바로가기메뉴

본문 바로가기 주메뉴 바로가기

Tuberculosis & Respiratory Diseases

Article Contents

Next
e-Submission

Vol.73 No.6
Citation Share

Gefitinib in Selected Patients with Pre-Treated Non-Small-Cell Lung Cancer: Results from a Phase IV, Multicenter, Non-Randomized Study (SELINE)

Tuberculosis & Respiratory Diseases / Tuberculosis & Respiratory Diseases,
2012, v.73 no.6, pp.303-311











& (2012). Gefitinib in Selected Patients with Pre-Treated Non-Small-Cell Lung Cancer: Results from a Phase IV, Multicenter, Non-Randomized Study (SELINE). Tuberculosis & Respiratory Diseases, 73(6), 303-311.
  • Downloaded
  • Viewed
PDF Download

Abstract

Background: This study was designed to analyze the efficacy of gefitinib as a second-line therapy, according to the clinical characteristics in Korean patients with non-small-cell lung cancer (NSCLC). Methods: In this Phase IV observational study, we recruited patients, previously failed first-line chemotherapy, who had locally advanced or metastatic NSCLC, and who were found to be either epidermal growth factor receptor(EGFR) mutation-positive or satisfied 2 or more of the 3 characteristics: adenocarcinoma, female, and non-smoker. These patients were administered with gefitinib 250 mg/day, orally. The primary endpoints were to evaluate the objective response rate (ORR) and to determine the relationship of ORRs, depending on each patient's characteristics of modified intent-to-treat population. Results: A total of 138 patients participated in this study. One subject achieved complete response, and 42 subjects achieved partial response (ORR, 31.2%). The subgroup analysis demonstrated that the ORR was significantly higher in patients with EGFR mutation-positive, compared to that of EGFR mutation-negative (45.8% vs. 14.0%, p=0.0004). In a secondary efficacy variable, the median progression-free survival (PFS) was 5.7 months (95% confidence interval, 3.9∼8.4 months) and the 6-month PFS and overall survival were 49.6% and 87.9%, respectively. The most common reported adverse events were rash (34.4%), diarrhea (26.6%), pruritus (17.5%), and cough (15.6%). Conclusion: Gefitinib was observed in anti-tumor activity with favorable tolerability profile as a second-line therapy in these selected patients. When looking at EGFR mutation status, EGFR mutation-positive showed strong association with gefitinib by greater response and prolonged PFS, compared with that of EGFR mutation-negative.

keywords
Gefitinib, Receptor, Epidermal Growth Factor, Mutation, Carcinoma, Non-Small-Cell Lung, Disease-Free Survival

Reference

1.

1. Jang TW, Oak CH, Chang HK, Suo SJ, Jung MH. EGFR and KRAS mutations in patients with adenocarcinoma of the lung. Korean J Intern Med 2009;24:48-54.

2.

2. Zhang XT, Li LY, Mu XL, Cui QC, Chang XY, Song W, et al. The EGFR mutation and its correlation with response of gefitinib in previously treated Chinese patients with advanced non-small-cell lung cancer. Ann Oncol 2005;16:1334-42.

3.

3. Han SW, Kim TY, Hwang PG, Jeong S, Kim J, Choi IS, et al. Predictive and prognostic impact of epidermal growth factor receptor mutation in non-small-cell lung cancer patients treated with gefitinib. J Clin Oncol 2005;23:2493-501.

4.

4. Han SW, Hwang PG, Chung DH, Kim DW, Im SA, Kim YT, et al. Epidermal growth factor receptor (EGFR) downstream molecules as response predictive markers for gefitinib (Iressa, ZD1839) in chemotherapy-resistant non-small cell lung cancer. Int J Cancer 2005;113:109- 15.

5.

5. Hong J, Kyung SY, Lee SP, Park JW, Jung SH, Lee JI, et al. Pemetrexed versus gefitinib versus erlotinib in previously treated patients with non-small cell lung cancer. Korean J Intern Med 2010;25:294-300.

6.

6. Park K, Goto K. A review of the benefit-risk profile of gefitinib in Asian patients with advanced non-small-cell lung cancer. Curr Med Res Opin 2006;22:561-73.

7.

7. Thatcher N, Chang A, Parikh P, Rodrigues Pereira J, Ciuleanu T, von Pawel J, et al. 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 2005;366:1527-37.

8.

8. Lynch TJ, Bell DW, Sordella R, Gurubhagavatula S, Okimoto RA, Brannigan BW, 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.

9.

9. Paez JG, Jänne PA, Lee JC, Tracy S, Greulich H, Gabriel S, et al. EGFR mutations in lung cancer: correlation with clinical response to gefitinib therapy. Science 2004;304:1497-500.

10.

10. Pao W, Miller V, Zakowski M, Doherty J, Politi K, Sarkaria I, et al. 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 2004;101:13306-11.

11.

11. Fukuoka M, Wu YL, Thongprasert S, Sunpaweravong P, Leong SS, Sriuranpong V, et al. Biomarker analyses and final overall survival results from a phase III, randomized, open-label, first-line study of gefitinib versus carboplatin/paclitaxel in clinically selected patients with advanced non-small-cell lung cancer in Asia (IPASS). J Clin Oncol 2011;29:2866-74.

12.

12. Kim ES, Hirsh V, Mok T, Socinski MA, Gervais R, Wu YL, et al. Gefitinib versus docetaxel in previously treated non-small-cell lung cancer (INTEREST): a randomised phase III trial. Lancet 2008;372:1809-18.

13.

13. Therasse P, Arbuck SG, Eisenhauer EA, Wanders J, Kaplan RS, Rubinstein L, et al. 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 2000;92:205-16.

14.

14. Fukuoka M, Yano S, Giaccone G, Tamura T, Nakagawa K, Douillard JY, et al. Multi-institutional randomized phase II trial of gefitinib for previously treated patients with advanced non-small-cell lung cancer (The IDEAL 1 Trial) [corrected]. J Clin Oncol 2003;21:2237-46.

15.

15. Kris MG, Natale RB, Herbst RS, Lynch TJ Jr, Prager D, Belani CP, et al. Efficacy of gefitinib, an inhibitor of the epidermal growth factor receptor tyrosine kinase, in symptomatic patients with non-small cell lung cancer: a randomized trial. JAMA 2003;290:2149-58.

16.

16. Cohen MH, Williams GA, Sridhara R, Chen G, Pazdur R. FDA drug approval summary: gefitinib (ZD1839) (Iressa) tablets. Oncologist 2003;8:303-6.

17.

17. Wu JY, Yu CJ, Yang CH, Wu SG, Chiu YH, Gow CH, et al. First- or second-line therapy with gefitinib produces equal survival in non-small cell lung cancer. Am J Respir Crit Care Med 2008;178:847-53.

Tuberculosis & Respiratory Diseases

e-Submission OA Policy