DOI QR코드

DOI QR Code

Pemetrexed Continuation Maintenance versus Conventional Platinum-Based Doublet Chemotherapy in EGFR-Negative Lung Adenocarcinoma: Retrospective Analysis

  • Paik, Seung Sook (Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Dongnam Institute of Radiological & Medical Sciences) ;
  • Hwang, In Kyoung (Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Dongnam Institute of Radiological & Medical Sciences) ;
  • Park, Myung Jae (Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Kyung Hee University School of Medicine) ;
  • Lee, Seung Hyeun (Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Kyung Hee University School of Medicine)
  • Received : 2017.08.01
  • Accepted : 2017.10.02
  • Published : 2018.04.30

Abstract

Background: Although targeted therapy and immuno-oncology have shifted the treatment paradigm for lung cancer, platinum-based combination is still the standard of care for advanced non-small cell lung cancer (NSCLC). Pemetrexed continuation maintenance therapy has been approved and increasingly used for patients with nonsquamous NSCLC. However, the efficacy of this strategy has not been proven in patients without driving mutations. The objective of this study was to compare the clinical benefit of pemetrexed continuation maintenance to conventional platinum-based doublet in epidermal growth factor receptor (EGFR)-negative lung adenocarcinoma. Methods: A total of 114 patients with EGFR-negative lung adenocarcinoma who were treated with platinum doublet were retrospectively enrolled. We compared the survival rates between patients received pemetrexed maintenance after four-cycled pemetrexed/cisplatin and those received at least four-cycled platinum doublet without maintenance chemotherapy as a first-line treatment. Results: Forty-one patients received pemetrexed maintenance and 73 received conventional platinum doublet. Median progression-free survival (PFS), which was defined as the time from the day of response evaluation after four cycles of chemotherapy to disease progression or death, was significantly higher in the pemetrexed maintenance group compared to conventional group (5.8 months vs. 2.2 months, p<0.001). Median overall survival showed an increasing trend in the pemetrexed maintenance group (22.3 months vs. 16.1 months, p=0.098). Multivariate analyses showed that pemetrexed maintenance chemotherapy was associated with better PFS (hazard ratio, 0.73; 95% confidence interval, 0.15-0.87). Conclusion: Compared to conventional platinum-based chemotherapy, premetrexed continuation maintenance treatment is associated with better clinical outcome for the patients with EGFR wild-type lung adenocarcinoma.

Acknowledgement

Supported by : National Research Foundation of Korea (NRF)

References

  1. Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J, Jemal A. Global cancer statistics, 2012. CA Cancer J Clin 2015;65:87-108. https://doi.org/10.3322/caac.21262
  2. Park JY, Jang SH. Epidemiology of Lung Cancer in Korea: Recent Trends. Tuberc Respir Dis (Seoul) 2016;79:58-69.
  3. Bansal P, Osman D, Gan GN, Simon GR, Boumber Y. Recent advances in targetable therapeutics in metastatic non-squamous NSCLC. Front Oncol 2016;6:112.
  4. Reck M, Rodriguez-Abreu D, Robinson AG, Hui R, Csoszi T, Fulop A, et al. Pembrolizumab versus chemotherapy for PD-L1-positive non-small-cell lung cancer. N Engl J Med 2016;375:1823-33. https://doi.org/10.1056/NEJMoa1606774
  5. Peters S, Gettinger S, Johnson ML, Janne PA, Garassino MC, Christoph D, et al. Phase II trial of atezolizumab as first-line or subsequent therapy for patients with programmed deathligand 1-selected advanced non-small-cell lung cancer (BIRCH). J Clin Oncol 2017;35:2781-9. https://doi.org/10.1200/JCO.2016.71.9476
  6. Borghaei H, Paz-Ares L, Horn L, Spigel DR, Steins M, Ready NE, et al. Nivolumab versus docetaxel in advanced nonsquamous non-small-cell lung cancer. N Engl J Med 2015;373:1627-39. https://doi.org/10.1056/NEJMoa1507643
  7. Chang YS, Choi CM, Lee JC. Mechanisms of Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor Resistance and Strategies to Overcome Resistance in Lung Adenocarcinoma. Tuberc Respir Dis (Seoul) 2016;79:248-56. https://doi.org/10.4046/trd.2016.79.4.248
  8. National Comprehensive Cancer Network guidelines [Internet]. Fort Washington: National Comprehensive Cancer Network; 2017 [cited 2017 Jul 15]. Available from: http://www.nccn.org/professionals/physician_gls/pdf/nscl.pdf.
  9. Masters GA, Temin S, Azzoli CG, Giaccone G, Baker S Jr, Brahmer JR, et al. Systemic therapy for stage IV non-small-cell lung cancer: American Society of Clinical Oncology clinical practice guideline update. J Clin Oncol 2015;33:3488-515. https://doi.org/10.1200/JCO.2015.62.1342
  10. Joerger M, Omlin A, Cerny T, Fruh M. The role of pemetrexed in advanced non small-cell lung cancer: special focus on pharmacology and mechanism of action. Curr Drug Targets 2010;11:37-47. https://doi.org/10.2174/138945010790030974
  11. Scagliotti GV, Parikh P, von Pawel J, Biesma B, Vansteenkiste J, Manegold C, et al. Phase III study comparing cisplatin plus gemcitabine with cisplatin plus pemetrexed in chemotherapy-naive patients with advanced-stage non-small-cell lung cancer. J Clin Oncol 2008;26:3543-51. https://doi.org/10.1200/JCO.2007.15.0375
  12. Wu YL, Lu S, Cheng Y, Zhou C, Wang M, Qin S, et al. Efficacy and safety of pemetrexed/cisplatin versus gemcitabine/cisplatin as first-line treatment in Chinese patients with advanced nonsquamous non-small cell lung cancer. Lung Cancer 2014;85:401-7. https://doi.org/10.1016/j.lungcan.2014.07.007
  13. Yang CH, Simms L, Park K, Lee JS, Scagliotti G, Orlando M. Efficacy and safety of cisplatin/pemetrexed versus cisplatin/ gemcitabine as first-line treatment in East Asian patients with advanced non-small cell lung cancer: results of an exploratory subgroup analysis of a phase III trial. J Thorac Oncol 2010;5:688-95. https://doi.org/10.1097/JTO.0b013e3181d1273d
  14. Belani CP, Brodowicz T, Ciuleanu TE, Krzakowski M, Yang SH, Franke F, et al. Quality of life in patients with advanced non-small-cell lung cancer given maintenance treatment with pemetrexed versus placebo (H3E-MC-JMEN): results from a randomised, double-blind, phase 3 study. Lancet Oncol 2012;13:292-9. https://doi.org/10.1016/S1470-2045(11)70339-4
  15. Paz-Ares LG, de Marinis F, Dediu M, Thomas M, Pujol JL, Bidoli P, et al. PARAMOUNT: Final overall survival results of the phase III study of maintenance pemetrexed versus placebo immediately after induction treatment with pemetrexed plus cisplatin for advanced nonsquamous non-small-cell lung cancer. J Clin Oncol 2013;31:2895-902. https://doi.org/10.1200/JCO.2012.47.1102
  16. Belani CP, Wu YL, Chen YM, Kim JH, Yang SH, Zhang L, et al. Efficacy and safety of pemetrexed maintenance therapy versus best supportive care in patients from East Asia with advanced, nonsquamous non-small cell lung cancer: an exploratory subgroup analysis of a global, randomized, phase 3 clinical trial. J Thorac Oncol 2012;7:567-73. https://doi.org/10.1097/JTO.0b013e31823d4f9d
  17. Park S, Kim HJ, Choi CM, Lee DH, Kim SW, Lee JS, et al. Predictive factors for a long-term response duration in nonsquamous cell lung cancer patients treated with pemetrexed. BMC Cancer 2016;16:417. https://doi.org/10.1186/s12885-016-2457-0
  18. Park S, Park TS, Choi CM, Lee DH, Kim SW, Lee JS, et al. Survival benefit of pemetrexed in lung adenocarcinoma patients with anaplastic lymphoma kinase gene rearrangements. Clin Lung Cancer 2015;16:e83-9. https://doi.org/10.1016/j.cllc.2015.01.003
  19. Goldstraw P. The 7th edition of TNM in lung cancer: what now? J Thorac Oncol 2009;4:671-3.
  20. Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, et al. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer 2009;45:228-47. https://doi.org/10.1016/j.ejca.2008.10.026
  21. Hwang KE, Kim HR. Response Evaluation of Chemotherapy for Lung Cancer. Tuberc Respir Dis (Seoul) 2017;80:136-42. https://doi.org/10.4046/trd.2017.80.2.136
  22. Gerber DE, Rasco DW, Le P, Yan J, Dowell JE, Xie Y. Predictors and impact of second-line chemotherapy for advanced nonsmall cell lung cancer in the United States: real-world considerations for maintenance therapy. J Thorac Oncol 2011;6:365-71. https://doi.org/10.1097/JTO.0b013e3181fff142
  23. Ciuleanu T, Brodowicz T, Zielinski C, Kim JH, Krzakowski M, Laack E, et al. Maintenance pemetrexed plus best supportive care versus placebo plus best supportive care for non-smallcell lung cancer: a randomised, double-blind, phase 3 study. Lancet 2009;374:1432-40. https://doi.org/10.1016/S0140-6736(09)61497-5
  24. Cappuzzo F, Ciuleanu T, Stelmakh L, Cicenas S, Szczesna A, Juhasz E, et al. Erlotinib as maintenance treatment in advanced non-small-cell lung cancer: a multicentre, randomised, placebo-controlled phase 3 study. Lancet Oncol 2010;11:521-9. https://doi.org/10.1016/S1470-2045(10)70112-1
  25. Mubarak N, Gaafar R, Shehata S, Hashem T, Abigeres D, Azim HA, et al. A randomized, phase 2 study comparing pemetrexed plus best supportive care versus best supportive care as maintenance therapy after first-line treatment with pemetrexed and cisplatin for advanced, non-squamous, non-small cell lung cancer. BMC Cancer 2012;12:423. https://doi.org/10.1186/1471-2407-12-423
  26. Paz-Ares L, de Marinis F, Dediu M, Thomas M, Pujol JL, Bidoli P, et al. Maintenance therapy with pemetrexed plus best supportive care versus placebo plus best supportive care after induction therapy with pemetrexed plus cisplatin for advanced non-squamous non-small-cell lung cancer (PARAMOUNT): a double-blind, phase 3, randomised controlled trial. Lancet Oncol 2012;13:247-55.
  27. Jiang X, Yang B, Lu J, Zhan Z, Li K, Ren X. Pemetrexed-based chemotherapy in advanced lung adenocarcinoma patients with different EGFR genotypes. Tumour Biol 2015;36:861-9.
  28. Hanna N, Shepherd FA, Fossella FV, Pereira JR, De Marinis F, von Pawel J, 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 2004;22:1589-97. https://doi.org/10.1200/JCO.2004.08.163
  29. Yoh K, Goto Y, Naito Y, Kishi K, Mori K, Hotta K, et al. Impact of maintenance therapy for patients with non-small cell lung cancer in a real-world setting. Anticancer Res 2017;37:1507-13. https://doi.org/10.21873/anticanres.11478
  30. Lee JK, Hahn S, Kim DW, Suh KJ, Keam B, Kim TM, et al. Epidermal growth factor receptor tyrosine kinase inhibitors vs conventional chemotherapy in non-small cell lung cancer harboring wild-type epidermal growth factor receptor: a meta-analysis. JAMA 2014;311:1430-7. https://doi.org/10.1001/jama.2014.3314
  31. Lee JO, Kim TM, Lee SH, Kim DW, Kim S, Jeon YK, et al. Anaplastic lymphoma kinase translocation: a predictive biomarker of pemetrexed in patients with non-small cell lung cancer. J Thorac Oncol 2011;6:1474-80. https://doi.org/10.1097/JTO.0b013e3182208fc2