Efficacy and prognostic predictors of first-generation EGFR TKI-targeted therapy in patients with EGFR-mutated advanced non-small cell lung cancer

doi:10.19401/j.cnki.1007-3639.2022.07.006

Abstract

Abstract:

Background and purpose: Epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) treatment has become the first-line standard treatment for advanced non-small cell lung cancer (NSCLC) with EGFR mutation. However, 10%-30% of NSCLC patients with EGFR sensitive mutation still have primary drug resistance when receiving TKI targeted therapy. Therefore, to study the clinical efficacy of EGFR-TKI and find out its prognostic predictors has important significance for the treatment of advanced NSCLC patients with EGFR sensitive mutation. The purpose of this research was to evaluate the efficacy of icotinib as first-line treatment in patients with EGFR-mutant advanced NSCLC and investigate the prognostic predictors. Methods: A total of 258 stage ⅢB-Ⅳ NSCLC patients with EGFR mutation who were admitted to Fujian Cancer Hospital from January 2016 to November 2017 were selected. One hundred and eighteen advanced NSCLC patients with EGFR mutation were enrolled, and baseline circulating tumor DNA (ctDNA) EGFR-mutant status was determined using the plasma test. All these patients received icotinib 125mg three times a day. The χ² test was used to compare the differences in clinicopathological characteristics between different EGFR mutation groups. Progression-free survival (PFS) and overall survival (OS) were estimated by the Kaplan-Meier survival curve. The log-rank test was used for univariate analysis, and the COX regression model was used for multivariate analysis. Results: The objective response rate (ORR) of 118 patients was 62.7% (95% CI: 53.9%-71.6%), the disease control rate (DCR) was 92.4% (95% CI: 87.5%-97.2%), and the median PFS was 11.3months (95% CI: 9.1-13.5 months), and the median OS was 32.0 months (95% CI: 26.9-37.1 months). No statistically significant difference was found in the clinicopathological characteristics between different EGFR expression types (P>0.05), while the best efficacy between different EGFR mutation groups was significantly different (P=0.040). Univariate analysis showed that EGFR mutation status in plasma ctDNA test was not correlated with PFS and OS of patients (P>0.05). Multivariate analysis showed that baseline lactate dehydrogenase (LDH) expression level, EGFR types, pleural effusion and the best curative effect might be independent factors of PFS. The patient’s N stage, bone metastasis, time to PFS and presence of EGFR T790M mutation might be independent predictors of OS. Conclusion: Icotinib as first-line treatment was effective in EGFR-mutant advanced NSCLC patients. The EGFR mutation status in plasma ctDNA test was not correlated with the clinical efficacy of patients. Bone metastasis was found to be an independent factor of worse prognosis.

Key words: Non-small cell lung cancer, Epidermal growth factor, Overall survival, Circulating tumor DNA, Bone metastasis

CLC Number:

R734.2

HONG Yaping, HUANG Yunjian, HUANG Zhangzhou, CHEN Shengjia, ZHONG Qiaofeng, ZENG Hongfu, ZHUANG Wu. Efficacy and prognostic predictors of first-generation EGFR TKI-targeted therapy in patients with EGFR-mutated advanced non-small cell lung cancer[J]. China Oncology, 2022, 32(7): 624-634.

Figures/Tables 8

Tab. 1

Tab. 2

Tab. 3

Univariate analysis of the correlation between clinical characteristics and PFS/OS in advanced NSCLC patients with EGFR mutation"

Item	mPFS/month	95% CI	P value	mOS/month	95% CI	P value
Gender			0.660			0.360
Male	11.5	8.0-15.0		30.5	23.7-37.4
Female	11.3	9.0-13.6		33.8	24.1-43.6
Age/year			0.204			0.266
≥60	12.2	10.1-14.4		30.5	17.7-43.4
<60	10.1	7.5-12.7		35.2	26.6-43.8
Smoking history			0.258			0.206
Yes	14.1	11.3-16.8		43.4	26.9-59.8
No	10.7	8.4-13.0		30.7	25.0-36.4
Adenocarcinoma			0.956			0.262
Yes	11.4	9.5-13.4		34.0	29.7-38.3
No	8.4	5.6-11.1		20.4	4.6-36.2
Overall stage			0.115			0.656
ⅢB-ⅢC	13.3	6.9-19.6		-	-
Ⅳa	12.6	10.4-14.8		34.0	27.4-40.6
Ⅳb	9.0	8.0-10.0		30.5	21.4-39.6
Postoperative recurrence			0.008			0.070
Yes	20.9	15.4-26.5		36.5	-
No	9.1	7.5-10.7		29.9	19.5-40.2
T stage			0.035			0.002
T₁	13.2	0.543-25.8		41.9	-
T₂	8.3	4.7-11.8		30.7	22.3-39.1
T₃	4.6	2.9-6.3		7.8	3.2-12.3
T₄	11.4	9.7-13.1		34.0	28.3-39.7
N stage			0.100			0.013
N₀	14.0	9.1-18.9		41.9	19.9-64.1
N₁	16.9	4.1-29.6		33.7	18.5-48.9
N₂	9.1	4.1-14.0		29.9	8.6-51.1
N₃	8.6	5.0-12.1		18.1	7.7-28.4
M stage			0.365			0.181
M₀	13.3	8.0-18.6		-	-
M_1a	12.2	10.4-14.0		37.0	32.5-41.4
M_1b	12.3	1.8-22.8		13.5	0.7-30.5
M_1c	9.0	7.7-10.3		30.5	21.4-39.7
Pleural effusion			0.018			0.487
Yes	9.3	5.0-13.7		29.9	25.8-34.0
No	12.1	8.8-15.3		35.1	25.8-37.0
Intrapulmonary metastasis			0.806			0.851
Yes	10.2	6.8-13.6		33.8	28.0-40.0
No	11.4	8.8-13.9		30.8	22.5-39.1
Bone metastasis			0.050			0.020
Yes	8.8	7.2-10.5		13.7	2.8-22.5
No	11.4	9.4-13.5		35.1	29.6-40.6
Brain metastasis			0.679			0.841
Yes	9.1	5.8-12.4		30.8	23.3-38.3
No	11.5	9.3-13.7		32.0	25.8-38.3
Liver metastasis			0.074			0.064
Yes	4.1	0.3-8.0		8.0	0.0-17.2
No	11.4	8.5-14.2		34.0	29.1-38.9
Adrenal metastasis			0.455			0.247
Yes	16.9	4.8-28.9		-	-
No	10.2	7.3-13.1		33.7	28.6-38.8
Carcinomatous lymphangitis			0.008			0.097
Yes	4.1	1.8-8.6		8.0	1.0-22.1
No	11.5	9.1-13.9		33.8	29.4-38.3
EGFR detected by tissue			0.201			0.032
19DEL	11.5	9.7-13.3		35.1	30.1-40.1
L858R	8.6	6.4-10.7		23.3	13.5-33.1
Rare mutation	11.4	5.4-17.5		38.6	19.8-57.4
EGFR detected by tissue			0.027			0.015
19DEL	11.5	9.7-13.3		36.5	31.4-41.6
L858R	8.6	6.4-10.7		23.3	12.8-33.8
EGFR detected by blood			0.407			0.574
Positive	11.4	9.3-13.5		35.1	27.7-42.5
Negative	10.2	7.2-13.2		29.4	24.8-33.9
Best curative effect			0.000			0.001
PR	12.1	10.5-13.7		36.5	32.2-40.8
SD	10.8	6.8-14.7		28.5	17.0-40.1
PD	1.0	0.5-1.5		7.8	3.6-12.0
Baseline LDH			0.000			0.011
Normal	11.4	8.4-14.3		34.0	28.4-39.6
Elevated	4.9	3.7-6.2		12.0	4.9-19.1
T790M						0.002
Yes				36.5	31.7-41.3
No				8.3	4.6-12.1

Tab. 3

Tab. 4

Fig. 1

Tab. 5

Fig. 2

Tab. 6

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Item	PFS			OS
Item	B	HR (95% CI)	P value	B	HR (95% CI)	P value
Age/age	-0.018	0.982 (0.964-1.001)	0.060	-0.005	0.995 (0.975-1.015)	0.627
LDH	0.001	1.001 (1.000-1.002)	0.004	0.000	1.001 (1.000-1.002)	0.001
Long diameter of primary lesion	0.166	1.181 (1.037-1.345)	0.012	0.144	1.155 (1.013-1.317)	0.031
Sum of long diameters of target lesions	0.013	1.047 (1.021-1.073)	0.000	0.044	1.045 (0.985-1.107)	0.143
Sum of area of target lesions	0.016	1.016 (1.002-1.030)	0.026	0.008	1.008 (0.995-1.020)	0.231
PFS				-0.101	0.904 (0.864-0.945)	0.000

Item	HR (95% CI)	P value
Baseline LDH	2.788 (1.239-6.270)	0.013
Bone metastasis	0.324 (0.316-1.464)	0.324
EGFR type	2.318 (1.037-5.181)	0.040
Pleural effusion	2.604 (1.072-6.329)	0.035
Carcinomatous lymphangitis	1.219 (0.348-4.262)	0.757
long diameter of primary lesion	1.021 (0.792-1.316)	0.874
Best curative effect	2.513 (1.365-4.625)	0.003

Item	HR (95% CI)	P value
T stage	0.571 (0.296-1.103)	0.095
N stage	3.595 (1.287-10.041)	0.015
Bone metastasis	13.106 (2.095-81.995)	0.006
Baseline LDH	0.381 (0.074-1.957)	0.248
PFS	0.866 (0.754-0.995)	0.042
EGFR type	1.207 (0.273-5.338)	0.804
T790M	0.150 (0.023-0.995)	0.049