EGFR Tyrosine Kinase Inhibitors Prolong Overall Survival in EGFR Mutated Non-Small-Cell Lung Cancer Patients with Postsurgical Recurrence

Authors

  • Kenichi Suda Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka
  • Simon Ito Departments of Thoracic Surgery, Aichi Cancer Center Hospital, 1-1 Kanokoden, Chikusa-ku, Nagoya
  • Hiroshi Mizuuchi Departments of Thoracic Surgery, Aichi Cancer Center Hospital, 1-1 Kanokoden, Chikusa-ku, Nagoya
  • Yoshihiko Maehara Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka
  • Yasushi Yatabe Pathology and Molecular Diagnostics, Aichi Cancer Center Hospital, 1-1 Kanokoden, Chikusa-ku, Nagoya
  • Tetsuya Mitsudomi Division of Thoracic Surgery, Department of Surgery, Kinki University Faculty of Medicine, 377-2 Ohno-Higashi, Osaka-Sayama, Japan

DOI:

https://doi.org/10.6000/1929-2279.2012.01.01.15

Keywords:

Molecular target therapy, biomarker analysis, prognostic factor, predictive factor, gefitinib, erlotinib, pulmonary resection, postsurgical recurrence-free survival (RFS), postrecurrence survival (PRS).

Abstract

 It is indisputable that epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) prolong progression-free survival in non-small-cell lung cancer (NSCLC) patients with EGFR mutations better than cytotoxic chemotherapy. However, it is unclear whether EGFR-TKIs prolong the overall survival of NSCLC patients, especially in those with postsurgical recurrence.We retrospectively examined 304 NSCLC patients with known EGFR mutational status (excluding those with squamous cell carcinoma), who had undergone pulmonary resection and experienced postsurgical recurrence. Of these patients, 137 carried EGFR mutations and 167 did not. Of the 137 patients with EGFR mutations, 83 were treated with EGFR-TKIs for their recurrent disease, and 32 of the 167 patients without EGFR mutations were treated with EGFR-TKIs. Postsurgical survival was divided into two parts: recurrence-free survival (RFS) and postrecurrence survival (PRS), and these were compared between the subgroups with a multivariate analysis, adjusted for baseline clinical characteristics.There was no significant difference in RFS between patients with EGFR mutations and those without (P = 0.88). PRS was also similar in these two subgroups when we excluded patients who had been treated with EGFR-TKIs (P = 0.64). In patients with EGFR mutations, PRS was significantly longer in those who were treated with EGFR-TKIs than in those who were not given EGFR-TKIs (P = 0.04). However, among patients without EGFR mutations, PRS was similar in patients who had and had not been treated with EGFR-TKIs (P = 0.87). In conclusion, among NSCLC patients with postsurgical recurrence, EGFR-TKIs prolonged PRS in those with EGFR mutations.

References

Lynch TJ, Bell DW, Sordella R, et al. Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small-cell lung cancer to gefitinib. N Engl J Med 2004; 350: 2129-39. http://dx.doi.org/10.1056/NEJMoa040938

Paez JG, Janne PA, Lee JC, et al. EGFR mutations in lung cancer: correlation with clinical response to gefitinib therapy. Science 2004; 304: 1497-500. http://dx.doi.org/10.1126/science.1099314

Mitsudomi T, Kosaka T, Endoh H, et al. Mutations of the epidermal growth factor receptor gene predict prolonged survival after gefitinib treatment in patients with non-small-cell lung cancer with postoperative recurrence. J Clin Oncol 2005; 23: 2513-20. http://dx.doi.org/10.1200/JCO.2005.00.992

Mitsudomi T, Morita S, Yatabe Y, 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 2010; 11: 121-8. http://dx.doi.org/10.1016/S1470-2045(09)70364-X

Maemondo M, Inoue A, Kobayashi K, et al. Gefitinib or chemotherapy for non-small-cell lung cancer with mutated EGFR. N Engl J Med 2010; 362: 2380-8. http://dx.doi.org/10.1056/NEJMoa0909530

Zhou C, Wu YL, Chen G, et al. Erlotinib versus chemotherapy as first-line treatment for patients with advanced EGFR mutation-positive non-small-cell lung cancer (OPTIMAL, CTONG-0802): a multicentre, open-label, randomised, phase 3 study. Lancet Oncol 2011; 12: 735-42. http://dx.doi.org/10.1016/S1470-2045(11)70184-X

Rosell R, Carcereny E, Gervais R, 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 2012; 13(3): 239-46.

Inoue A, Kobayashi K, Maemondo M, et al. Final overall survival results of NEJ002, a phase III trial comparing gefitinib to carboplatin (CBDCA) plus paclitaxel (TXL) as the first-line treatment for advanced non-small cell lung cancer (NSCLC) with EGFR mutations. J Clin Oncol 2011; 29(suppl): abstr 7519.

Takano T, Fukui T, Ohe Y, et al. EGFR mutations predict survival benefit from gefitinib in patients with advanced lung adenocarcinoma: a historical comparison of patients treated before and after gefitinib approval in Japan. J Clin Oncol 2008; 26: 5589-95. http://dx.doi.org/10.1200/JCO.2008.16.7254

Kosaka T, Yatabe Y, Onozato R, Kuwano H, Mitsudomi T. Prognostic implication of EGFR, KRAS, and TP53 gene mutations in a large cohort of Japanese patients with surgically treated lung adenocarcinoma. J Thorac Oncol 2009; 4: 22-9. http://dx.doi.org/10.1097/JTO.0b013e3181914111

Sasaki H, Shimizu S, Endo K, et al. EGFR and erbB2 mutation status in Japanese lung cancer patients. Int J Cancer 2006; 118: 180-4. http://dx.doi.org/10.1002/ijc.21301

Marks JL, Broderick S, Zhou Q, et al. Prognostic and therapeutic implications of EGFR and KRAS mutations in resected lung adenocarcinoma. J Thorac Oncol 2008; 3: 111-6. http://dx.doi.org/10.1097/JTO.0b013e318160c607

Zhu CQ, da Cunha Santos G, Ding K, et al. Role of KRAS and EGFR as biomarkers of response to erlotinib in National Cancer Institute of Canada Clinical Trials Group Study BR.21. J Clin Oncol 2008; 26: 4268-75. http://dx.doi.org/10.1200/JCO.2007.14.8924

Cappuzzo F, Ciuleanu T, Stelmakh L, 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. http://dx.doi.org/10.1016/S1470-2045(10)70112-1

Katayama T, Matsuo K, Kosaka T, Sueda T, Yatabe Y, Mitsudomi T. Effect of gefitinib on the survival of patients with recurrence of lung adenocarcinoma after surgery: a retrospective case-matching cohort study. Surg Oncol 2010; 19: e144-9. http://dx.doi.org/10.1016/j.suronc.2010.07.002

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Published

2012-01-28

How to Cite

Kenichi Suda, Simon Ito, Hiroshi Mizuuchi, Yoshihiko Maehara, Yasushi Yatabe, & Tetsuya Mitsudomi. (2012). EGFR Tyrosine Kinase Inhibitors Prolong Overall Survival in EGFR Mutated Non-Small-Cell Lung Cancer Patients with Postsurgical Recurrence . Journal of Cancer Research Updates, 1(1),  102–107. https://doi.org/10.6000/1929-2279.2012.01.01.15

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