不同剂量贝伐珠单抗联合培美曲塞及铂类药物治疗晚期NSCLC疗效与安全性倾向性匹配分析

doi:10.3877/cma.j.issn.1674-6902.2026.04.008

中华肺部疾病杂志(电子版) ›› 2026, Vol. 19 ›› Issue (04) : 578 -585. doi: 10.3877/cma.j.issn.1674-6902.2026.04.008

论著

不同剂量贝伐珠单抗联合培美曲塞及铂类药物治疗晚期NSCLC疗效与安全性倾向性匹配分析

李洋¹, 陈雨欣¹^,^†(

), 高娜², 李继霞¹, 米晶晶¹, 贺元¹, 曹鸿鑫³

¹719000　榆林，西安交通大学第一附属医院榆林医院药学部
²719000　榆林，西安交通大学第一附属医院榆林医院呼吸内科
³719000　榆林，西安交通大学第一附属医院榆林医院肿瘤科

收稿日期:2026-04-13 出版日期:2026-08-25
通信作者: 陈雨欣
基金资助:
陕西省药学会医院药学高质量发展项目(XM-2024-1-2-20)

Propensity score matched analysis of the efficacy and safety of different doses of bevacizumab combined with pemetrexed and platinum-based drugs in the treatment of advanced NSCLC

Yang Li¹, Yuxin Chen¹^,^†(), Na Gao², Jixia Li¹, Jingjing Mi¹, Yuan He¹, Hongxin Cao³

¹Department of Pharmacy, Yulin Hospital, The First Affiliated Hospital of Xi′an Jiaotong University, Yulin 719000, China
²Department of Respiratory Medicine, Yulin Hospital, The First Affiliated Hospital of Xi′an Jiaotong University, Yulin 719000, China
³Department of Oncology, Yulin Hospital, The First Affiliated Hospital of Xi′an Jiaotong University, Yulin 719000, China

Received:2026-04-13 Published:2026-08-25
Corresponding author: Yuxin Chen

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引用本文：

李洋, 陈雨欣, 高娜, 李继霞, 米晶晶, 贺元, 曹鸿鑫. 不同剂量贝伐珠单抗联合培美曲塞及铂类药物治疗晚期NSCLC疗效与安全性倾向性匹配分析[J/OL]. 中华肺部疾病杂志(电子版), 2026, 19(04): 578-585.

Yang Li, Yuxin Chen, Na Gao, Jixia Li, Jingjing Mi, Yuan He, Hongxin Cao. Propensity score matched analysis of the efficacy and safety of different doses of bevacizumab combined with pemetrexed and platinum-based drugs in the treatment of advanced NSCLC[J/OL]. Chinese Journal of Lung Diseases(Electronic Edition), 2026, 19(04): 578-585.

目的

探讨不同剂量贝伐珠单抗联合培美曲塞及铂类药物一线治疗晚期非鳞状非小细胞肺癌(non-small cell lung cancer, NSCLC)的疗效与安全性。

方法

选择2021年9月至2025年12月我院收治的接受贝伐珠单抗联合培美曲塞和铂类方案治疗的76例晚期非鳞状NSCLC患者资料，其中低剂量组(7.5 mg/kg)45例，高剂量组(15 mg/kg)31例。采用倾向评分匹配(propensity score matching, PSM)1︰1分为每组28例。比较两组客观缓解率(objective response rate, ORR)、疾病控制率(disease control rate, DCR)、总生存期(overall survival, OS)及不良反应；Kaplan Meier法绘制生存曲线，Log-rank检验比较生存差异，Cox回归进行亚组分析。

结果

PSM后两组基线特征均衡(P>0.05)。低剂量组较高剂量组ORR[53.57% 比35.71%](P＝0.179)，DCR[78.57% 比60.71%](P＝0.146)。中位OS低剂量组较高剂量组[24.5个月(95%CI：19.324~29.676)比22.8个月(95%CI：17.512~28.088)]，(HR＝1.167，95%CI：0.540~2.519，Log-rank P＝0.695)。亚组分析显示，基线特征年龄、性别、东部肿瘤协作组体能状态(Eastern Cooperative Oncology Group Performance Status, ECOG-PS)、吸烟史、病理亚型、高血压、慢性阻塞性肺疾病(chronic obstructive pulmonary disease, COPD)、KRAS突变等与剂量疗效间无显著交互作用(P>0.05)。两组不良反应以1~2级为主；≥3级严重血液学及非血液学毒性发生率组间差异无统计学意义(P>0.05)，低剂量组1~2级恶心/呕吐发生率高于高剂量组(42.86%比17.86%，P＝0.042)，未增加≥3级胃肠道毒性(7.14% 比3.57%，P＝0.553)。

结论

7.5 mg/kg低剂量贝伐珠单抗联合培美曲塞＋铂类一线治疗晚期非鳞状NSCLC的疗效不劣于15 mg/kg标准剂量，不良反应风险相近，安全性好。

关键词: 非小细胞肺癌, 贝伐珠单抗, 培美曲塞, 铂类, 倾向性评分匹配, 生存分析

Objective

To investigate the efficacy and safety of different doses of bevacizumab combined with pemetrexed and platinum-based chemotherapy as first-line treatment for advanced non-squamous non-small cell lung cancer (NSCLC).

Methods

Data from 76 patients with advanced non-squamous NSCLC treated with bevacizumab combined with pemetrexed and platinum-based regimens admitted to our hospital between September 2021 and December 2025 were selected. Among them, 45 patients received the low-dose group (7.5 mg/kg) and 31 patients received the high-dose group (15 mg/kg). Propensity score matching (PSM) was used to randomly assign 28 patients to each group at a 1︰1 ratio. Objective response rate (ORR), disease control rate (DCR), overall survival (OS), and adverse reactions were compared between the two groups. Survival curves were plotted using the Kaplan-Meier method, and survival differences were compared using the Log-rank test. Cox regression was used for subgroup analysis.

Results

Baseline characteristics were balanced between the two groups after PSM (P>0.05). ORR was 53.57% vs. 35.71% in the low-dose group (P=0.179), and DCR was 78.57% vs. 60.71% (P=0.146) in the high-dose group. Median OS was 24.5 months (95%CI: 19.324~29.676) vs. 22.8 months (95%CI: 17.512~28.088) in the low-dose group (HR=1.167, 95%CI: 0.540~2.519, Log-rank P=0.695). Subgroup analysis showed no significant interaction between baseline characteristics such as age, sex, Eastern Cooperative Oncology Group Performance Status (ECOG PS), smoking history, pathological subtype, hypertension, chronic obstructive pulmonary disease (COPD), and KRAS mutation and dose-response relationship (P>0.05). Adverse reactions were predominantly grade 1~2 in both groups; there was no statistically significant difference in the incidence of grade ≥3 serious hematologic and non-hematologic toxicities between the groups (P>0.05). The incidence of grade 1~2 nausea/vomiting was higher in the low-dose group than in the high-dose group (42.86% vs. 17.86%, P=0.042), but no increase in grade ≥3 gastrointestinal toxicities (7.14% vs. 3.57%, P=0.553).

Conclusion

The efficacy of low-dose bevacizumab (7.5 mg/kg) combined with pemetrexed and platinum-based chemotherapy as first-line treatment for advanced non-squamous NSCLC is non-inferior to the standard dose (15 mg/kg), with similar adverse reaction risks and good safety profile.

Key words: Non-small cell lung cancer, Bevacizumab, Pemetrexed, Platinum, Propensity score matching, Survival analysis

表1 两组患者PSM前和PSM后临床资料比较

临床资料	PSM前				PSM后
临床资料	低剂量组(n＝45)	高剂量组(n＝31)	t/χ²值	P值	低剂量组(n＝28)	高剂量组(n＝28)	t/χ²值	P值
男性[n(%)]	26(57.78)	25(80.65)	4.348	0.037	22(78.57)	21(75.00)	0.100	0.752
年龄[岁，(±s)]	67.42±9.54	64.05±6.57	－1.824	0.072	65.93±8.14	65.23±6.38	－0.358	0.722
吸烟状态[n(%)]			0.150	0.699			0.220	0.639
既往或当前吸烟	41(91.11)	29(93.55)			25(89.29)	26(92.86)
从不吸烟	4(8.89)	2(6.45)			3(10.71)	2(7.14)
吸烟指数[n(%)]			0.712	0.399			0.100	0.752
<20包年	8(17.78)	8(25.81)			6(21.43)	7(25.00)
≥20包年	37(82.22)	23(74.19)			22(78.57)	21(75.00)
ECOG PS评分[n(%)]			0.676	0.411			0.080	0.778
0分	12(26.67)	11(35.48)			9(32.14)	10(35.71)
1分	33(73.33)	20(64.52)			19(67.86)	18(64.29)
合并症[n(%)]
高血压	16(35.56)	11(35.48)	0.000	0.995	9(32.14)	9(32.14)	0.000	1.000
糖尿病	7(15.56)	8(25.81)	1.218	0.270	2(7.14)	7(25.00)	3.310	0.069
COPD	16(35.56)	13(41.94)	0.317	0.574	9(32.14)	11(39.29)	0.311	0.577
心血管疾病	20(44.44)	14(45.16)	0.004	0.951	13(46.43)	10(35.71)	0.664	0.415
病理亚型[n(%)]			2.790	0.095			1.198	0.274
腺癌	33(73.33)	17(54.84)			19(67.86)	15(53.57)
其他非鳞癌	12(26.67)	14(45.16)			9(32.14)	13(46.43)
临床分期[n(%)]			0.148	0.700			0.000	1.000
ⅢB期	2(4.44)	2(6.45)			2(7.14)	2(7.14)
Ⅳ期	43(95.56)	29(93.55)			26(92.86)	26(92.86)
驱动基因状态[n(%)]			0.745	0.689			0.410	0.815
KRAS突变	8(17.78)	8(25.81)			6(21.43)	7(25.00)
其他突变	2(4.44)	1(3.23)			2(7.14)	1(3.57)
未知	35(77.78)	22(70.97)			20(71.43)	20(71.43)
铂类药物类型[n(%)]			6.881	0.009			2.276	0.131
卡铂	23(51.11)	25(80.65)			18(64.29)	23(82.14)
顺铂	22(48.89)	6(19.35)			10(35.71)	5(17.86)

表1 两组患者PSM前和PSM后临床资料比较

临床资料	PSM前				PSM后
临床资料	低剂量组(n＝45)	高剂量组(n＝31)	t/χ²值	P值	低剂量组(n＝28)	高剂量组(n＝28)	t/χ²值	P值
男性[n(%)]	26(57.78)	25(80.65)	4.348	0.037	22(78.57)	21(75.00)	0.100	0.752
年龄[岁，(±s)]	67.42±9.54	64.05±6.57	－1.824	0.072	65.93±8.14	65.23±6.38	－0.358	0.722
吸烟状态[n(%)]			0.150	0.699			0.220	0.639
既往或当前吸烟	41(91.11)	29(93.55)			25(89.29)	26(92.86)
从不吸烟	4(8.89)	2(6.45)			3(10.71)	2(7.14)
吸烟指数[n(%)]			0.712	0.399			0.100	0.752
<20包年	8(17.78)	8(25.81)			6(21.43)	7(25.00)
≥20包年	37(82.22)	23(74.19)			22(78.57)	21(75.00)
ECOG PS评分[n(%)]			0.676	0.411			0.080	0.778
0分	12(26.67)	11(35.48)			9(32.14)	10(35.71)
1分	33(73.33)	20(64.52)			19(67.86)	18(64.29)
合并症[n(%)]
高血压	16(35.56)	11(35.48)	0.000	0.995	9(32.14)	9(32.14)	0.000	1.000
糖尿病	7(15.56)	8(25.81)	1.218	0.270	2(7.14)	7(25.00)	3.310	0.069
COPD	16(35.56)	13(41.94)	0.317	0.574	9(32.14)	11(39.29)	0.311	0.577
心血管疾病	20(44.44)	14(45.16)	0.004	0.951	13(46.43)	10(35.71)	0.664	0.415
病理亚型[n(%)]			2.790	0.095			1.198	0.274
腺癌	33(73.33)	17(54.84)			19(67.86)	15(53.57)
其他非鳞癌	12(26.67)	14(45.16)			9(32.14)	13(46.43)
临床分期[n(%)]			0.148	0.700			0.000	1.000
ⅢB期	2(4.44)	2(6.45)			2(7.14)	2(7.14)
Ⅳ期	43(95.56)	29(93.55)			26(92.86)	26(92.86)
驱动基因状态[n(%)]			0.745	0.689			0.410	0.815
KRAS突变	8(17.78)	8(25.81)			6(21.43)	7(25.00)
其他突变	2(4.44)	1(3.23)			2(7.14)	1(3.57)
未知	35(77.78)	22(70.97)			20(71.43)	20(71.43)
铂类药物类型[n(%)]			6.881	0.009			2.276	0.131
卡铂	23(51.11)	25(80.65)			18(64.29)	23(82.14)
顺铂	22(48.89)	6(19.35)			10(35.71)	5(17.86)

图1 NSCLC典型患者治疗前后胸部CT图。图A、B为部分缓解典型病例，女，51岁，低剂量组；图A为治疗前基线CT示右肺实质性占位病灶；图B为治疗后复查CT示原靶病灶显著缩小；图C、D为疾病进展典型病例。男，61岁，高剂量组；图C为治疗前基线CT示右肺下叶实变影；图D为治疗后复查CT示靶病灶体积较基线期明显增大

图2 晚期NSCLC患者组织病理学图(苏木素-伊红染色)。图A为低剂量组肺穿刺活检标本，浸润性非黏液性腺癌，癌组织呈微乳头排列(×10)；图B为高剂量组支气管镜活检标本，纤维间质内见异型上皮样细胞呈微乳头结构浸润(×20)；图C为低剂量组手术标本，支气管周见异型腺体浸润(×10)；图D为高剂量组肺穿刺活检标本，纤维间质内见异型上皮样细胞呈腺管状排列浸润(×20)

图3 两组NSCLC患者Kaplan-Meier生存曲线

图4 两组NSCLC患者亚组分析森林图注：PSM为倾向评分匹配；COPD为慢性阻塞性肺疾病；ECOG PS为东部协作肿瘤组体能状态；KRAS为K-Ras原癌基因

表2 两组NSCLC患者治疗相关不良反应比较[n(%)]

不良反应	1~2级发生率				≥3级发生率
不良反应	低剂量组(n＝28)	高剂量组(n＝28)	χ²值	P值	低剂量组(n＝28)	高剂量组(n＝28)	χ²值	P值
血液学毒性
中性粒细胞减少	2(7.14)	1(3.57)	0.352	0.553	3(10.71)	6(21.43)	1.191	0.275
贫血	17(60.71)	16(57.14)	0.074	0.78612	6(21.43)	2(7.14)	2.333	0.127
血小板减少	6(21.43)	6(21.43)	0.000	1.000	4(14.29)	4(14.29)	0.000	1.000
非血液学毒性
恶心/呕吐	12(42.86)	5(17.86)	4.139	0.042	2(7.14)	1(3.57)	0.352	0.553
乏力	21(75.00)	23(82.14)	0.424	0.515	3(10.71)	0(0.00)	3.170	0.075
肝功能异常	5(17.86)	3(10.71)	0.583	0.445	4(14.29)	1(3.57)	1.976	0.160
肾功能异常	1(3.57)	4(14.29)	1.976	0.160	0(0.00)	0(0.00)	－	－
腹泻	4(14.29)	5(17.86)	0.132	0.716	0(0.00)	0(0.00)	－	－
感染	6(21.43)	7(25.00)	0.100	0.752	3(10.71)	1(3.57)	1.077	0.299
黏膜炎	5(17.86)	1(3.57)	2.987	0.084	2(7.14)	1(3.57)	0.352	0.553

表2 两组NSCLC患者治疗相关不良反应比较[n(%)]

不良反应	1~2级发生率				≥3级发生率
不良反应	低剂量组(n＝28)	高剂量组(n＝28)	χ²值	P值	低剂量组(n＝28)	高剂量组(n＝28)	χ²值	P值
血液学毒性
中性粒细胞减少	2(7.14)	1(3.57)	0.352	0.553	3(10.71)	6(21.43)	1.191	0.275
贫血	17(60.71)	16(57.14)	0.074	0.78612	6(21.43)	2(7.14)	2.333	0.127
血小板减少	6(21.43)	6(21.43)	0.000	1.000	4(14.29)	4(14.29)	0.000	1.000
非血液学毒性
恶心/呕吐	12(42.86)	5(17.86)	4.139	0.042	2(7.14)	1(3.57)	0.352	0.553
乏力	21(75.00)	23(82.14)	0.424	0.515	3(10.71)	0(0.00)	3.170	0.075
肝功能异常	5(17.86)	3(10.71)	0.583	0.445	4(14.29)	1(3.57)	1.976	0.160
肾功能异常	1(3.57)	4(14.29)	1.976	0.160	0(0.00)	0(0.00)	－	－
腹泻	4(14.29)	5(17.86)	0.132	0.716	0(0.00)	0(0.00)	－	－
感染	6(21.43)	7(25.00)	0.100	0.752	3(10.71)	1(3.57)	1.077	0.299
黏膜炎	5(17.86)	1(3.57)	2.987	0.084	2(7.14)	1(3.57)	0.352	0.553

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Propensity score matched analysis of the efficacy and safety of different doses of bevacizumab combined with pemetrexed and platinum-based drugs in the treatment of advanced NSCLC

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Propensity score matched analysis of the efficacy and safety of different doses of bevacizumab combined with pemetrexed and platinum-based drugs in the treatment of advanced NSCLC