DOI QR코드

DOI QR Code

EGFR Mutation Genotype Impact on the Efficacy of Pemetrexed in Patients with Non-squamous Non-small Cell Lung Cancer

  • Igawa, Satoshi (Department of Respiratory Medicine, Kitasato University School of Medicine) ;
  • Sato, Yuichi (School of Allied Health Sciences, School of Medicine, Kitasato University) ;
  • Ishihara, Mikiko (Department of Respiratory Medicine, Kitasato University School of Medicine) ;
  • Kasajima, Masashi (Department of Respiratory Medicine, Kitasato University School of Medicine) ;
  • Kusuhara, Seiichiro (Department of Respiratory Medicine, Kitasato University School of Medicine) ;
  • Nakahara, Yoshiro (Department of Respiratory Medicine, Kitasato University School of Medicine) ;
  • Otani, Sakiko (Department of Respiratory Medicine, Kitasato University School of Medicine) ;
  • Fukui, Tomoya (Department of Respiratory Medicine, Kitasato University School of Medicine) ;
  • Katagiri, Masato (School of Allied Health Sciences, School of Medicine, Kitasato University) ;
  • Sasaki, Jiichiro (Research and Development Center for New Medical Frontiers, School of Medicine, Kitasato University) ;
  • Masuda, Noriyuki (Department of Respiratory Medicine, Kitasato University School of Medicine)
  • Published : 2016.07.01

Abstract

Background: Pemetrexed monotherapy has come to be recognized as one of the standard second-line therapies for advanced non-squamous non-small cell lung cancer (NSCLC). However, there have been no reports of studies that have evaluated the efficacy of pemetrexed according to type of active EGFR mutation, i.e., an exon 19 deletion or an L858R point mutation. Materials and Methods: The records of non-squamous NSCLC patients harboring an EGFR mutation who received pemetrexed monotherapy as a second or later line of chemotherapy at Kitasato University Hospital between March 2010 and October 2015 were retrospectively reviewed, and the treatment outcomes were evaluated. Results: The overall response rate and progression-free survival time (PFS) of the 53 patients with non-squamous NSCLC were 15.1% and 2.3 months, respectively. There were significant differences between the disease control rate (37.5% vs. 76.2%) and PFS time (1.8 months vs. 3.3 months) of the exon 19 deletion group and the L858R point mutation group, and a multivariate analysis identified type of EGFR mutation as well as performance status (PS) as independent predictors of PFS. Conclusions: The clinical data obtained in this study provided a valuable rationale for considering type of EGFR mutation as well as non-squamous histology as predictors of the efficacy of pemetrexed monotherapy.

Keywords

Non-squamous non-small cell lung cancer;Pemetrexed;Predictor;EGFR mutation

References

  1. Alharbi KK (2015). Clinical efficacy and possible applications of genomics in lung cancer. Asian Pac J Cancer Prev, 16, 1693-8. https://doi.org/10.7314/APJCP.2015.16.5.1693
  2. Carey KD, Garton AJ, Romero MS, et al (2006). Kinetic analysis of epidermal growth factor receptor somatic mutant proteins shows increased sensitivity to the epidermal growth factor receptor tyrosine kinase inhibitor, erlotinib. Cancer Res, 66, 8163-71. https://doi.org/10.1158/0008-5472.CAN-06-0453
  3. Ciuleanu T, Brodowicz T, Zielinski C, et al (2009). Maintenance pemetrexed plus best supportive care versus placebo plus best sup- portive care for non-small-cell lung cancer:a randomized,double-blind,phase 3 study. Lancet, 374, 1432-40. https://doi.org/10.1016/S0140-6736(09)61497-5
  4. Di BS, Wei KP, Tian JH, et al (2014). Effectiveness and safety of pemetrexed versus docetaxel as a treatment for advanced small cell lung cancer: a systematic review and metaanalysis. Asian Pac J Cancer Prev, 15, 3419-24. https://doi.org/10.7314/APJCP.2014.15.8.3419
  5. Fukihara J, Watanabe N, Taniguchi H, et al (2014). Clinical predictors of response to egfr tyrosine kinase inhibitors in patients with egfr-mutant non-small cell lung cancer. Oncol, 86, 86-93. https://doi.org/10.1159/000357129
  6. Giovannetti E, Lemos C, Tekle C, et al (2008). Molecular mechanisms underlying the synergistic interaction of erlotinib, an epidermal growth factor receptor tyrosine kinase inhibitor, with the multitargeted antifolate pemetrexed in non-small-cell lung cancer cells. Mol Pharmacol, 73, 1290-300. https://doi.org/10.1124/mol.107.042382
  7. Hanna N, Shepherd FA, Fossella FV (2004). Randomized phase III trial of pemetrexed versus docetaxel in patients with nonsmall-cell lung cancer previously treated with chemotherapy. J Clin Oncol, 22, 1589-97. https://doi.org/10.1200/JCO.2004.08.163
  8. Hasegawa Y, Ando M, Maemondo M, et al (2015). The role of smoking status on the progression-free survival of non-small cell lung cancer patients harboring activating epidermal growth factor receptor (EGFR) mutations receiving first-line EGFR tyrosine kinase inhibitor versus platinum doublet chemotherapy: a meta-analysis of prospective randomized trials. The Oncologist, 20, 307-15. https://doi.org/10.1634/theoncologist.2014-0285
  9. Huang XE, Tian GY, Cao J, et al (2014). Pemetrexed as a component of first-, second- and third- line chemotherapy in treating patients with metastatic lung adenocarcinoma. Asian Pac J Cancer Prev, 14, 6663-7.
  10. Inoue A, Kobayashi K, Maemondo M, et al (2013). Updated overall survival results from a randomized phase III trial comparing gefitinib with carboplatin-paclitaxel for chemonaive non-small cell lung cancer with sensitive EGFR gene mutations (NEJ002). Ann Oncol, 24, 54-9. https://doi.org/10.1093/annonc/mds214
  11. Jiang X, Yang B, Lu J, et al (2015). Pemetrexed-based chemotherapy in advanced lung adenocarcinoma patients with different EGFRgenotypes. Tumour Biol, 36, 861-9. https://doi.org/10.1007/s13277-014-2692-4
  12. Joerger M, Omlin A, Cerny T, et al (2010). The role of pemetrexed in advanced non small-cell lung cancer: special focus on pharmacology and mechanism of action. Curr Drug Targets, 11, 37-47. https://doi.org/10.2174/138945010790030974
  13. Kubota K, Niho S, Enatsu S, et al (2009). Efficacy differences of pemetrexed by histology in pretreated patients with stage IIIB/IV non-small cell lung cancer: review of results from an open-label randomized phase II study. J Thorac Oncol, 4, 1530-6. https://doi.org/10.1097/JTO.0b013e3181b9e608
  14. Lee CK, Wu YL, Ding PN, et al (2015). Impact of specific epidermal growth factor receptor (EGFR) mutations and clinical characteristics on outcomes after treatment with EGFR tyrosine kinase inhibitors versus chemotherapy in EGFR-mutant lung cancer: a meta-analysis. J Clin Oncol, 33, 1958-65. https://doi.org/10.1200/JCO.2014.58.1736
  15. Liu Q, Yu Z, Xiang Y, et al (2015). Prognostic and predictive significance of thymidylate synthase protein expression in non-small cell lung cancer: a systematic review and metaanalysis. Cancer Biomark, 15, 65-78. https://doi.org/10.3233/CBM-140432
  16. Liu Y, Yin TJ, Zhou R, et al (2013). Expression of thymidylate synthase predicts clinical outcomes of pemetrexedcontainingchemotherapy for non-small-cell lung cancer: a systemic review and meta-analysis. Cancer Chemother Pharmacol, 72, 1125-32. https://doi.org/10.1007/s00280-013-2299-2
  17. Lynch TJ, Bell DW, Sordella R, et al (2004). Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small-cell lung cancer to gefitinib. N Engl J Med, 350, 2129-39. https://doi.org/10.1056/NEJMoa040938
  18. Maemondo M, Inoue A, Kobayashi K, et al (2010). Gefitinib or chemotherapy for non-small-cell lung cancer with mutated egfr. N Engl J Med, 362, 2380-8. https://doi.org/10.1056/NEJMoa0909530
  19. Matam K, Goud I, Lakshmi M, et al (2015). Correlation between EGFR Gene Mutations and Lung Cancer: a Hospital-Based Study. Asian Pac J Cancer Prev, 16, 7071-6. https://doi.org/10.7314/APJCP.2015.16.16.7071
  20. Mitsudomi T, Kosaka T, Yatabe Y, (2006). Biological and clinical implications of EGFR mutations in lung cancer. Int J Clin Oncol, 11, 190-8. https://doi.org/10.1007/s10147-006-0583-4
  21. Mitsudomi T, Morita S, Yatabe Y, et al (2010). Gefitinib versus cisplatin plus docetaxel in patients with non-small-cell lung cancer harbouring mutations of the epidermal growth factor receptor (WJTOG 3405): An open label, randomised phase 3 trial. Lancet Oncol, 11, 121-8. https://doi.org/10.1016/S1470-2045(09)70364-X
  22. Nakamura R, Inage Y, Tobita R, et al (2014). Epidermal growth factor receptor mutations: effect on volume doubling time of non-small-cell lung cancer patients. J Thorac Oncol, 9, 1340-4. https://doi.org/10.1097/JTO.0000000000000022
  23. Ohe Y, Ichinose Y, Nakagawa K, et al (2008). Efficacy and safety of two doses of pemetrexed supplemented with folic acid and vitamin B12 in previously treated patients with non-small cell lung cancer. Clin Cancer Res, 14, 4206-12. https://doi.org/10.1158/1078-0432.CCR-07-5143
  24. Ohe Y, Ohashi Y, Kubota K, et al (2007). Randomized phase III study of cisplatin plus irinotecan versus carboplatin plus paclitaxel, cisplatin plus gemcitabine, and cisplatin plus vinorelbine for advanced non-small-cell lung cancer: Four-Arm Cooperative Study in Japan. Ann Oncol, 18, 317-23.
  25. Okami J, Taniguchi K, Higashiyama M, et al (2007). Prognostic factors for gefitinib-treated postoperative recurrence in nonsmall cell lung cancer. Oncol, 72, 234-42. https://doi.org/10.1159/000112947
  26. Paez JG, Janne PA, Lee JC, et al (2004). EGFR mutations in lung cancer: correlation with clinical response to gefitinib therapy. Sci, 304, 1497-500. https://doi.org/10.1126/science.1099314
  27. Pao W, Miller V, Zakowski M, et al (2004). EGF receptor gene mutations are common in lung cancers from "never smokers" and are associated with sensitivity of tumors to gefitinib and erlotinib. Proc Natl Acad Sci U S A, 101, 13306-11. https://doi.org/10.1073/pnas.0405220101
  28. Rossi A, Galetta D, Gridelli C (2014). Biological prognostic and predictive factors in lung cancer. Oncol, 77, 90-6.
  29. Schiller JH (2001). Current standards of care in small-cell and non-small-cell lung cancer. Oncol, 61, 3-13. https://doi.org/10.1159/000055386
  30. Schiller JH, Harrington D, Belani CP, et al (2002). Comparison of four chemotherapy regimens for advanced non-small-cell lung cancer. N Engl J Med, 346, 92-8. https://doi.org/10.1056/NEJMoa011954
  31. Solomon B, Bunn Jr PA (2005). Clinical activity of pemetrexed: a multitargeted antifolateanticancer agent. Future Oncol, 1, 733-46. https://doi.org/10.2217/14796694.1.6.733
  32. Wang L, Wang R, Pan Y, et al (2014). The pemetrexedcontaining treatments in the non-small cell lung cancer, is -/low thymidylate synthase expression better than +/high thymidylate synthase expression: a meta-analysis. BMC Cancer, 14, 205. https://doi.org/10.1186/1471-2407-14-205
  33. Wang T, Chuan PC, Rui YJ, et al (2013). Association between TYMS Expression and Efficacy of Pemetrexed-Based Chemotherapy in Advanced Non-Small Cell Lung Cancer: A Meta-Analysis. PLoS One, 8, 74284. https://doi.org/10.1371/journal.pone.0074284
  34. Wu SG, Yang CH, Yu CJ, et al (2011). Good response to pemetrexed in patients of lung adenocarcinoma with epidermal growth factor receptor (EGFR) mutations. Lung Cancer, 72, 333-9. https://doi.org/10.1016/j.lungcan.2010.10.012
  35. Yang JC, Wu YL, Schuler M, et al (2015). Afatinib versus cisplatin-based chemotherapy for egfr mutation-positive lung adenocarcinoma (lux-lung 3 and lux-lung 6): Analysis of overall survival data from two randomised, phase 3 trials. Lancet Oncol, 16, 141-51. https://doi.org/10.1016/S1470-2045(14)71173-8