Table 1

Main characteristics of studies included in the meta-analysis

Reference	Location	No. of patients	Histology	Stage	Prior treatment	Current treatment	Gene	Mutation positive/total	End points	Response criteria	NOS score
Rotella 2014⁴⁹	Italy	88	ADC	IIIB or VI	Surgery or chemotherapy or radiotherapy	E: 150 mg/d	K-ras (exon 2)	13/88	ORR	RECIST	8
Kim 2014¹⁷	Korea	55	ADC	I-IV	Chemotherapy	E, G, PANHER	PIK3CA (exon 9, 20)	3/55	ORR, PFS, OS	RECIST	7
Kerner 2013⁴⁸	Netherlands	45	NSCLC	NR	NR	EGFR-TKI	K-ras (exon 2)	108/368	OS	RECIST	8
Fiala 2013⁴⁷	Czech Republic	179	SLC	IIIB or IV	Chemotherapy	G: 250 mg/d or E: 150 mg/d	K-ras (codon 12,13) PIK3CA (exon 9)	14/174 6/170	PFS, OS	NR	9
Campos-Parra 2013⁴⁶	Mexico	353	NSCLC	IIIB or IV	Chemotherapy	E or G	K-ras (codon 12, 13)	NR	PFS	RECIST	8
Murray 2012⁴⁵	Greece	30	NSCLC	IIIB or IV or recurrent	Chemotherapy	G: 250 mg/d or E: 150 mg/d	K-ras (codon 12, 13)	3/30	OS	RECIST	8
Metro 2014²⁴	Italy	67	NSCLC	IIIB or IV	Chemotherapy	E or G	K-ras (exon 2, 3)	18/67	ORR, PFS, OS	RECIST	9
Ludovini 2012¹⁸	Italy	166	NSCLC	III or IV	Chemotherapy	G: 250 mg/d or E: 150 mg/d	K-ras (exon 2, 3) PIK3CA (exon 9, 20)	11/162 6/145	ORR, OS	RECIST	9
Cadranel 2012⁴³	France	307	NSCLC	Advanced	Chemotherapy	E: 150 mg/d	K-ras (exon 2)	42/307	PFS, OS	WHO	9
Hirsch 2011⁴²	Multicenter	94	NSCLC	IIIB or IV	NR	E: 150 mg/d	K-ras (codon 12, 13)	20/94	ORR	RECIST	8
Zhu 2010⁴¹	China	17	NSCLC	IIIB or IV	NR	E: 150 mg/d	K-ras	3/17	ORR	RECIST	7
Tiseo 2010⁴⁰	Italy	63	NSCLC	III or IV	Chemotherapy	G: 250 mg/d	K-ras (exon 2)	7/63	ORR	RECIST	8
Douillard 2010³⁹	Multicenter	275	NSCLC	IIIB or IV	Chemotherapy	G: 250 mg/d	K-ras (codon 12, 13)	49/275	ORR	RECIST	9
Amann 2010⁸	USA	41	NSCLC	IIIB or IV or recurrent	Chemotherapy	E: 150 mg/d	K-ras (exon 2)	3/41	ORR, OS	RECIST	9
Varella-Garcia 2009³⁷	Japan	30	NSCLC	Recurrent	Surgery	G: 250 mg/d	K-ras (codon 12, 13)	4/30	ORR	RECIST	9
Marchetti 2009³⁶	Italy	83	ADC	IIIB or IV	Chemotherapy	G: 250 mg/d or E: 150 mg/d	K-ras (exon 2)	30/83	ORR, PFS, OS	WHO	8
Boldrini 2009³⁵	Italy	411	ADC	IV	Surgery	G: 250 mg/d or E: 150 mg/d	K-ras (codon 12, 13)	2/19	ORR	RECIST	7
Zucali 2008³⁴	Italy	49	NSCLC	III or IV	Chemotherapy or no	G: 250 mg/d	K-ras (exon 1, 2)	15/49	ORR	RECIST	8
Zhu 2008³³	Multicenter	206	NSCLC	IIIB or IV	Chemotherapy	E: 150 mg/d	K-ras (exon 2)	30/206	ORR	RECIST	9
Wu 2008³²	Taiwan	53	NSCLC	IB-IIIB	Surgery	E or G	K-ras (exon 1,2)	1/53	ORR	RECIST	8
Schneider 2008³¹	Germany	393	NSCLC	IIIB or IV	Chemotherapy or radiotherapy	E: 150 mg/d	K-ras (exon 2,3)	17/114	ORR, PFS, OS	RECIST	9
Miller 2008³⁰	USA	82	NSCLC	IIIB or IV	Chemotherapy or no	E: 150 mg/d	K-ras (exon 2)	18/80	ORR	RECIST	9
Felip 2008⁵⁵	Germany	39	NSCLC	Advanced	Chemotherapy or no	E: 150 mg/d	K-ras (exon 2,3)	7/39	ORR	RECIST	8
Zandwijk 2007²⁹	Netherlands	15	NSCLC	NR	Chemotherapy	G	K-ras (codon 2)	3/15	ORR	RECIST	8
Massarelli 2007⁵⁴	USA	70	NSCLC	IIIB or VI	Chemotherapy or no	G: 250 mg/d or E: 150 mg/d	K-ras (exon 1)	16/70	ORR	RECIST	9
Loprevite 2007⁵³	Italy	21	NSCLC	Advanced	Chemotherapy	G: 250 mg/d	K-ras (exon 2)	1/21	ORR	RECIST	8
Jackman 2007²⁸	USA	41	NSCLC	IIIB or IV	Surgery or Radiotherapy	E: 150 mg/d	K-ras (exon 2,3)	6/41	ORR	RECIST	9
Ichihara 2007²⁷	Japan	99	NSCLC	Advanced or recurrent	Surgery or chemotherapy	G: 250 mg/d	K-ras (exon 2)	8/87	ORR	WHO	8
Hirsch 2007⁵²	Multicenter	138	NSCLC	III or IV	Chemotherapy	G: 250 m g/d or E: 150 mg/d	K-ras (exon 2)	36/138	ORR	RECIST	9
Cappuzzo 2007²⁶	Italy	37	NSCLC	IIIB or IV	Chemotherapy or no	G: 250 mg/d	K-ras (exon 2)	1/37	ORR	RECIST	7
Hirsch 2006⁵¹	Multicenter	152	NSCLC	III or IV	Chemotherapy	G: 250 mg/d	K-ras (exon 2)	12/152	ORR	RECIST	9
Han 2006²⁵	Korea	69	NSCLC	IIIB or IV	NR	G:250 mg/d	K-ras (exon 2)	9/69	ORR	WHO	9
Giaccone 2006²⁴	Switzerland	53	NSCLC	IIIB or IV	Surgery or Radiotherapy	E: 150 mg/d	K-ras (exon 1, 2) PIK3CA (exon 9, 20)	10/25; 1/25	ORR	RECIST	9
Pao 2005⁵⁰	USA	59	ADC	NR	NR	G: 250 mg/d or E: 150 mg/d	K-ras (exon 2)	9/47	ORR	RECIST	7
Endoh 2006²³	Japan	78	NSCLC	Recurrent	Surgery or chemotherapy	G: 250 mg/d	K-ras (codon 12, 13, 61); PIK3CA (open reading frame)	7/78; 2/78	ORR, OS	RECIST	8

ADC: adenocarcinoma; SLC: squamous lung cancer; NSCLC: non-small cell lung cancer; NR: not reported; E: erlotinib; G: gefitinib; PANHER: PF00299804, an irreversible TKI of EGFR, HER2, and HER4; ORR: objective response rate; PFS: progression-free survival; OS: overall survival; No.: number of patients assessed; NOS: Newcastle-Ottawa scale