Clinical Outcomes and Prognostic Factors Associated with the Response to Erlotinib in Non-Small-Cell Lung Cancer Patients with Unknown EGFR Mutational Status

  • Aydiner, Adnan (Department of Medical Oncology, Istanbul University Institute of Oncology) ;
  • Yildiz, Ibrahim (Department of Medical Oncology, Istanbul University Institute of Oncology) ;
  • Seyidova, Avesta (Department of Medical Oncology, Istanbul University Institute of Oncology)
  • Published : 2013.05.30


Background: The efficacy of erlotinib is controversial in patients with unknown EGFR mutational status. The aim of this study was to identify the clinicopathological factors that are predictive of erlotinob treatment outcomes for NSCLC patients with unknown EGFR mutational status. Materials and Methods: A retrospective analysis of 109 patients with advanced NSCLC who had previously failed at least one line of chemotherapy and received subsequent treatment with erlotinib (150 mg/day orally) was performed. A Cox proportional hazard model for univariate and multivariate analyses was used to identify the baseline clinical parameters correlating with treatment outcome, expressed in terms of hazard ratios (HRs) and 95% confidence intervals. Results: The median treatment duration was 15 weeks (range, 4-184). The disease control rate was 55%, including disease stability for ${\geq}3$ months for 40% of the patients. Median progression-free survival and median overall survival (OS) were 4.2 and 8.5 months, respectively. The Cox model indicated that an Eastern Cooperative Oncology Group performance status (ECOG PS) ${\geq}2$ (HR 3.82; p<0.001), presence of intra-abdominal metastasis (HR 3.42; p=0.002), 2 or more prior chemotherapy regimens (HR 2.29; p=0.021), and weight loss >5% (HR 2.05; p=0.034) were independent adverse prognostic factors for OS in NSCLC patients treated with erlotinib. Conclusions: This study suggests that NSCLC patients should be enrolled in erlotinib treatment after a first round of unsuccessful chemotherapy to improve treatment success, during which they should be monitored for intra-abdominal metastasis and weight loss.


  1. Kim ST, Lee J, Sun JM, et al (2010). Prognostic model to predict outcomes in non-small cell lung cancer patients with erlotinib as salvage treatment. Oncology, 79, 78-84.
  2. Massarelli E, Andre F, Liu DD, et al (2003). A retrospective analysis of the outcome of patients who have received two prior chemotherapy regimens including platinum and docetaxel for recurrent non-small-cell lung cancer. Lung Cancer, 39, 55-61.
  3. Mazzoni F, Rotella V, Pratesi N, et al (2011). From clinical trials to clinical practice: predictors of response to erlotinib in advanced non-small cell lung cancer patients pretreated with chemotherapy. Tumori, 97, 160-5.
  4. Miller VA, Kris MG, Shah N, et al (2004). Bronchioloalveolar pathologic subtype and smoking history predict sensitivity to gefitinib in advanced non-small-cell lung cancer. J Clin Oncol, 22,1103-9.
  5. O'Connell JP, Kris MG, Gralla R, et al (1986). Frequency and prognostic importance of pretreatment clinical characteristics in patients with advanced non-small-cell lung cancer treated with combination chemotherapy. J Clin Oncol, 4,1604-14.
  6. Paesmans M, Sculier JP, Libert P, et al (1995). Prognostic factors for survival in advanced non-small-cell lung cancer: univariate and multivariate analyses including recursive partitioning and amalgamation algorithms in 1,052 patients. The European lung cancer working party. J Clin Oncol, 13,1221-30.
  7. Paez JG, Janne PA, Lee JC, et al (2004). EGFR mutations in lung cancer: correlation with clinical response to gefitinib therapy. Science, 304, 1497-500.
  8. Park MJ, Lee J, Hong JY, et al (2009). Prognostic model to predict outcomes in nonsmall cell lung cancer patients treated with gefitinib as a salvage treatment. Cancer, 115, 1518-30.
  9. Parkin DM, Bray F, Ferlay J, Pisani P (2005). Global cancer statistics, 2002. CA Cancer J Clin, 55, 74-108.
  10. Albain KS, Crowley JJ, LeBlanc M, Livingston RB (1991). Survival determinants in extensive-stage non-small-cell lung cancer: the Southwest oncology group experience. J Clin Oncol, 9, 1618-26.
  11. Aoki T, Igawa S, Furuya N, et l (2012). Impacts of treatment lines and initiation timing of erlotinib for advanced non-small cell lung cancer. Anticancer Res, 32, 601-8.
  12. Cappuzzo F, Ciuleanu T, Stelmakh L, et al (2010). Erlotinib as maintenance treatment in advanced non-small-cell lung cancer: a multicentre, randomised, placebo-controlled phase 3 study. Lancet Oncol, 11, 521-9.
  13. Ciardiello F, Tortora G (2008). EGFR antagonists in cancer treatment. N Engl J Med, 358, 1160-74.
  14. Ciuleanu T, Stelmakh L, Cicenas S, et al (2012). Efficacy and safety of erlotinib versus chemotherapy in secondline treatment of patients with advanced, non-small-cell lung cancer with poor prognosis (TITAN): a randomised multicentre, open-label, phase 3 study. Lancet Oncol, 13, 300-8.
  15. De Maio E, Tibaldi C, D'Incecco A, et al (2010). Consequences of targeted treatments for second-line therapy. Ann Oncol, 21, 234-40.
  16. Eberhard DA, Johnson BE, Amler LC, et al (2005). Mutations in the epidermal growth factor receptor and in KRAS are predictive and prognostic indicators in patients with nonsmall-cell lung cancer treated with chemotherapy alone and in combination with erlotinib. J Clin Oncol, 23, 5900-9.
  17. Florescu M, Hasan B, Seymour L, Ding K, Shepherd FA (2008). A clinical prognostic index for patients treated with erlotinib in National Cancer Institute of Canada Clinical Trials Group study BR.21. J Thorac Oncol, 3, 590-8.
  18. 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, 706-14.
  19. Hoang T, Xu R, Schiller JH, Bonomi P, Johnson DH (2005). Clinical model to predict survival in chemonaive patients with advanced non-small-cell lung cancer treated with third-generation chemotherapy regimens based on eastern cooperative oncology group data. J Clin Oncol, 23, 175-83.
  20. Hsu CL, Chen KY, Shih JY, et al (2012). Advanced non-small cell lung cancer in patients aged 45 years or younger: outcomes and prognostic factors. BMC Cancer, 12, 241.
  21. Ahn MJ, Park BB, Ahn JS, et al (2008). Are there any ethnic differences in molecular predictors of erlotinib efficacy in advanced non-small cell lung cancer? Clin Cancer Res, 14, 3860-6.
  22. Ailawadhi S, Derby L, Natarajan R, et al (2009). Erlotinib for metastatic non-small-cell lung cancer: first-, second- or thirdline setting - does it matter ? A single-institution experience. Oncology, 76, 85-90.
  23. Karam I, Melosky B (2012). Response to second-line erlotinib in an EGFR mutation-negative patient with non-small-cell lung cancer: make no assumptions. Curr Oncol, 19, 42-6.
  24. Schlessinger J (2000). Cell signaling by receptor tyrosine kinases. Cell, 103, 211-25.
  25. Shepherd FA, Rodrigues Pereira J, Ciuleanu T, et al (2005). Erlotinib in previously treated non-small-cell lung cancer. N Engl J Med, 353, 123-32.
  26. Thatcher N, Chang A, Parikh P, et al (2005). Gefitinib plus best supportive care in previously treated patients with refractory advanced non-small-cell lung cancer: results from a randomised, placebo-controlled, multicentre study (Iressa Survival Evaluation in Lung Cancer). Lancet, 366, 1527-37.
  27. Therasse P, Arbuck SG, Eisenhauer EA, et al (2000). New guidelines to evaluate the response to treatment in solid tumors. European organization for research and treatment of cancer, national cancer institute of the United States, national cancer institute of Canada. J Natl Cancer Inst, 92, 205-16.
  28. Trotti A, Colevas AD, Setser A, et al (2003). CTCAE v3.0: development of a comprehensive grading system for the adverse effects of cancer treatment. Semin Radiat Oncol, 13, 176-81.
  29. Tsao MS, Sakurada A, Cutz JC, et al (2005) Erlotinib in lung cancer - molecular and clinical predictors of outcome. N Engl J Med, 353, 133-44.
  30. Uhm JE, Park BB, Ahn MJ et al (2009). Erlotinib monotherapy for stage IIIB/IV non-small cell lung cancer: a multicenter trial by the Korean cancer study group. J Thorac Oncol, 4, 1136-43.
  31. Veale D, Kerr N, Gibson GJ, Kelly PJ, Harris AL (1993). The relationship of quantitative epidermal growth factor receptor expression in non-small cell lung cancer to long term survival. Br J Cancer, 68, 162-5.

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