Erlotinib usage after prior treatment with gefitinib in advanced non-small cell lung cancer: A clinical perspective and review of published literature

Table 1 Baseline characteristics of subjects in studies evaluating response to erlotinib after gefitinib

Ref.	Year	Country	Type of study	No. of patients	Gender (M/F)	Smoking status (smokers/NS)	Histology (A/S/other)
Garfield[9]	2005	United States	Case report	1	1/0	1/0	0/0/1
Viswanathan et al[16]	2005	United States	Case report	5	1/4	2/3	NA
Walther et al[17]	2006	United Kingdom	Case report	1	0/1	0/1	1/0/0
Chang et al[18]	2007	Taiwan	Case report	1	1/0	1/0	1/0/0
Cho et al[19]	2007	South Korea	Prospective	21	10/11	10/11	16/3/2
Gridelli et al[32]	2007	Italy	Case report	3	0/3	0/3	3/0/0
Kim et al[33]	2007	South Korea	Case report	1	0/1	0/1	1/0/0
Costa et al[23]	2008	United States	Retrospective	18	7/11	7/11	16/0/2
Lee et al[21]	2008	South Korea	Prospective	23	4/19	0/23	22/0/1
Vasile et al[22]	2008	Italy	Prospective	8	4/4	1/7	6/0/2
Wong et al[20]	2008	Singapore	Retrospective	14	4/10	1/13	10/1/3
Wong et al[34]	2008	Singapore	Case report	1	0/1	0/1	1/0/0
Wu et al[35]	2008	Taiwan	Case report	1	0/1	0/1	1/0/0
Katayama et al[36]	2009	Japan	Retrospective	7	2/5	NA	7/0/0
Sim et al[24]	2009	South Korea	Retrospective	16	0/16	0/16	16/0/0
Zhou et al[25]	2009	China	Prospective	21	14/7	10/11	8/9/4
Wong et al[26]	2010	China	Retrospective	21	2/19	1/20	19/0/2
Asami et al[27]	2011	Japan	Retrospective	42	13/29	14/28	42/0/0
Hata et al[29]	2011	Japan	Retrospective	125	49/76	55/70	117/NA/8
Masuda et al[37]	2011	Japan	Case report	3	3/0	NA	3/0/0
Shoji et al[38]	2011	Japan	Case report	1	1/0	NA	1/0/0
Song et al[39]	2011	China	Retrospective	20	9/11	5/15	18/0/2
Takenaka et al[40]	2011	Japan	Case report	1	0/1	0/1	1/0/0
Saito et al[41]	2012	Japan	Retrospective	21	9/12	9/12	19/0/2
Tetsumoto et al[42]	2012	Japan	Case report	2	0/2	0/2	2/0/0
Koyama et al[43]	2013	Japan	Retrospective	1041	56/48	50/54	90/6/8

¹Of the 104 patients, only 54 had prior treatment with gefitinib. A: Adenocarcinoma; S: Squamous cell carcinoma; M: Male; F: Female; NA: Not available; smokers: Includes current and ex smokers; NS: Non-smokers.

Table 2 Prevalence of epidermal growth factor receptor mutations and comparison of responses to gefitinib and erlotinib n (%)

Ref.	No. ofpatients	EGFRmutations no	E19 Del/E21L858R	Response to prior gefitinib				Response to erlotinib
				CR	PR	SD	PD	CR	PR	SD	PD
Garfield[9]	1	NA	NA				1(100)		1(100)
Viswanathan et al[16]	5	NA	NA		4(80.0)		1(20.0)				5(100)
Walther et al[17]	1	NA	NA				1(100)		1(100)
Chang et al[18]	1	1 (100)	1/0		1(100)				1(100)
Cho et al[19]	21	5 (23.8)	5/0		6(28.6)	4(19.0)	11(52.4)		2(9.5)	4(19.0)	15(71.5)
Gridelli et al[32]	3	NA	NA			3(100)			1(33.3)	2(66.7)
Kim et al[33]	1	NA	NA		1(100)				1(100)
Costa et al[23]	181	17 (94.4)	4/13		11(84.6)	2(15.4)			1(7.7)	2(15.4)	10(76.9)
Lee et al[21]	23	3 (13.0)	3/0		15(65.2)	2(8.7)	6(26.1)		1(4.3)	1(4.3)	21(91.4)
Vasile et al[22]	8	NA	NA		4(50.0)	4(50.0)			2(25.0)	3(37.5)	3(37.5)
Wong et al[20]	14	7 (50.0)	4/3		9(64.3)		5(35.7)			5(35.7)	9(64.3)
Wong et al[34]	1	1 (100)	1/0		1(100)					1(100)
Wu et al[35]	1	1 (100)	0/1		1(100)					1(100)
Katayama et al[36]	7	6 (85.7)	4/2	2(28.6)	2(28.6)	3(42.8)			3(42.9)	3(42.9)	1(14.3)
Sim et al[24]	16	5 (31.3)	2/3		9(56.3)	2(12.5)	5(31.2)		1(6.3)	3(18.7)	12(75.0)
Zhou et al[25]	21	7 (33.3)	NA/NA	2(9.5)		8(38.1)	11(52.4)		2(9.5)	4(19.1)	15(71.4)
Wong et al[26]	21	3 (14.3)	0/3		18(85.7)		3(14.3)		12(57.1)		9(42.9)
Asami et al[27]	42	28 (66.7)	14/14		22(52.4)	17(40.5)	3(7.1)		1(2.4)	24(57.1)	17(40.5)
Hata et al[29]	1252	63 (50.4)	NA/NA	3(2.5)	68(56.2)	22(18.2)	28(23.1)		11(8.8)	44(35.2)	70(56.0)
Masuda et al[37]	3	3 (100)	2/1		3(100)				3(100)
Shoji et al[38]	1	0 (0)	0 (0)				1(100)		1(100)
Song et al[39]	20	5 (25.0)	3/2		5(25.0)	9(45.0)	6(30.0)			7(35.0)	13(65.0)
Takenaka et al[40]	1	1 (100)	1/0			1(100)			1(100)
Saito et al[41]	21	12 (57.1)	0/12		16(76.2)	5(23.8)			2(9)	6(19)	13(62)
Tetsumoto et al[42]	2	2 (100)	1/1		2(100)				2(100)
Koyama et al[43]	54	44 (81.5)	22/22	4(7.4)	32(59.3)	13(24.0)	5(9.3)	0 (0)	4(7.4)	30(55.6)	20(37.0)

¹Response to gefitinib and erlotinib was evaluable for 13 patients only;

²Response to gefitinib was evaluable for 121 patients only. EGFR: Epidermal growth factor receptor; PR: Partial response; CR: Complete response; PD: Progressive disease; SD: Stable disease; E19: Exon 19; E21: Exon 21; Del: Deletion; NA: Not available.

Table 3 Response rates and survival rates with erlotinib following gefitinib therapy

Ref.	RR	DCR	PFS	OS
Cho et al[19]	9.50%	28.60%	60 d	158 d
Costa et al[23]			2 mo
Lee et al[21]	4.30%	8.70%
Vasile et al[22]	25%	62.50%	5.9 mo	14.6 mo
Wong et al[20]		35.70%	97 d
Sim et al[24]		25%	1.7 mo
Zhou et al[25]	9.50%	28.50%	55 d	135 d
Wong et al[26]		57.10%	14.9 wk	40 mo
Asami et al[27]	2.40%	59.50%	3.4 mo	7.1 mo
Hata et al[29]	9%	44%	2 mo	11.8 mo
Song et al[39]	0	35%	31 d	4.2 mo
Saito et al[41]		38.10%		369 d
Koyama et al[43]	7.40%	63.00%	135 d	333 d

RR: Response rate; DCR: Disease control rate; PFS: Progression free survival: OS: Overall survival.

Table 4 Pooled analysis of demographic profile, prevalence of epidermal growth factor receptor mutations and disease control rates with erlotinib following prior gefitinib therapy

Female gender : 60.6% (292 of 482)

Adenocarcinoma histology: 88.3% (421 of 477)

Non smokers: 64.5% (304 of 471)

East Asian ethnicity: 92.3% (445 of 482)

EGFR mutation positive status1: 48.4% (224 of 463)

Disease control rate with prior gefitinib treatment: 79.4% (336 of 423)

Disease control rate with subsequent erlotinib treatment: 45.4% (194 of 427)

¹Indicates presence of sensitizing EGFR mutations (exon 19 deletion or exon 21 L858R mutation). EGFR: Epidermal growth factor receptor.

Table 5 Potential factors predicting response to erlotinib following prior gefitinib therapy

Previous response to gefitinib (most important)

Longer duration of response to prior gefitinib

Female gender

Adenocarcinoma histology

Non smokers

East Asian ethnicity

EGFR mutation positive status1

Good performance status

Chemotherapy cycles in between gefitinib and erlotinib

¹Indicates presence of sensitizing EGFR mutations (exon 19 deletion or exon 21 L858R mutation). EGFR: Epidermal growth factor receptor.