Is benefit of maintenance therapy for NSCLC best defined by progression-free survival? Lancet Oncol, 13, 435-6. https://doi.org/10.1016/S1470-2045(12)70157-2
  24. Rinaldi M, Belvedere O, Cauchi C, et al (2006). Maintenance chemotherapy in non-small cell lung cancer. Ann Oncol, 17, 67-70.
  25. Takeda K, Hida T, Sato T, et al (2010). Randomized phase III trial of platinum-doublet chemotherapy followed by gefitinib compared with continued platinum-doublet chemotherapy in Japanese patients with advanced non-small-cell lung cancer: results of a west Japan thoracic oncology group trial (WJTOG0203). J Clin Oncol, 28, 753-60. https://doi.org/10.1200/JCO.2009.23.3445
  26. Velez M, Arango BA, Perez CA, Santos ES (2012). Safety and efficacy of pemetrexed in maintenance therapy of non-small cell lung cancer. Clin Med Insights Oncol, 6, 117-24 .
  27. Wu YL, Kim JH, Park K, et al (2012). Efficacy and safety of maintenance erlotinib in Asian patients with advanced non-small-cell lung cancer: a subanalysis of the phase III, randomized SATURN study. Lung cancer, 77, 339-45. https://doi.org/10.1016/j.lungcan.2012.03.012
  28. Xiao H, Ding J, Gao S, Yang S, Huang Y (2011). Never smokers with lung cancer: analysis of genetic variants. Asian Pac J Cancer Prev, 12, 2807-9.
  29. Yuan DM, Wei SZ, Lu YL, et al (2012). Single-agent maintenance therapy in non-small cell lung cancer: a systematic review and meta-analysis. Chin Med J (Engl), 125 , 3143-9.
  30. Zhang L, Ma S, Song X, et al (2012). Gefitinib versus placebo as maintenance therapy in patients with locally advanced or metastatic non-small-celllung cancer (INFOR M, C-TONG 0804): a multicentre, double-blind randomised phase 3 trial. Lancet Oncol, 13 ,466-75. https://doi.org/10.1016/S1470-2045(12)70117-1

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