EGFR罕见突变非小细胞肺癌临床病理特征及疗效分析

doi:10.3877/cma.j.issn.1674-6902.2023.05.006

目的

分析非小细胞肺癌(non-small cell lung cancer, NSCLC)表皮生长因子受体(epidermal growth factor receptor, EGFR)罕见突变的临床病理特征及一线酪氨酸激酶抑制剂(tyrosine kinase inhibitor, TKI)治疗疗效。

方法

选择2017年8月至2023年7月我院收治的Ⅲb-Ⅳ期NSCLC罕见EGFR突变患者51例，分析临床病理特征，按治疗方法分为TKI治疗组42例、化疗组5例、姑息性治疗组4例，分析无进展生存期(progression-free survival, PFS)、总生存期(overall survival, OS)、客观缓解率(objective response rate, ORR)。

结果

51例罕见突变患者中20外显子插入(20ins)12例，主要罕见突变21例，复合突变18例。主要罕见突变L861Q 11例(22%)，罕见复合突变G719X＋S768I 8例(16%)。化疗组ORR为25%，低于靶向治疗组ORR 38.1%。TKI治疗对主要罕见突变(mPFS＝16个月，IQR 9~21；mOS＝19个月，IQR 14~28)和复合突变(mPFS＝15个月，IQR 8~20；mOS＝20个月，IQR 15~25)疗效较好。TKI治疗对20ins疗效较差(mPFS＝4个月，IQR 2~7；mOS＝6个月，IQR 3~7)。化疗对主要罕见突变和复合突变(mPFS＝6个月，IQR 1-12；mOS＝16个月，IQR 15-19)较TKI治疗好(P<0.001)。

结论

EGFR罕见突变对非小细胞肺癌一线治疗反应和生存期有重要影响。主要罕见突变和复合突变TKI治疗比化疗PFS和OS长。20 ins对TKI治疗反应差。

关键词: 非小细胞肺癌, 表皮生长因子受体罕见突变, 一线酪氨酸激酶抑制剂

Objective

To analyze the clinicopathological features of uncommon epidermal growth factor receptor (EGFR)mutations in non-small cell lung cancer(NSCLC) and the therapeutic efficacy of first-line tyrosine kinase inhibitors(TKI).

Methods

All of 51 patients with uncommon EGFR mutation in stage Ⅲb-Ⅳ NSCLC treated in our hospital from August 2017 to July 2023 were selected. The clinicopathological characteristics were analyzed. According to treatment methods, it was divided into TKI treatment group (42 cases), chemotherapy group (5 cases) and palliative treatment group (4 cases). Progression-free survival (PFS), overall survival (OS) and objective response rate (ORR) were analyzed.

Results

Among the 51 patients with uncommon mutations, 12 had 20 exon insertions (20 ins), 21 had major uncommon mutations, and 18 had complex mutations. There were 11 cases (22%) of uncommon mutation L861Q and 8 cases (16%) of uncommon complex mutation G719X+ S768I. The ORR of the chemotherapy group was 20%, lower than that of the targeted therapy group, which was 38.1%. TKI treatment for major uncommon mutations (mPFS=16 months, IQR 9-21; mOS=19 months, IQR 14-28) and complex mutations (mPFS=15 months, IQR 8-20; mOS=20 months, IQR 15~25) showed better efficacy. TKI treatment was less effective for 20 ins (mPFS=4 months, IQR 2-7; mOS=6 months, IQR 3~7). Chemotherapy for major uncommon mutations and complex mutations (mPFS=6 months, IQR 1-12; mOS=16 months, IQR 15-19) was better than TKI treatment(P<0.001).

Conclusion

Specific types of uncommon mutations in NSCLC patients with uncommon EGFR mutations have significant implications for treatment response and survival. Patients with major uncommon mutations and uncommon compound mutations demonstrated prolonged progression-free survival and overall survival when treated with TKIs, whereas patients with 20 exon insertions showed a suboptimal response to TKI treatment.

Key words: Non-small cell lung cancer, Uncommon epidermal growth factor receptor mutations, First-line tyrosine kinase inhibitor

表1 基本临床资料[n(%)]

临床特征	TKI治疗组(n＝42)	化疗组(n＝5)	姑息治疗组(n＝4)	P值
年龄(岁)	62(55，67)	61(53，61)	63(59，66)	0.500
性别				0.900
女	27(64)	3(60)	2(50)
男	15(36)	2(40)	2(50)
分期
Ⅲb	3(7.1)	1(20)	0(0)
Ⅳ	39(93)	4(80)	4(100)
吸烟
是	11(26)	1(20)	2(50)
否	31(74)	4(80)	2(50)
脑转移	13(31)	0(0)	2(50)	0.200
骨转移	22(52)	1(20)	1(25)	0.300
肝转移	9(21)	1(20)	1(25)	0.900
EGFR突变				0.003
20 ins	6(14)	2(40)	4(100)
主要罕见突变	19(45)	2(40)	0(0)
复合突变	17(40)	1(20)	0(0)
PS评分				0.005
0	24(57)	3(60)	1(25)
1	16(38)	1(20)	0(0)
2	2(4.8)	1(20)	3(75)

表1 基本临床资料[n(%)]

临床特征	TKI治疗组(n＝42)	化疗组(n＝5)	姑息治疗组(n＝4)	P值
年龄(岁)	62(55，67)	61(53，61)	63(59，66)	0.500
性别				0.900
女	27(64)	3(60)	2(50)
男	15(36)	2(40)	2(50)
分期
Ⅲb	3(7.1)	1(20)	0(0)
Ⅳ	39(93)	4(80)	4(100)
吸烟
是	11(26)	1(20)	2(50)
否	31(74)	4(80)	2(50)
脑转移	13(31)	0(0)	2(50)	0.200
骨转移	22(52)	1(20)	1(25)	0.300
肝转移	9(21)	1(20)	1(25)	0.900
EGFR突变				0.003
20 ins	6(14)	2(40)	4(100)
主要罕见突变	19(45)	2(40)	0(0)
复合突变	17(40)	1(20)	0(0)
PS评分				0.005
0	24(57)	3(60)	1(25)
1	16(38)	1(20)	0(0)
2	2(4.8)	1(20)	3(75)

图1 不同疗法患者PFS与OS比较

表2 不同EGFR突变TKI治疗疗效

EGFR突变	ORR	PFS	OS
20 ins	16.7	4个月(IQR 2~7)	6个月(IQR 3~7)
主要罕见突变	30.0	16个月(IQR 9~21)	19个月(IQR 14~28)
复合突变	52.9	15个月(IQR 8~20)	20个月(IQR 15~25)

表2 不同EGFR突变TKI治疗疗效

EGFR突变	ORR	PFS	OS
20 ins	16.7	4个月(IQR 2~7)	6个月(IQR 3~7)
主要罕见突变	30.0	16个月(IQR 9~21)	19个月(IQR 14~28)
复合突变	52.9	15个月(IQR 8~20)	20个月(IQR 15~25)

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Clinicopathological features and therapeutic efficacy of non-small cell lung cancer with uncommon EGFR mutation

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Clinicopathological features and therapeutic efficacy of non-small cell lung cancer with uncommon EGFR mutation