Gefitinib as first line therapy in Malaysian patients with EGFR mutation-positive non-small-cell lung cancer: A single-center retrospective study

Abdullah,Matin  Mellor; Bhat,Amit; Mohamed,Ahmad  Kamal; Ching,Foo  Yoke; Ahmed,Nida; Gantotti,Sandeep

doi:10.3892/ol.2016.4322

Gefitinib as first line therapy in Malaysian patients with EGFR mutation-positive non-small-cell lung cancer: A single-center retrospective study

Authors:
- Matin Mellor Abdullah
- Amit Bhat
- Ahmad Kamal Mohamed
- Foo Yoke Ching
- Nida Ahmed
- Sandeep Gantotti
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Affiliations: Department of Clinical Oncology and Radiotherapy, Subang Jaya Medical Centre, Subang Jaya 47500, Selangor, Malaysia, Indegene Lifesystems Pvt. Ltd., Nagavara, Karnataka 560045, Bangalore, India
Published online on: March 9, 2016 https://doi.org/10.3892/ol.2016.4322
Pages: 2757-2762
Copyright: © Abdullah et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The present retrospective, single-center study evaluated the objective response rate (ORR) and progression-free survival (PFS) of epidermal growth factor receptor (EGFR) mutation-positive Malaysian patients with advanced lung adenocarcinoma treated with gefitinib. During May 2008 to July 2013, 33 patients with Stage IV, EGFR mutation-positive non-small-cell lung cancer (NSCLC) were identified and received gefitinib (250 mg) as first line treatment. The primary and secondary end points were ORR, PFS and safety, respectively. A total of 18 (54.5%) and 2 (6.1%) patients achieved partial response (PR) and complete response (CR) to gefitinib therapy, respectively, yielding an ORR of 60.6% (95% CI, 42.1‑77.1%). Patients with exon 20 or 21 mutations (n=6, 66.7%) tended to have better ORR compared with exon 19 (n=22, 59.1%). The median PFS was 8.9 months in Malaysian patients with EGFR mutation‑positive NSCLC, treated with gefitinib. The majority of treatment‑related toxicity was mild in nature. The most frequently reported adverse events included dry skin (39.4%), skin rash (27.2%), and dermatitis acneiform (15.2%). In conclusion, Malaysian patients with locally advanced and metastatic EGFR mutation‑positive NSCLC responded favorably to gefitinib therapy in terms of ORR, median PFS, and tolerability, the results of which were consistent with those of the IPASS study conducted in an Asian population. Considering the efficacy and safety profile of gefitinib, it is a favorable option for the first‑line treatment of Malaysian patients with EGFR mutation‑positive NSCLC. However, future long‑term studies in a larger population of Malaysian patients are required to support whether the prolonged PFS conferred by gefitinib will translate into prolonged overall survival.

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1	Liam CK, Pang YK, Leow CH, et al: Changes in the distribution of lung cancer cell types and patient demography in a developing multiracial Asian country: Experience of a university teaching hospital. Lung Cancer. 53:23–30. 2006. View Article : Google Scholar : PubMed/NCBI
2	National Cancer Registry (2007). Malaysia Cancer Statistics - Data and Figure, National Cancer Registry, Malaysia. http://www.care.upm.edu.my/dokumen/13603_NCR2007.pdfAccessed. September 08–2014
3	National Comprehensive Cancer Network: 2011 NCCN Clinical Practice Guidelines in Oncology: Non-small Cell Lung Cancer, Version 1. National Comprehensive Cancer Network (2011) NCCN Clinical Practice Guidelines in Oncology. 2011.http://www.nccn.org/patients/guidelines/nscl/index.htmlAccessed. September 08–2014
4	Liam CK, Leow HR, How SH, Pang YK, Chua KT, Lim BK, Lai NL, Kuan YC, Pailoor J and Rajadurai P: Epidermal growth factor receptor mutations in non-small cell lung cancers in a multiethnic malaysian patient population. Asian Pac J Cancer Prev. 15:321–326. 2014. View Article : Google Scholar : PubMed/NCBI
5	Ho C, Murray N, Laskin J, Melosky B, Anderson H and Bebb G: Asian ethnicity and adenocarcinoma histology continues to predict response to gefitinib in patients treated for advanced non-small cell carcinoma of the lung in North America. Lung Cancer. 49:225–231. 2005. View Article : Google Scholar : PubMed/NCBI
6	Mok TS, Wu YL, Thongprasert S, Yang CH, Chu DT, Saijo N, Sunpaweravong P, Han B, Margono B, Ichinose Y, et al: Gefitinib or carboplatin-paclitaxel in pulmonary adenocarcinoma. N Engl J Med. 361:947–957. 2009. View Article : Google Scholar : PubMed/NCBI
7	Mitsudomi T, Morita S, Yatabe Y, Negoro S, Okamoto I, Tsurutani J, Seto T, Satouchi M, Tada H, Hirashima T, 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. 11:121–128. 2010. View Article : Google Scholar : PubMed/NCBI
8	Maemondo M, Inoue A, Kobayashi K, Sugawara S, Oizumi S, Isobe H, Gemma A, Harada M, Yoshizawa H, Kinoshita I, et al: Gefitinib or chemotherapy for non-small-cell lung cancer with mutated EGFR. N Engl J Med. 362:2380–2388. 2010. View Article : Google Scholar : PubMed/NCBI
9	Yang CH, Yu CJ, Shih JY, Chang YC, Hu FC, Tsai MC, Chen KY, Lin ZZ, Huang CJ, Shun CT, et al: Specific EGFR mutations predict treatment outcome of stage IIIB/IV patients with chemotherapy-naive non-small-cell lung cancer receiving first-line gefitinib monotherapy. J Clin Oncol. 26:2745–2753. 2008. View Article : Google Scholar : PubMed/NCBI
10	Chang A, Parikh P, Thongprasert S, Tan EH, Perng RP, Ganzon D, Yang CH, Tsao CJ, Watkins C, Botwood N and Thatcher N: Gefitinib (IRESSA) in patients of Asian origin with refractory advanced non-small cell lung cancer: Subset analysis from the ISEL study. J Thorac Oncol. 1:847–855. 2006. View Article : Google Scholar : PubMed/NCBI
11	Liam CK, Ruthranesan M, Lee CH, Pang YK, Chua KT and Lim BK: Outcomes of Malaysian patients with advanced lung adenocarcinoma and unknown epidermal growth factor receptor mutation status treated with gefitinib. Asia Pac J Clin Oncol. 8:267–274. 2012. View Article : Google Scholar : PubMed/NCBI
12	Liam CK, Pang YK and Leow CH: Epidermal growth factor receptor targeted therapy with gefitinib in locally advanced and metastatic primary lung adenocarcinoma. Respirology. 11:287–291. 2006. View Article : Google Scholar : PubMed/NCBI
13	Fukuoka M, Yano S, Giaccone G, Tamura T, Nakagawa K, Douillard JY, Nishiwaki Y, Vansteenkiste J, Kudoh S, Rischin D, 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. 21:2237–2246. 2003. View Article : Google Scholar : PubMed/NCBI
14	Kris MG, Natale RB, Herbst RS, Lynch TJ Jr, Prager D, Belani CP, Schiller JH, Kelly K, Spiridonidis H, Sandler A, 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. 290:2149–2158. 2003. View Article : Google Scholar : PubMed/NCBI
15	Thatcher N, Chang A, Parikh P, Pereira Rodrigues J, Ciuleanu T, von Pawel J, Thongprasert S, Tan EH, Pemberton K, Archer V and Carroll K: 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. 366:1527–1537. 2005. View Article : Google Scholar : PubMed/NCBI
16	Lynch TJ, Bell DW, Sordella R, Gurubhagavatula S, Okimoto RA, Brannigan BW, Harris PL, Haserlat SM, Supko JG, Haluska FG, et al: Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small-cell lung cancer to gefitinib. N Engl J Med. 350:2129–2139. 2004. View Article : Google Scholar : PubMed/NCBI
17	Morita S, Okamoto I, Kobayashi K, Yamazaki K, Asahina H, Inoue A, Hagiwara K, Sunaga N, Yanagitani N, Hida T, et al: Combined survival analysis of prospective clinical trials of gefitinib for non-small cell lung cancer with EGFR mutations. Clin Cancer Res. 15:4493–4498. 2009. View Article : Google Scholar : PubMed/NCBI
18	Kim ES, Hirsh V, Mok T, Socinski MA, Gervais R, Wu YL, Li LY, Watkins CL, Sellers MV, Lowe ES, et al: Gefitinib versus docetaxel in previously treated non-small-cell lung cancer (INTEREST): A randomised phase III trial. Lancet. 372:1809–1818. 2008. View Article : Google Scholar : PubMed/NCBI
19	Miller VA, Kris MG, Shah N, Patel J, Azzoli C, Gomez J, Krug LM, Pao W, Rizvi N, Pizzo B, et al: Bronchioloalveolar pathologic subtype and smoking history predict sensitivity to gefitinib in advanced non-small-cell lung cancer. J Clin Oncol. 22:1103–1109. 2004. View Article : Google Scholar : PubMed/NCBI
20	Iuchi T, Shingyoji M, Sakaida T, Hatano K, Nagano O, Itakura M, Kageyama H, Yokoi S, Hasegawa Y, Kawasaki K and Iizasa T: Phase II trial of gefitinib alone without radiation therapy for Japanese patients with brain metastases from EGFR-mutant lung adenocarcinoma. Lung Cancer. 82:282–287. 2013. View Article : Google Scholar : PubMed/NCBI