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. 2018 Jan 16;1(1):CD006847.
doi: 10.1002/14651858.CD006847.pub2.

Gefitinib for advanced non-small cell lung cancer

Esther Ha Sim  1 , Ian A Yang, Richard Wood-Baker, Rayleen V Bowman, Kwun M Fong
Affiliations

Gefitinib for advanced non-small cell lung cancer

Esther Ha Sim et al. Cochrane Database Syst Rev. .

Abstract

Background: The role of gefitinib for the treatment of advanced non-small cell lung cancer (NSCLC) is evolving. We undertook a systematic review to evaluate the available evidence from all randomised trials.

Objectives: To determine the effectiveness and safety of gefitinib as first-line, second-line or maintenance treatment for advanced NSCLC.

Search methods: We performed searches in CENTRAL, MEDLINE and Embase from inception to 17 February 2017. We handsearched relevant conference proceedings, clinical trial registries and references lists of retrieved articles.

Selection criteria: We included trials assessing gefitinib, alone or in combination with other treatment, compared to placebo or other treatments in the first- or successive-line treatment of patients with NSCLC, excluding compassionate use.

Data collection and analysis: We used the standard Cochrane methodology. Two authors independently assessed the search results to select those with sound methodological quality. We carried out all analyses on an intention-to-treat basis. We recorded the following outcome data: overall survival, progression-free survival, toxicity, tumour response and quality of life. We also collected data for the following subgroups: Asian ethnicity and positive epidermal growth factor receptor (EGFR) mutation.

Main results: We included 35 eligible randomised controlled trials (RCTs), which examined 12,089 patients.General populationGefitinib did not statistically improve overall survival when compared with placebo or chemotherapy in either first- or second-line settings. Second-line gefitinib prolonged time to treatment failure (TTF) (hazard ratio (HR) 0.82, 95% confidence interval (CI) 0.75 to 0.90, P < 0.0001) when compared with placebo. Maintenance gefitinib improved progression-free survival (HR 0.70, 95% CI 0.53 to 0.91, P = 0.007) after first-line therapy.Studies in patients of Asian ethnicity or that conducted subgroup analysesSecond-line gefitinib prolonged overall survival over placebo (HR 0.66, 95% CI 0.48 to 0.91, P = 0.01). In the first-line setting, progression-free survival was improved with gefitinib over chemotherapy alone (HR 0.65, 95% CI 0.43 to 0.98, P = 0.04, moderate quality of evidence). Gefitinib given in combination with a chemotherapy regimen improved progression-free survival versus either gefitinib alone or chemotherapy alone (HR 0.69, 95% CI 0.49 to 0.96, P = 0.03; HR 0.69, 95% CI 0.62 to 0.77, P < 0.00001, respectively). In the second-line setting, progression-free survival was superior in patients given gefitinib over placebo or chemotherapy (HR 0.69, 95% CI 0.52 to 0.91, P = 0.009; HR 0.71, 95% CI 0.57 to 0.88, P = 0.002; moderate quality of evidence, respectively). Combining gefitinib with chemotherapy in the second-line setting was superior to gefitinib alone (HR 0.65, 95% CI 0.43 to 0.97, P = 0.04). As maintenance therapy, gefitinib improved progression-free survival when compared with placebo (HR 0.42, 95% CI 0.33 to 0.54, P < 0.00001).Patients with EGFR mutation-positive tumoursStudies in patients with EGFR mutation-positive tumours showed an improvement in progression-free survival in favour of gefitinib over first-line and second-line chemotherapy (HR 0.47, 95% CI 0.36 to 0.61, P < 0.00001; HR 0.24, 95% CI 0.12 to 0.47, P < 0.0001, respectively). Gefitinib as maintenance therapy following chemotherapy improved overall and progression-free survival (HR 0.39, 95% CI 0.15 to 0.98, P = 0.05; HR 0.17, 95% CI 0.07 to 0.41, P < 0.0001, respectively) in one phase III study when compared to placebo.Toxicities from gefitinib included skin rash, diarrhoea and liver transaminase derangements. Toxicities from chemotherapy included anaemia, neutropenia and neurotoxicity.In terms of quality of life, gefitinib improved Functional Assessment of Cancer Therapy-Lung (FACT-L) (standardised mean difference (SMD) 10.50, 95% CI 9.55 to 11.45, P < 0.000001), lung cancer subscale (SMD 3.63, 95% CI 3.08 to 4.19, P < 0.00001) and Trial Outcome Index (SMD 9.87, 95% CI 1.26 to 18.48, P < 0.00001) scores when compared with chemotherapy.

Authors' conclusions: This systematic review shows that gefitinib, when compared with standard first- or second-line chemotherapy or maintenance therapy, probably has a beneficial effect on progression-free survival and quality of life in selected patient populations, particularly those with tumours bearing sensitising EGFR mutations.Patients with EGFR mutations lived longer when given maintenance gefitinib than those given placebo.One study conducted subgroup analysis and showed that gefitinib improved overall survival over placebo in the second-line setting in patients of Asian ethnicity. All other studies did not detect any benefit on overall survival. The data analysed in this review were very heterogenous. We were limited in the amount of data that could be pooled, largely due to variations in study design. The risk of bias in most studies was moderate, with some studies not adequately addressing potential selection, attrition and reporting bias. This heterogeneity may have an impact on the applicability of the resultsCombining gefitinib with chemotherapy appears to be superior in improving progression-free survival to either gefitinib or chemotherapy alone, however further data and phase III studies in these settings are required.Gefitinib has a favourable toxicity profile when compared with current chemotherapy regimens. Although there is no improvement in overall survival, gefitinib compares favourably with cytotoxic chemotherapy in patients with EGFR mutations with a prolongation of progression-free survival and a lesser side effect profile.

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Conflict of interest statement

Esther HA Sim (ES): none known

Ian A Yang (IY): none known

Rayleen V Bowman (RB) has received pharmaceutical company sponsored items, meals and travel expenses associated with attendance at scientific meetings including Australian Lung Cancer Conference and Thoracic Society of Australia and New Zealand. RB is a current member of the Lung Foundation (Australia)'s Lung Cancer Consultative Group, which receives financial sponsorship from a number of pharmaceutical companies.

Kwun M Fong (KF) was an investigator for a clinical trial of gefitinib for lung cancer (Astra Zeneca international trial) ‐ funding received by the Hospital funds the clinical trial and the employment of a trials nurse. KF's laboratory has also undertaken contract research for a clinical study looking at immunohistochemistry of certain proteins in lung cancer for Novartis ‐ funding received will go to the Project and employment of Research staff for the Project. KF was previously offered an honorarium from a pharmaceutical company for attending an one‐off Advisory Board Meeting; this was not accepted and asked to be given to a charity. KF has received occasional pens, pads and minor stationery from industry. KF has occasionally attended/spoken at meetings organised by pharmaceutical companies where meals/travel costs would be sponsored. KF has organised the Queensland Lung Cancer Interest Group Meeting (two to three meetings per year, a teleconference meeting, which is supported by Eli Lilly. KF has/is also involved in organising and attending professional meetings including those run by the Thoracic Society of Australia and New Zealand, Asia‐Pacific Society of Respirology, Australian Lung Cancer Conference, IASLC, where some sponsorship is usually provided by industry. KF is involved with the Lung Foundation (Australia)'s Lung Cancer Cooperative Group (not‐for‐profit, public benevolent institution) (http://www.lungnet.org/www.lungnet.org.au) and its activities, which includes promotion of Cochrane Reviews. The LFA receives support from pharmaceutical companies. KF was Chair of the Australian Lung Cancer trials Group, which receives some support funding from pharmaceutical companies.

Richard Wood‐Baker (RWB): none known

Figures

1
1
Study flow diagram for searches 1966‐2017. (EGFR: epidermal growth factor receptor)
2
2
'Risk of bias' summary: review authors' judgements about each risk of bias item for each included study.
3
3
Progression‐free survival: Gefitinib versus first‐line chemotherapy in an Asian population (Analysis 5.4).
4
4
Progression‐free survival: Gefitinib versus second‐line chemotherapy in an Asian population (Analysis 5.5).
5
5
Progression‐free survival: Gefitinib versus first‐line chemotherapy in an EGFR mutation positive population (Analysis 6.3).
6
6
Progression‐free survival: Gefitinib versus second‐line chemotherapy in an EGFR mutation positive population (Analysis 6.4).
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References

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Sun 2012 KCSG‐LU08‐01 {published data only}
    1. Ahn M, Sun J, Ahn JS, Kim S, Min YJ, Yun HJ, et al. Randomized phase III trial of gefitinib or pemetrexed as second‐line treatment in patients with non‐small cell lung cancer previously treated with platinum‐based chemotherapy (KCSG‐LU08‐01). ASCO Annual Meeting 2011 Chicago, IL United States. American Society of Clinical Oncology, 2011; Vol. 29.
    1. Ahn MJ, Sun JM, Lee KH, Ahn JS, Kim SW, Min YJ, et al. Randomized phase III trial of gefitinib or pemetrexed as second‐line treatment in patients with non‐small cell lung cancer previously treated with platinum‐based chemotherapy (KCSG‐LU08‐01). 14th World Conference on Lung Cancer Amsterdam Netherlands. International Association for the Study of Lung Cancer, 2011; Vol. 6:S317.
    1. Sun JM, Lee KH, Kim SW, Lee DH, Min YJ, Yun HJ, et al. Gefitinib versus pemetrexed as second‐line treatment in patients with nonsmall cell lung cancer previously treated with platinum‐based chemotherapy (KCSG‐LU08‐01): an open‐label, phase 3 trial. Cancer 2012;118:6234‐42. - PubMed
Takeda 2010 WJTOG0203 {published data only}
    1. Okamoto I, Hida T, Kashii T, et al. Randomized phase III study of platinum‐doublet chemotherapy followed by gefitinib versus continued platinum‐doublet chemotherapy in patients (pts) with advanced non‐small cell lung cancer (NSCLC): Results of West Japan Thoracic Oncology Group Trial (WJTOG0203) [Abstract No. 2 33PD]. Annals of Oncology 2008;19 Suppl 8:91.
    1. Takeda K, Hida T, Sato T, Ando M, Seto T, Satouchi M, et al. Randomized phase III trial of platinum‐doublet chemotherapy followed by gefitinib comparted with continued platinum‐doublet chemotherapy in Japanese patients with advanced non‐small cell lung cancer: results of a West Japan Thoracic Oncology Group Trial (WJTOG0203). Journal of Clinical Oncology 2010;28(5):753‐60. - PubMed
Thatcher 2005 ISEL {published data only}
    1. Chang A, Parikh P, Thongprasert S, Tan EH, Perng RP, Ganzon D, et al. Gefitinib (IRESSA) in patients of Asian origin with refractory advanced non‐small cell lung cancer: subset analysis from the ISEL study. Journal of Thoracic Oncology 2006;1(8):847‐55. - PubMed
    1. Hirsch FR, Dziadziuszko R, Thatcher N, Mann H, Watkins C, Parums DV, et al. Epidermal growth factor receptor immunohistochemistry: comparison of antibodies and cutoff points to predict benefit from gefitinib in a phase 3 placebo‐controlled study in advanced non small‐cell lung cancer. Cancer 2008;112(5):1114‐21. - PMC - PubMed
    1. Hirsch FR, Varella‐Garcia M, Bunn Jr PA, Franklin WA, Dziadziuszko R, Thatcher N, et al. Molecular predictors of outcome with gefitinib in a phase III placebo‐controlled study in advanced non‐small cell lung cancer. Journal of Clinical Oncology 2006;24(31):5034‐42. - PubMed
    1. Thatcher N, Chang A, Parikh P, Rodrigues Pereira J, Ciuleanu T, 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(9496):1527‐37. - PubMed
Xu 2015 {published data only}
    1. Xu YH, Mei JS, Zhou J. Randomized study of gefitinib versus pemetrexed as maintenance treatment in patients with advanced glandular non‐small cell lung cancer. International Journal of Clinical and Experimental Medicine 2015;8(4):6242‐6. - PMC - PubMed
Xue 2015 {published data only}
    1. Xue C, Hong S, Li N, Feng W, Jia J, Peng J, et al. Randomized, multicenter study of gefitinib dose‐escalation in advanced non‐small‐cell lung cancer patients achieved stable disease after one‐month gefitinib treatment. Scientific Reports 2015;5:10648. - PMC - PubMed
    1. Zhang L, Xue C, Li N, Feng W, Jia J, Peng J, et al. Randomized, open‐label, multi‐center study of gefitinib dose‐escalation (500mg/d versus 250mg/d) in advanced NSCLC patient achieved stable disease (SD) after one‐month gefitinib treatment. 15th World Conference on Lung Cancer Sydney, NSW Australia. International Association for the Study of Lung Cancer, 2013; Vol. 8:S1185.
Yang 2014 {published data only}
    1. Boye M, Wang X, Srimuninnimit V, Kang JH, Tsai CM, Orlando M, et al. First‐line pemetrexed plus cisplatin followed by gefitinib maintenance therapy versus gefitinib monotherapy in East Asian never‐smoker patients with locally advanced or metastatic nonsquamous non‐small cell lung cancer: quality of life results from a randomized phase III trial. Clinical Lung Cancer 2016;17(2):150‐60. - PubMed
    1. Kang JH, Ahn M, Kim D, Cho EK, Kim J, Shin SW, et al. Tolerability and outcomes of first‐line pemetrexed‐cisplatin followed by gefitinib maintenance therapy versus gefitinib monotherapy in Korean patients with advanced non‐squamous non‐small cell lung cancer: a post hoc descriptive subgroup analysis of a randomized, phase 3 trial. Cancer Research and Treatment 2015;48(2):458‐64. - PMC - PubMed
    1. Yang JC, Kang JH, Mok T, Ahn M, Srimuninnimit V, Lin C, et al. First‐line pemetrexed plus cisplatin followed by gefitinib maintenance therapy versus gefitinib monotherapy in East Asian patients with locally advanced or metastatic non‐squamous non‐small cell lung cancer: a randomised, phase 3 trial. European Journal of Cancer 2014;50:2219‐30. - PubMed
    1. Yang JC, Park K, Mok TSK, Kang JH, Srimuninnimit V, Lin CC, et al. A randomized phase 3 study comparing first‐line pemetrexed plus cisplatin followed by gefitinib as maintenance with gefitinib monotherapy in east Asian patients with locally advanced or metastatic nonsquamous non‐small cell lung cancer (NSQNSCLC). 15th World Conference on Lung Cancer Sydney, NSW Australia. International Association for the Study of Lung Cancer, 2013; Vol. 8:S288.
    1. Yang JC, Srimuninnimit V, Ahn M, Lin C, Kim S, Tsai C, et al. A randomized phase 3 study comparing first‐line pemetrexed plus cisplatin followed by gefitinib maintenance (PC/G) with gefitinib monotherapy (G) in East Asian patients (pts) with locally advanced or metastatic nonsquamous non‐small cell lung cancer (nSqNSCLC): final survival results. Journal of Clinical Oncology 2015;15 Suppl:8041.
Yu 2014 {published data only}
    1. Yu H, Zhang J, Wu X, Luo Z, Wang H, Sun S, et al. A phase II randomized trial evaluating gefitinib intercalated with pemetrexed/platinum chemotherapy or pemetrexed/platinum chemotherapy alone in unselected patients with advanced non‐squamous non‐small cell lung cancer. Cancer Biology and Therapy 2014;15(7):832‐9. - PMC - PubMed
Zhang 2012 INFORM {published data only}
    1. Yang Y, Ma Y, Zhao Y, Fang W, Hong S, et al. QoL analyses from INFORM study, a phase III study of gefitinib versus placebo as maintenance therapy in advanced NSCLC. Scientific Reports 2015;5:11934. - PMC - PubMed
    1. Zhang L, Ma S, Song X, Han B, Cheng Y, Huang C, et al. Gefitinib versus placebo as maintenance therapy in patients with locally advanced or metastatic non‐small‐cell lung cancer (INFORM; C‐TONG 0804): a multicentre, double‐blind randomised phase 3 trial. Lancet Oncology 2012;13:466‐75. - PubMed
    1. Zhang L, Ma SL, Song XQ, Cheng Y, Huang C, Yang SJ, et al. Pre‐planned subgroup analyses from the phase III, randomised, placebo‐controlled, parallel‐group study of gefitinib (G) as maintenance therapy in patients (pts) with locally advanced or metastatic non‐small‐cell lung cancer (NSCLC) (INFORM; C‐TONG 0804). European Multidisciplinary Cancer Congress Stockholm Sweden. Elsevier Ltd, 2011; Vol. 47:S622‐3.
    1. Zhang L, Ma SL, Song XQ, Han BH, Cheng Y, Huang C, et al. Efficacy, tolerability and biomarker analyses from a phase III, randomized, placebo controlled, parallel group study of gefitinib as maintenance therapy in patients with locally advanced or metastatic non‐small‐cell lung cancer (NSCLC) in China (INFORM) (C‐TONG 0804). 14th World Conference on Lung Cancer Amsterdam Netherlands. International Association for the Study of Lung Cancer, 2011; Vol. 6:S558‐9.
    1. Zhang L, Shenglin M, Song X, Han B, Cheng Y, Huang C, et al. Efficacy, tolerability, and biomarker analyses from a phase III, randomized, placebo‐controlled, parallel group study of gefitinib as maintenance therapy in patients with locally advanced or metastatic non‐small cell lung cancer (NSCLC; INFORM; C‐TONG 0804). ASCO Annual Meeting 2011 Chicago, IL United States. American Society of Clinical Oncology, 2011; Vol. 29.

References to studies excluded from this review

Choi 2015 {published data only}
    1. Choi YJ, Lee DH, Choi CM, Lee JS, Lee SJ, Ahn J, et al. Randomized phase II study of paclitaxel/carboplatin intercalated with gefitinib compared to paclitaxel/carboplatin alone for chemotherapy‐naive non‐small cell lung cancer in a clinically selected population excluding patients with non‐smoking adenocarcinoma or mutated EGFR. BMC Cancer 2015;15:763. - PMC - PubMed
Kim 2012 {published data only}
    1. Kim ST, Uhm JE, Lee J, Sun JM, Sohn I, Kim SW, et al. Randomized phase II study of gefitinib versus erlotinib in patients with advanced non‐small cell lung cancer who failed previous chemotherapy. Lung Cancer 2012;75:82‐8. - PubMed
Lee 2009 {published data only}
    1. Lee KH, Lee KY, Jeon YJ, et al. A phase IV, multicenter, non‐randomized, open‐labelled study to evaluate the efficacy of gefitinib (Iressa®) as a second‐line therapy in Korean patients with non‐small cell lung cancer (NSCLC). Respirology. 2009; Vol. 14 Suppl S3:A161.
Manegold 2005 {published data only}
    1. Manegold C, Gatzemeier U, Buchholz E, Smith RP, Fandi A. A pilot trial of gefitinib in combination with docetaxel in patients with locally advanced or metastatic non‐small‐cell lung cancer. Clinical Lung Cancer 2005;6(6):343‐9. - PubMed
Natale 2009 {published data only}
    1. Natale RB, Bodkin D, Govindan R, Sleckman BG, Rizvi NA, Capo A, et al. Vandetanib versus gefitinib in patients with advanced non‐small‐cell lung cancer: results from a two‐part, double‐blind, randomized phase II study. Journal of Clinical Oncology 2009;27(15):2523‐9. - PubMed
Shi 2013 ICOGEN {published data only}
    1. Shi Y, Zhang L, Liu X, Zhou C, Zhang L, Zhang S, et al. Icotinib versus gefitinib in previously treated advanced non‐small‐cell lung cancer (ICOGEN): a randomised, double‐blind phase 3 non‐inferiority trial. Lancet Oncology 2013;14:953‐61. - PubMed
    1. Sun Y, Shi Y, Zhang L, Liu X, Zhou C, Li Z, et al. Final overall survival and updated biomarker analysis results from the randomized phase III ICOGEN trial. 2012 Annual Meeting of the American Society of Clinical Oncology, ASCO Chicago, IL United States. American Society of Clinical Oncology, 2012; Vol. 30.
    1. Sun Y, Shi Y, Zhang L, Liu X, Zhou C, Wang D, et al. A randomized, doubleblind phase III study of icotinib versus gefitinib in patients with advanced non‐small cell lung cancer (NSCLC) previously treated with chemotherapy (ICOGEN). 14th World Conference on Lung Cancer Amsterdam Netherlands. International Association for the Study of Lung Cancer, 2011; Vol. 6:S317‐8.
Sugawara 2015 {published data only}
    1. Sugawara S, Oizumi S, Minato K, Harada T, Inoue A, Fujita Y, et al. Randomized phase II study of concurrent versus sequential alternating gefitinib and chemotherapy in previously untreated non‐small cell lung cancer with sensitive EGFR mutations: NEJ005/TCOG0902. Annals of Oncology 2015;26:888‐94. - PubMed
Urata 2016 {published data only}
    1. Urata Y, Katakami N, Morita S, Kaji R, Yoshioka H, Seto T, et al. Randomized phase III study comparing gefitinib with erlotinib in patients with previously treated advanced lung adenocarcinoma: WJOG 5108L. Journal of Clinical Oncology 2016;34(27):3248‐57. - PubMed
Zhou 2014 CTONG 0806 {published data only}
    1. Yang J, Cheng Y, Zhao M, Zhou Q, Yan HH, Zhang L, et al. A phase II trial comparing pemetrexed with gefitinib as the second‐line treatment of nonsquamous NSCLC patients with wild‐type EGFR (CTONG0806). 2013 Annual Meeting of the American Society of Clinical Oncology, ASCO Chicago, IL United States. American Society of Clinical Oncology, 2013; Vol. 31.
    1. Zhou Q, Cheng Y, Yang JJ, Zhao MF, Zhang L, Zhang XC, et al. Pemetrexed versus gefitinib as second‐line treatment in advanced non‐squamous nonsmall‐cell lung cancer patients harbouring wild‐type EGFR (CTONG 0806): a multicenter randomized trial. Annals of Oncology 2014;25(12):2385‐91. - PubMed
    1. Zhou Q, Cheng Y, Zhao MF, Yang JJ, Yan H H, Zhang L, et al. Final results of CTONG 0806: a phase II trial comparing pemetrexed with gefitinib as second‐line treatment of advanced non‐squamous NSCLC patients with wild‐type EGFR. 15th World Conference on Lung Cancer Sydney, NSW Australia. International Association for the Study of Lung Cancer, 2013; Vol. 8:S194‐5.

References to ongoing studies

Bhatnagar 2012 {published data only}
    1. Bhatnagar AR, Singh DP, Sharma R, Kumbhaj P. Docetaxel versus geftinib in patients with locally advanced or metastatic NSCLC pretreated with platinum‐based chemotherapy. 4th Australian Lung Cancer Conference, ALCC 2012 Adelaide, SA Australia. International Association for the Study of Lung Cancer, 2012; Vol. 7:S159.
Gaafar 2010 {published data only}
    1. Gaafar RM, Surmont V, Scagliotti G, Klaveren R, Papamichael G, Welch J, et al. A double‐blind, randomized, placebo‐controlled phase III intergroup study of gefitinib (G) in patients (pts) with advanced NSCLC, non‐progressing after first‐line platinum‐based chemotherapy (EORTC 08021‐ILCP 01/03). Journal of Clinical Oncology. 2010; Vol. 28 Suppl 15.
Hong 2010 {published data only}
    1. Hong J, Kyung SY, Lee SP, Park JW, Jung SH, Sym SJ, et al. Randomized phase II study of pemetrexed versus gefitinib for patients with previously treated non‐small cell lung cancer. 4th Asia Pacific Lung Cancer Conference, APLCC 2010 Seoul, South Korea. International Association for the Study of Lung Cancer, 2010; Vol. 5:S401.
Laurie 2000 {published data only}
    1. Laurie SA, Miller VA, Johnson D, Ng KK, Heelan RT, Pizzo BA, et al. Pilot trial of ZD1839 (Iressa‐TM‐), an oral inhibitor of epidermal growth factor receptor (EGFR) tyrosine kinase, in combination with carboplatin (C) and paclitaxel (P) in previously untreated advanced non‐small cell lung cancer. Lung Cancer. 2000; Vol. 29 Suppl 1:S71.
Lee 2013 {published data only}
    1. Lee DH, Kim JE, Choi YJ, Choi CM, Lee JS, Kim SW. Randomized phase II study comparing paclitaxel/carboplatin intercalated with gefitinib to paclitaxel/carboplatin alone for chemotherapy‐naive non‐small cell lung cancer patients either with history of smoking or with wild‐type EGFR. AACR‐NCI‐EORTC International Conference: Molecular Targets and Cancer Therapeutics 2013 Boston, MA United States. American Association for Cancer Research Inc, 2013; Vol. 12.
Liang 2010 {published data only}
    1. Liang J, Ahn M, Kang J, et al. First‐line treatment (txt) with pemetrexed‐cisplatin (PC), followed sequentially by gefitinib (G) or pemetrexed, in Asian, never‐smoker (n/smkr) patients (pts) with advanced NSCLC: An open‐label, randomized phase II trial. Journal of Clinical Oncology 2010;28(15 Suppl 1):Abstract 7591.
Nokihara 2006 {published data only}
    1. Nokihara H, Ohe Y, Kawaishi M, et al. A randomized phase II study of sequential carboplatin/paclitaxel (CP) and gefitinib (G) in chemotherapy‐naive patients with advanced non‐small‐cell lung cancer (NSCLC): Preliminary results. Journal of Clinical Oncology: ASCO Annual Meeting Proceedings 2006;24(18 Suppl):7096.
    1. Nokihara H, Ohe Y, Yamada K, et al. Randomized phase II study of sequential carboplatin/paclitaxel (CP) and gefitinib (G) in chemotherapy‐naive patients with advanced non‐small‐cell lung cancer (NSCLC): final results [abstract no. 8069]. Journal of Clinical Oncology: ASCO Annual Meeting Proceedings 2008;26(15 Suppl Pt I):441.
Puri 2013 {published data only}
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References to other published versions of this review

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