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Efficacy and safety of cytotoxic drug chemotherapy after first-line EGFR–TKI treatment in elderly patients with non-small-cell lung cancer harboring sensitive EGFR mutations

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Abstract

Purpose

Epidermal growth factor receptor–tyrosine kinase inhibitor (EGFR–TKI) is effective as first-line chemotherapy for patients with advanced non-small-cell lung cancer (NSCLC) harboring sensitive EGFR mutations. However, whether the efficacy of second-line cytotoxic drug chemotherapy after first-line EGFR–TKI treatment is similar to that of first-line cytotoxic drug chemotherapy in elderly patients aged ≥ 75 years harboring sensitive EGFR mutations is unclear. Therefore, we aimed to investigate the efficacy and safety of cytotoxic drug chemotherapy after first-line EGFR–TKI treatment in elderly patients with NSCLC harboring sensitive EGFR mutations.

Methods

We retrospectively evaluated the clinical effects and safety profiles of second-line cytotoxic drug chemotherapy after first-line EGFR–TKI treatment in elderly patients with NSCLC harboring sensitive EGFR mutations (exon 19 deletion/exon 21 L858R mutation). Between April 2008 and December 2015, 78 elderly patients with advanced NSCLC harboring sensitive EGFR mutations received first-line EGFR–TKI at four Japanese institutions. Baseline characteristics, regimens, responses to first- and second-line treatments, whether or not patients received subsequent treatment, and if not, the reasons for non-administration were recorded.

Results

Overall, 20 patients with a median age of 79.5 years (range 75–85 years) were included in our analysis. The overall response, disease control, median progression-free survival, and overall survival rates were 15.0, 60.0%, 2.4, and 13.2 months, respectively. Common adverse events included leukopenia, neutropenia, anemia, thrombocytopenia, malaise, and anorexia. Major grade 3 or 4 toxicities included leukopenia (25.0%) and neutropenia (45.0%). No treatment-related deaths were noted.

Conclusion

Second-line cytotoxic drug chemotherapy after first-line EGFR–TKI treatment among elderly patients with NSCLC harboring sensitive EGFR mutations was effective and safe and showed equivalent outcomes to first-line cytotoxic drug chemotherapy.

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References

  1. Miller KD, Siegel RL, Lin CC et al (2016) Cancer treatment and survivorship statistics, 2016. CA Cancer J Clin 66:271–289

    Article  PubMed  Google Scholar 

  2. Davidoff AJ, Tang M, Seal B, Edelman MJ (2010) Chemotherapy and survival benefit in elderly patients with advanced non-small-cell lung cancer. J Clin Oncol 28:2191–2197

    Article  PubMed  Google Scholar 

  3. Owonikoko TK, Ragin CC, Belani CP, Oton AB, Gooding WE, Taioli E, Ramalingam SS (2007) Lung cancer in elderly patients: an analysis of the surveillance, epidemiology, and end results database. J Clin Oncol 25:5570–5577

    Article  PubMed  Google Scholar 

  4. Mok TS, Wu YL, Thongprasert S et al (2009) Gefitinib or carboplatin-paclitaxel in pulmonary adenocarcinoma. N Engl J Med 361:947–957

    Article  PubMed  CAS  Google Scholar 

  5. 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 362:2380–2388

    Article  PubMed  CAS  Google Scholar 

  6. 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 (WJTOG3405): an open label, randomised phase 3 trial. Lancet Oncol 11:121–128

    Article  PubMed  CAS  Google Scholar 

  7. Rosell R, Carcereney E, Gervais R et al (2012) 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 13:239–246

    Article  PubMed  CAS  Google Scholar 

  8. Zhou C, Wu YL, Chen G et al (2015) Final overall survival results from a randomised, phase III study of erlotinib versus chemotherapy as first-line treatment of EGFR mutation-positive advanced non-small-cell lung cancer (OPTIMAL, CTONG-0802). Ann Oncol 26:1877–1883

    Article  PubMed  CAS  Google Scholar 

  9. 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 16:141–151

    Article  PubMed  CAS  Google Scholar 

  10. Maemondo M, Minegishi Y, Inoue A et al (2012) First-line gefitinib in patients aged 75 or older with advanced non-small cell lung cancer harboring epidermal growth factor receptor mutations: NEJ 003 study. J Thorac Oncol 7:1417–1422

    Article  PubMed  CAS  Google Scholar 

  11. Fujita S, Katakami N, Masago K et al (2012) Customized chemotherapy based on epidermal growth factor receptor mutation status for elderly patients with advanced non-small-cell lung cancer: a phase II trial. BMC Cancer 12:185

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  12. Tateishi K, Ichiyama T, Hirai K et al (2013) Clinical outcomes in elderly patients administered gefitinib as first-line treatment in epidermal growth factor receptor-mutated non-small-cell lung cancer: retrospective analysis in a Nagano Lung Cancer Research Group study. Med Oncol 30:450

    Article  PubMed  CAS  Google Scholar 

  13. Goto K, Nishio M, Yamamoto N et al (2013) A prospective, phase II, open-label study (JO22903) of first-line erlotinib in Japanese patients with epidermal growth factor receptor (EGFR) mutation-positive advanced non-small-cell lung cancer (NSCLC). Lung Cancer 82:109–114

    Article  PubMed  Google Scholar 

  14. Takahashi K, Saito H, Hashegawa Y et al (2014) First-line gefitinib therapy for elderly patients with non-small cell lung cancer harboring EGFR mutation: Central Japan Lung Study Group 0901. Cancer Chemother Pharmacol 74:721–727

    Article  PubMed  CAS  Google Scholar 

  15. Kuwako T, Imai H, Masuda T et al (2015) First-line gefitinib treatment in elderly patients (aged>/=75 years) with non-small cell lung cancer harboring EGFR mutations. Cancer Chemother Pharmacol 76:761–769

    Article  PubMed  CAS  Google Scholar 

  16. Yoshino R, Imai H, Mori K et al (2014) Surrogate endpoints for overall survival in advanced non-small-cell lung cancer patients with mutations of the epidermal growth factor receptor gene. Mol Clin Oncol 2:731–736

    Article  PubMed  PubMed Central  Google Scholar 

  17. 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 chemo-naive non-small cell lung cancer with sensitive EGFR gene mutations (NEJ002). Ann Oncol 24:54–59

    Article  PubMed  CAS  Google Scholar 

  18. Kobayashi S, Boggon TJ, Dayaram T et al (2005) EGFR mutation and resistance of non-small-cell lung cancer to gefitinib. N Engl J Med 352:786–792

    Article  PubMed  CAS  Google Scholar 

  19. Sequist LV, Waltman BA, Dias-Santagata D et al (2011) Genotypic and histological evolution of lung cancers acquiring resistance to EGFR inhibitors. Sci Transl Med 3:75ra26

    Article  PubMed  PubMed Central  Google Scholar 

  20. Oxnard GR, Arcila ME, Sima CS et al (2011) Acquired resistance to EGFR tyrosine kinase inhibitors in EGFR-mutant lung cancer: distinct natural history of patients with tumors harboring the T790M mutation. Clin Cancer Res 17:1616–1622

    Article  PubMed  CAS  Google Scholar 

  21. Yu HA, Arcila ME, Rekhtman N et al (2013) Analysis of tumor specimens at the time of acquired resistance to EGFR-TKI therapy in 155 patients with EGFR-mutant lung cancers. Clin Cancer Res 19:2240–2247

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  22. Oxnard GR, Arcila ME, Chmielecki J, Ladanyi M, Miller VA, Pao W (2011) New strategies in overcoming acquired resistance to epidermal growth factor receptor tyrosine kinase inhibitors in lung cancer. Clin Cancer Res 17:5530–5537

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  23. Gridelli C, Shepherd FA (2005) Chemotherapy for elderly patients with non-small cell lung cancer: a review of the evidence. Chest 128:947–957

    Article  PubMed  Google Scholar 

  24. Belani CP, Fossella F (2005) Elderly subgroup analysis of a randomized phase III study of docetaxel plus platinum combinations versus vinorelbine plus cisplatin for first-line treatment of advanced nonsmall cell lung carcinoma (TAX 326). Cancer 104:2766–2774

    Article  PubMed  CAS  Google Scholar 

  25. Novello S, Barlesi F, Califano R et al (2016) Metastatic non-small-cell lung cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 27:v1-v27

    Article  PubMed  Google Scholar 

  26. No authors listed (1999) Effects of vinorelbine on quality of life and survival of elderly patients with advanced non-small-cell lung cancer. The Elderly Lung Cancer Vinorelbine Italian Study Group. J Natl Cancer Inst 91:66–72

    Article  Google Scholar 

  27. Gridelli C, Perrone F, Gallo C et al (2003) Chemotherapy for elderly patients with advanced non-small-cell lung cancer: the Multicenter Italian Lung Cancer in the Elderly Study (MILES) phase III randomized trial. J Natl Cancer Inst 95:362–372

    Article  PubMed  CAS  Google Scholar 

  28. Kudoh S, Takeda K, Nakagawa K et al (2006) Phase III study of docetaxel compared with vinorelbine in elderly patients with advanced non-small-cell lung cancer: results of the West Japan Thoracic Oncology Group Trial (WJTOG 9904). J Clin Oncol 24:3657–3663

    Article  PubMed  CAS  Google Scholar 

  29. Goldstraw P, Crowley J, Chansky K et al (2007) The IASLC Lung Cancer Staging Project: proposals for the revision of the TNM stage groupings in the forthcoming (seventh) edition of the TNM Classification of malignant tumours. J Thorac Oncol 2:706–714

    Article  PubMed  Google Scholar 

  30. Nagai Y, Miyazawa H, Hugun et al (2005) Genetic heterogeneity of the epidermal growth factor receptor in non-small cell lung cancer cell lines revealed by a rapid and sensitive detection system, the peptide nucleic acid-locked nucleic acid PCR clamp. Cancer Res 65:7276–7282

    Article  PubMed  CAS  Google Scholar 

  31. Yatabe Y, Hida T, Horio Y, Kosaka T, Takahashi T, Mitsudomi T (2006) A rapid, sensitive assay to detect EGFR mutation in small biopsy specimens from lung cancer. J Mol Diagn 8:335–341

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  32. Eisenhauer EA, Therasse P, Bogaerts J et al (2009) New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer 45:228–247

    Article  PubMed  CAS  Google Scholar 

  33. Abe T, Takeda K, Ohe Y et al (2015) Randomized phase III trial comparing weekly docetaxel plus cisplatin versus docetaxel monotherapy every 3 weeks in elderly patients with advanced non-small-cell lung cancer: the intergroup trial JCOG0803/WJOG4307L. J Clin Oncol 33:575–581

    Article  PubMed  CAS  Google Scholar 

  34. Takeuchi S, Yano S (2014) Clinical significance of epidermal growth factor receptor tyrosine kinase inhibitors: sensitivity and resistance. Respir Investig 52:348–356

    Article  PubMed  Google Scholar 

  35. Mok TS, Wu YL, Ahn MJ et al (2017) Osimertinib or platinum-pemetrexed in EGFR T790M-positive lung cancer. N Engl J Med 376:629–640

    Article  PubMed  CAS  Google Scholar 

  36. Soria JC, Wu YL, Nakagawa Y et al (2015) Gefitinib plus chemotherapy versus placebo plus chemotherapy in EGFR-mutation-positive non-small-cell lung cancer after progression on first-line gefitinib (IMPRESS): a phase 3 randomised trial. Lancet Oncol 16:990–998

    Article  PubMed  CAS  Google Scholar 

  37. Quoix E, Zalcman G, Oster JP et al (2011) Carboplatin and weekly paclitaxel doublet chemotherapy compared with monotherapy in elderly patients with advanced non-small-cell lung cancer: IFCT-0501 randomised, phase 3 trial. Lancet 378:1079–1088

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgements

We thank Drs. Tomohiro Tamura, Sakae Fujimoto, Hiroshi Yokouchi, Yoichi Nakamura, and Takeshi Hisada for their assistance in preparing this manuscript. We also thank Editage (http://www.editage.jp) for English language editing.

Author information

Authors and Affiliations

  1. Division of Respiratory Medicine, Gunma Prefectural Cancer Center, 617-1, Takahayashinishi, Ota, Gunma, 373-8550, Japan

    Hisao Imai & Koichi Minato

  2. Department of Pulmonary Medicine, Fukushima Medical University, Fukushima, Japan

    Hiroyuki Minemura & Kenya Kanazawa

  3. Division of Thoracic Oncology, Tochigi Cancer Center, Utsunomiya, Tochigi, Japan

    Tomohide Sugiyama & Takashi Kasai

  4. Division of Respiratory Medicine, Ibaraki Prefectural Central Hospital, Kasama, Ibaraki, Japan

    Yutaka Yamada & Takayuki Kaburagi

  5. Department of Oncology Clinical Development, Gunma University Graduate School of Medicine, Maebashi, Gunma, Japan

    Kyoichi Kaira

  6. Clinical Oncology Center, Fukushima Medical University Hospital, Fukushima, Japan

    Kenya Kanazawa

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  1. Hisao Imai
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Gunma-Ibaraki-Fukushima-Tochigi (GIFT) Group

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Correspondence to Hisao Imai.

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None of the authors have any financial or personal relationships with people or organizations that could inappropriately influence this work.

Ethical approval

The institutional review board of each institution approved the study protocol.

Informed consent

The need for informed consent was waived by the Institutional Review Boards of each participating institution because of the retrospective nature of the study.

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Imai, H., Minemura, H., Sugiyama, T. et al. Efficacy and safety of cytotoxic drug chemotherapy after first-line EGFR–TKI treatment in elderly patients with non-small-cell lung cancer harboring sensitive EGFR mutations. Cancer Chemother Pharmacol 82, 119–127 (2018). https://doi.org/10.1007/s00280-018-3596-6

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  • DOI: https://doi.org/10.1007/s00280-018-3596-6

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