ALK and ROS1 concurrent with EGFR mutation in patients with lung adenocarcinoma

Figures & data

Table 1 Characteristics of the study population and comparison (n=421)

Characteristics	Total	Single EGFR mutation (n=408)	Concurrent gene (n=13)	P-value
Gender				0.37
Male	245	239	6
Female	176	169	7
Age, years				0.04
<60	224	213	11
≥60	197	195	2
Smoking status				0.20
Never	305	295	12
Former/current	116	113	1
Stage at EGFR-TKI treatment				0.83
IIIB	12	12	0
IV	409	396	13
EGFR mutation type				0.67
Exon 19 deletion + exon 21 L858R	386	374	12
Other types	35	34	1
Performance score at EGFR-TKI treatment				0.70
0–1	356	345	11
2–3	65	63	2

Abbreviation: TKI, tyrosine kinase inhibitor.

Table 2 Clinical characteristics of 13 patients with EGFR and ALK/ROS1 concurrent genes

Case	Gender	Age (years)	Smoking history	EGFR type	EGFR-TKI PFS	Response	ALK/ROS1	Crizotinib PFS	Response	Post-TKI treatment	Response	OS/month
1	Female	47	No	19del	6.6	PR	EML4–ALK	–	–	Chemotherapy	SD	23.0
2	Male	55	No	G719X	2.0	PD	EML4–ALK	11.2	PR	Supportive care	–	21.0
3	Female	57	No	19del	3.1	SD	EML4–ALK	6.0	PR	Supportive care	–	11.5
4	Male	59	No	L858R	4.0	SD	EML4–ALK	5.0	SD	Chemotherapy	PR	45.0
5	Female	65	No	19del	17.5	PR	EML4–ALK	–	–	Supportive care	–	23.5
6	Female	62	No	L858R	12.0	PR	EML4–ALK	–	–	Chemotherapy	PD	33.2
7	Male	56	Yes	19del	10.2	PR	EML4–ALK	–	–	Supportive care	–	24.0
8	Female	55	No	19del	1.1	PD	CD74–ROS1	7.0	SD	Chemotherapy	PD	15.4
9	Male	45	No	19del	2.0	PD	EZR–ROS1	23.0	PR	Chemotherapy	PD	35.0
10	Female	49	No	L858R	1.3	PD	EML4–ALK	–	–	Supportive care	–	17.6
11	Female	38	No	19del	9.0	PR	EML4–ALK	1.2	PD	Chemotherapy	SD	21.5
12	Male	59	No	L858R	7.6	PR	CD74–ROS1	2.0	PD	Chemotherapy	PD	24
13	Male	51	No	19del	8.2	SD	EML4–ALK	7.5	PR	Chemotherapy	SD	48+

Abbreviations: TKI, tyrosine kinase inhibitor; PFS, progression-free survival; OS, overall survival; PR, partial response; SD, stable disease; PD, progressive disease.

Table 3 Clinical efficacy comparison of EGFR-TKI in single EGFR mutation and concurrent gene alterations

Best response	Single EGFR mutation (n=408)	Concurrent gene (n=13)	P-value
CR, n (%)	2 (0.5)	0 (0.0)	–
PR, n (%)	249 (61.0)	6 (46.2)	–
SD, n (%)	87 (21.3)	3 (23.1)	–
PD, n (%)	70 (17.2)	4 (30.8)	–
ORR (%)	61.5	46.2	0.26
DCR (%)	82.8	69.2	0.37
Median PFS	10.7	6.6	0.004
Median OS	21.0	23.0	0.196

Abbreviations: TKI, tyrosine kinase inhibitor; CR, complete response; PR, partial response; SD, stable disease; PD, progressive disease; ORR, objective response rate; DCR, disease control rate; PFS, progression-free survival; OS, overall survival.

Figure 1 Comparison of PFS between single EGFR and concomitant ALK/ROS1 gene mutants on EGFR-TKI (10.7 vs 6.6 months, P=0.004).

Abbreviations: PFS, progression-free survival; TKI, tyrosine kinase inhibitor.

Figure 2 Comparison of OS between single EGFR and concomitant ALK/ROS1 gene mutants on EGFR-TKIs (21.0 vs 23.0 months, P=0.196).

Abbreviations: OS, overall survival; TKI, tyrosine kinase inhibitor.

Table S1 The subtypes of EGFR/ALK/ROS1 genes

Gene type	Subtype of gene
ALK fusion	EML4 exon 13; ALK exon 20
	EML4 exon 6 ins 33; ALK exon 20
	EML4 exon 20; ALK exon 20
	EML4 exon 18; ALK exon 20
	EML4 exon 2; ALK exon 20
ROS1 fusion	SLC34A2 exon 4; ROS1 exon 32
	SLC34A2 exon 14 del; ROS1 exon 32
	CD74 exon 6; ROS1 exon 32
	SDC4 exon 2; ROS1 exon 32
	SDC4 exon 4; ROS1 exon 32
	SLC34A2 exon 4; ROS1 exon 34
	SLC34A2 exon 14 del; ROS1 exon 34
	CD74 exon 6; ROS1 exon 34
	SDC4 exon 4; ROS1 exon 34
	EZR exon 10; ROS1 exon 34
	TPM3 exon 8; ROS1 exon 35
	LRIG3 exon 16; ROS1 exon 35
	GOPC exon 8; ROS1 exon 35
	E746_A750del (1)
	E746_A750del (2)
	L747_P753>S
	E746_T751>I
	E746_T751del
	E746_S752>V
	L747_T751>Q
	L747_E749del
	L747_S752del
	L747_A750>P
EGFR mutation	L747_P753>Q
	L747_T751del
	L747_T751>P
	S768I
	L858R
	G719A
	G719C
	G719S
	T790M
	L861Q
	H773_V774insH
	D770_N771insG
	V769_D770insASV