Sequential treatment of tyrosine kinase inhibitor and platinum-based doublet chemotherapy on EGFR mutant non-small cell lung cancer: a meta-analysis of randomized controlled clinical trials

Figures & data

Figure 1 Flowchart of publication selection process.

Table 1 Characteristics of the nine included clinical trials

Study	Year published	EGFR^+		Regimen		Medium OS (month)
		Race	Number of patients	First-line	Second-line
Inoue et al;^Citation13	2013; 2015	Asian	114	Taxol + P	Gefitinib	27.6
Miyauchi et al^Citation18			114	Gefitinib	PCT	28.9
Zhou et al^Citation14	2015	Asian	72	Gem + P	TKI	32
			82	Erlotinib	PCT	28
Wu et al^Citation7	2015	Asian	107	Gem + P	Erlotinib	24.7
			110	Erlotinib	Gem + P	29.4
Wu et al;^Citation9	2014; 2015	Asian	108	Gem + P	TKI	23.5
Yang et al^Citation11			216	Afatinib	PCT	23.1
Rosell et al;^Citation12	2012; 2014	Caucasian and Hispanic	88	PCT	TKI	16.5
Leon et al^Citation17			86	Erlotinib	PCT	22.9
Sequist et al;^Citation10	2013; 2015	Mixa	104	Pem + P	TKI	28.2
Yang et al^Citation11			203	Afatinib	PCT	28.2
Mitsudomi et al;^Citation8	2010; 2012	Asian	86	Doc + P	Gefitinib	38.8
Mitsudomi et al^Citation16			86	Gefitinib	PCT	35.5
Gridelli et al^Citation6	2012	Caucasian	20	Gem + P	Erlotinib	32.5
			19	Erlotinib	Gem + P	18.1
Fukuoka et al^Citation5	2011	Asian	129	Taxol + P	TKI	21.9
			132	Gefitinib	PCT	21.2

Notes: Miyauchi et al,¹⁸ Wu et al,⁹ Leon et al,¹⁷ Yang et al,¹¹ and Mitsudomi et al¹⁶ studies are the updated reports.

a Mix includes Asian, Caucasian, and Hispanic.

Abbreviations: Doc, docetaxel; Gem, gemcitabine; OS, overall survival; P, platinum; PCT, platinum-based doublet chemotherapy; Pem, pemetrexed; TKI, tyrosine kinase inhibitor.

Figure 2 Forest plot of OS comparing TKI-PCT arm and PCT-TKI arm.

Notes: TKI-PCT arm: patients treated with first-line TKI followed by second-line PCT; PCT-TKI arm: patients treated with first-line PCT followed by second-line TKI.
Abbreviations: CI, confidence interval; HR, hazard ratio; OS, overall survival; PCT, platinum-based doublet chemotherapy; TKI, tyrosine kinase inhibitor.

Figure 3 Egger’s publication bias plot.

InoueAKobayashiKMaemondoMUpdated overall survival results from a randomized phase III trial comparing gefitinib with carboplatin-paclitaxel for chemonaive non-small cell lung cancer with sensitive EGFR gene mutations (NEJ002)Ann Oncol2013241545922967997

 PubMed Web of Science ®Google Scholar

MiyauchiEInoueAKobayashiKEfficacy of chemotherapy after first-line gefitinib therapy in EGFR mutation-positive advanced non-small cell lung cancer-data from a randomized Phase III study comparing gefitinib with carboplatin plus paclitaxel (NEJ002)Jpn J Clin Oncol201545767067625877748

 PubMedGoogle Scholar

ZhouCWuYLChenGFinal overall survival results from a randomised, phase III study of erlotinib versus chemotherapy as first-line treatment of EGFR mutation-positive advanced non-small-cell lung cancer (OPTIMAL, CTONG-0802)Ann Oncol20152691877188326141208

 PubMed Web of Science ®Google Scholar

WuYLZhouCLiamCKFirst-line erlotinib versus gemcitabine/cisplatin in patients with advanced EGFR mutation-positive non-small-cell lung cancer: analyses from the phase III, randomized, open-label, ENSURE studyAnn Oncol20152691883188926105600

 PubMed Web of Science ®Google Scholar

WuYLZhouCHuCPAfatinib versus cisplatin plus gemcitabine for first-line treatment of Asian patients with advanced non-small-cell lung cancer harbouring EGFR mutations (LUX-Lung 6): an open-label, randomised phase 3 trialLancet Oncol201415221322224439929

 PubMed Web of Science ®Google Scholar

YangJCWuYLSchulerMAfatinib versus cisplatin-based chemotherapy for EGFR mutation-positive lung adenocarcinoma (LUX-Lung 3 and LUX-Lung 6): analysis of overall survival data from two randomised, phase 3 trialsLancet Oncol201516214115125589191

 PubMed Web of Science ®Google Scholar

RosellRCarcerenyEGervaisRErlotinib 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 trialLancet Oncol201213323924622285168

 PubMed Web of Science ®Google Scholar

LeonLFGolsorkhiALiuSDrozdowskyjARosellROverall survival analyses of first-line erlotinib versus chemotherapy in the EURTAC study population controlling for the use of post-study therapyAnn Oncol201425suppl 4iv426iv470

 Google Scholar

SequistLVYangJCYamamotoNPhase III study of afatinib or cisplatin plus pemetrexed in patients with metastatic lung adenocarcinoma with EGFR mutationsJ Clin Oncol201331273327333423816960

 PubMed Web of Science ®Google Scholar

MitsudomiTMoritaSYatabeYGefitinib 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 trialLancet Oncol201011212112820022809

 PubMed Web of Science ®Google Scholar

MitsudomiTMoritaSYatabeYUpdated overall survival results of WJTOG 3405, a randomized phase III trial comparing gefitinib (G) with cisplatin plus docetaxel (CD) as the first-line treatment for patients with non-small cell lung cancer harboring mutations of the epidermal growth factor receptor (EGFR)J Clin Oncol201230suppl abstr 7521

 Google Scholar

GridelliCCiardielloFGalloCFirst-line erlotinib followed by second-line cisplatin-gemcitabine chemotherapy in advanced non-small-cell lung cancer: the TORCH randomized trialJ Clin Oncol201230243002301122778317

 PubMed Web of Science ®Google Scholar

FukuokaMWuYLThongprasertSBiomarker 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 Oncol201129212866287421670455

 PubMed Web of Science ®Google Scholar