LAPS score for individualized treatment of advanced EGFR-mutated non-small cell lung cancer receiving EGFR-TKIs with or without bevacizumab

Figures & data

Table 1. Baseline clinical characteristics.

Characteristics		Total (n = 160)	T group (n = 107)	A + T group (n = 53)	P value
Age	≤ 65	93 (58.1%)	62 (57.9%)	31 (58.5%)	0.947
	> 65	67 (41.9%)	45 (42.1%)	22 (41.5%)
Gender	Female	87 (54.4%)	54 (50.5%)	33 (62.3%)	0.159
	Male	73 (45.6%)	53 (49.5%)	20 (37.7%)
Smoking history	No	91 (56.9%)	58 (54.2%)	33 (62.3%)	0.333
	Yes	69 (43.1%)	49 (45.8%)	20 (37.7%)
ECOG PS	0-1	140 (87.5%)	91 (85%)	49 (92.5%)	0.182
	2	20 (12.5%)	16 (15%)	4 (7.5%)
Clinical stage	IIIB-IVA	106 (66.2%)	71 (66.4%)	35 (66%)	0.968
	IVB	54 (33.8%)	36 (33.6%)	18 (34%)
Number of metastatic organs	< 2	124 (77.5%)	83 (77.6%)	41 (77.4%)	0.976
	≥ 2	36 (22.5%)	24 (22.4%)	12 (22.6%)
Brain metastasis	No	142 (88.8%)	95 (88.8%)	47 (88.7%)	0.984
	Yes	18 (11.2%)	12 (11.2%)	6 (11.3%)
Bone metastasis	No	96 (60.0%)	61 (57%)	35 (66%)
	Yes	64 (40.0%)	46 (43%)	18 (34%)
Liver metastasis	No	148 (92.5%)	99 (92.5%)	49 (92.5%)	1.000
	Yes	12 (7.5%)	8 (7.5%)	4 (7.5%)
EGFR mutation	19del	75 (46.9%)	48 (44.9%)	27 (50.9%)	0.615
	L858R	63 (39.4%)	45 (42.1%)	18 (34%)
	Others	22 (13.8%)	14 (13.1%)	8 (15.1%)
First-generation EGFR-TKI	Gefitinib	54 (33.8%)	40 (37.4%)	14 (26.4%)	0.167
	Icotinib	106 (66.2%)	67 (62.6%)	39 (73.6%)
Pre-treatment LAR	median (IQR)	5.6 (4.5, 6.8)	5.4 (4.5, 6.4)	6.2 (4.6, 7.7)	0.033

Figure 1. Clinical outcomes and efficacy analysis in EGFR-mutated advanced NSCLC with or without bevacizumab. Kaplan–Meier curves for PFS (A) and OS (B); best response (C), ORR (D) and DCR (E).

Figure 2. Kaplan–Meier curves of PFS (A) and OS (B) in EGFR-mutated advanced NSCLC receiving EGFR-TKI monotherapy according to ECOG PS. Kaplan–Meier curves of PFS (C) and OS (D) in EGFR-mutated advanced NSCLC receiving EGFR-TKIs monotherapy according to pre-treatment LAR.

Table 2. Univariate and Multivariate Cox analysis for PFS in advanced EGFR-mutated NSCLC receiving EGFR-TKI monotherapy.

Characteristics		Univariate analysis		Multivariate analysis
		HR (95% CI)	P value	HR (95% CI)	P value
Age	≤65	Reference
	>65	0.907 (0.598 − 1.373)	0.643
Gender	Female	Reference
	Male	0.939 (0.627 − 1.409)	0.762
Smoking history	No	Reference
	Yes	0.892 (0.594 − 1.341)	0.584
ECOG PS	0-1	Reference		Reference
	2	3.915 (2.190 − 7.001)	< 0.001	3.397 (1.854 − 6.224)	<0.001
Clinical stage	IIIB-IVA	Reference		Reference
	IVB	1.609 (1.047 − 2.472)	0.030	1.366 (0.871 − 2.142)	0.175
Number of metastatic organs	<2	Reference
	≥2	0.970 (0.596 − 1.580)	0.903
Brain metastasis	No	Reference
	Yes	1.629 (0.885 − 3.000)	0.117
Bone metastasis	No	Reference
	Yes	0.877 (0.582 − 1.320)	0.528
Liver metastasis	No	Reference
	Yes	1.741 (0.833 3.639)	0.141
EGFR mutation	19 Del	Reference		Reference
	L858R	1.029 (0.662 − 1.601)	0.898	0.895 (0.566 − 1.416)	0.636
	Others	2.471 (1.324 − 4.611)	0.004	1.830 (0.958 − 3.498)	0.067
First-generation EGFR-TKI	Gefitinib	Reference
	Icotinib	1.371 (0.898 − 2.093)	0.144
Pre-treatment LAR	Low	Reference		Reference
	High	1.730 (1.127 − 2.656)	0.012	1.559 (1.007 − 2.414)	0.047

Table 3. Univariate and multivariate analysis for OS in advanced EGFR-mutated NSCLC receiving EGFR-TKI monotherapy.

Characteristics		Univariate analysis		Multivariate analysis
		HR (95% CI)	P value	HR (95% CI)	P value
Age	≤65	Reference		Reference
	>65	1.561 (1.001 − 2.432)	0.049	0.982 (0.597 − 1.614)	0.942
Gender	Female	Reference
	Male	0.929 (0.595 − 1.452)	0.747
Smoking history	No	Reference
	Yes	0.907 (0.578 − 1.426)	0.673
ECOG PS	0-1	Reference		Reference
	2	17.355 (8.774 − 34.330)	<0.001	20.854 (9.507 − 45.746)	< 0.001
Clinical stage	IIIB-IVA	Reference		Reference
	IVB	1.486 (0.932 − 2.368)	0.096	0.974 (0.577 − 1.646)	0.922
Number of metastatic organs	<2	Reference
	≥2	1.307 (0.786 − 2.174)	0.302
Brain metastasis	No	Reference
	Yes	1.157 (0.594 − 2.255)	0.668
Bone metastasis	No	Reference
	Yes	0.908 (0.583 − 1.413)	0.669
Liver metastasis	No	Reference		Reference
	Yes	2.362 (1.123 − 4.968)	0.024	3.317 (1.409 − 7.806)	0.006
EGFR mutation	19 Del	Reference
	L858R	0.906 (0.568 − 1.446)	0.679
	Others	1.218 (0.587 − 2.525)	0.597
First-generation EGFR-TKI	Gefitinib	Reference
	Icotinib	1.231 (0.775 − 1.899)	0.397
Pre-treatment LAR	Low	Reference		Reference
	High	1.978 (1.249 − 3.133)	0.004	2.423 (1.485 − 3.955)	< 0.001

Figure 3. Time-dependent ROC curves of LAPS score for predicting 1-, 2-, 3-years OS (A) and P1-, 2-, 3-years PFS (B).

Figure 4. Clinical outcomes and efficacy analysis for EGFR-mutated advanced NSCLC receiving EGFR-TKI monotherapy in different risk groups. Kaplan–Meier curves for PFS (A) and OS (B); best response (C), ORR (D) and DCR (E).

Table 4. Efficacy response of different treatment modalities according to LAPS score.

Variables	Low risk (LAPS score = 0)			High risk (LAPS score = 1–2)
	T group (n = 40)	A + T group (n = 16)	P value	T group (n = 67)	A + T group (n = 37)	P value
Best response			0.573			0.012
PR	33 (82.5%)	13 (81.2%)		32 (47.8%)	25 (67.6%)
SD	5 (12.5%)	3 (18.8%)		22 (32.8%)	12 (32.4%)
PD	2 (5%)	0 (0%)		13 (19.4%)	0 (0%)
ORR	33 (82.5%)	13 (81.2%)	1.000	32 (47.8%)	25 (67.6%)	0.052
DCR	38 (95%)	16 (100%)	0.909	54 (80.6%)	37 (100%)	0.011

Figure 5. Kaplan-Meier curves of PFS (A) and OS (B) for patients who received EGFR-TKI with or without bevacizumab in low-risk groups. Kaplan–Meier curves of PFS (C) and OS (D) for patients who received EGFR-TKI with or without bevacizumab in high-risk groups.

Data availability statement

The data that support the findings of this study are available from the corresponding author upon reasonable request.