Clinical efficacy and optimal dose of apatinib combined with chemotherapy in patients with advanced non-small cell lung cancer

Abstract

Abstract:

aObjectiveTo explore the clinical efficacy of different doses of apatinib combined with chemotherapy in patients with advanced non-small cell lung cancer (NSCLC) and the adverse reactions.MethodsA total of 69 patients with NSCLC diagnosed in the No. 901 Hospital of the Chinese People's Liberation Army Joint Logistics Support Force were selected from January 2018 to June 2020, and were divided into chemotherapy alone group (docetaxel+cisplatin was used), apatinib group A [apatinib (0.25 g)+docetaxel+cisplatin was used] and apatinib group B [apatinib (0.50 g)+docetaxel+cisplatin was used] according to random number table method, with 23 cases in each group. The objective response rate (ORR), disease control rate (DCR), median overall survival (OS), median progression-free survival (PFS), and incidences of adverse reactions were compared between the three groups of patients.ResultsOne patients in the apatinib group B withdrew from the study due to acute myocardial infarction. After 4 cycless of treatment, the ORR of the patients in the chemotherapy alone group, apatinib group A and apatinib group B were 17.39% (4/23), 47.83% (11/23) and 54.55% (12/22) respectively, with a statistically significant difference (χ²=7.41,P=0.024). The ORR of the apatinib group B was higher than that of the chemotherapy alone group, with a statistically significant difference (χ²=6.77,P=0.009). There were no statistically significant differences in ORR between the apatinib group A and chemotherapy alone group, the apatinib group A and apatinib group B (χ²=4.85,P=0.028;χ²=0.20,P=0.652). The DCR of the patients in the three groups were 47.83% (11/23), 78.26% (18/23) and 86.36% (19/22) respectively, with a statistically significant difference (χ²=9.03, P=0.011). The DCR of the apatinib group B was higher than that of the chemotherapy alone group, with a statistically significant difference (χ²=7.52,P=0.006). There were no statistically significant differences in DCR between the apatinib group A and the chemotherapy alone group, the apatinib group A and apatinib group B (χ²=4.57,P=0.033;χ²=0.51,P=0.477). The median OS of the patients in the three groups were 6.8, 9.2 and 9.9 months respectively, with a statistically significant different (χ²=8.91,P=0.022). Compared with the chemotherapy alone group, the median OS of the apatinib group A and apatinib group B were significantly prolonged, with statistically significant differences (χ²=7.25,P=0.036;χ²=8.60,P=0.029). Compared with the apatinib group A, the median OS of the apatinib group B was prolonged, but there was no statistically significant different (χ²=1.54,P=0.201). The median PFS of the patients in the three groups were 5.2, 7.7 and 8.2 months respectively, with a statistically significant different (χ²=8.79,P=0.026). Compared with the chemotherapy alone group, the median PFS of the apatinib group A and apatinib group B were significantly prolonged, with statistically significant differences (χ²=7.01,P=0.039;χ²=8.36,P=0.031). Compared with the apatinib A group, the median PFS of the apatinib group B was prolonged, but there was no statistically significant different (χ²=1.68,P=0.186). There were statistically significant differences in the incidences of fatigue [34.78% (8/23)vs. 65.22% (15/23)vs. 72.73% (16/22),χ²=7.50,P=0.024], hypertension [4.35%(1/23)vs.34.78%(8/23)vs.68.18%(15/22),χ²=20.07,P<0.001], hand-foot syndrome [4.35% (1/23)vs.43.48%(10/23)vs.72.73%(16/22),χ²=22.28,P<0.001] and oral mucositis [8.70% (2/23)vs.39.13%(9/23)vs.72.73%(16/22),χ²=19.26,P<0.001] among the three groups. Compared with the chemotherapy alone group, the incidences of hypertension and hand-foot syndrome in the apatinib group A and the incidences of fatigue, hypertension, hand-foot syndrome and oral mucositis in the apatinib group B were increased, with statistically significant differences (χ²=6.77,P=0.009;χ²=9.68,P=0.002;χ²=6.51,P=0.011;χ²=20.00,P<0.001;χ²=22.37,P<0.001;χ²=19.21,P<0.001).ConclusionApatinib (0.50 g) combined with chemotherapy has better short-term efficacy than chemotherapy alone in advanced NSCLC. Apatinib (0.25 g) and apatinib (0.50 g) can prolong the survival of patients, but increasing the treatment dose can not achieve longer survival benefit.

Key words:Lung neoplasms,Drug therapy,Apatinib,Efficacy evaluation,Dosimetry factors

Gao Shile, Lu Donghui, Liu Meiqin, Xu Xingjun, Ma Huan, Zhang Yu. Clinical efficacy and optimal dose of apatinib combined with chemotherapy in patients with advanced non-small cell lung cancer[J]. Journal of International Oncology, 2022, 49(3): 140-145.

Figures/Tables5

临床病理特征	单纯化疗组 (n=23)	阿帕替尼 A组 (n=23)	阿帕替尼 B组 (n=23)	F/χ²值	P值
年龄(岁)	61.6±8.8	63.5±9.2	59.3±7.6	1.02	0.365
性别
男	12	13	14	0.35	0.838
女	11	10	9
病理类型
鳞状细胞癌	12	11	14	0.82	0.665
腺癌	11	12	9
临床分期
Ⅲ期	12	10	13	0.81	0.666
Ⅳ期	11	13	10
驱动基因状态
突变型	7	6	8
野生型	9	8	8	0.71	0.950
未知状态	7	9	7
治疗线数
一线	6	5	6
二线	9	8	10	0.90	0.925
三线及以上	8	10	7
吸烟史
有	6	9	8	0.91	0.634
无	17	14	15

组别	CR	PR	SD	PD	客观缓解	疾病控制
单纯化疗组(n=23)	0(0)	4(17.39)	7(30.43)	11(47.83)	4(17.39)^a	11(47.83)^b
阿帕替尼A组(n=23)	1(4.35)	10(43.48)	7(30.43)	5(21.74)	11(47.83)^c	18(78.26)^d
阿帕替尼B组(n=22)	1(4.55)	11(50.00)	7(31.82)	3(13.64)	12(54.55)^e	19(86.36)^f
χ²值					7.41	9.03
P值					0.024	0.011

分组	白细胞减少	血小板减少	贫血	乏力	高血压	手足综合征	口腔黏膜炎	蛋白尿
单纯化疗组(n=23)	10(43.48)	5(21.74)	7(30.43)	8(34.78)	1(4.35)^a	1(4.35)^b	2(8.70)	0(0)
阿帕替尼A组(n=23)	11(47.83)	6(26.07)	8(34.78)	15(65.22)	8(34.78)	10(43.48)	9(39.13)	4(17.39)
阿帕替尼B组(n=22)	11(50.00)	5(22.73)	8(36.36)	16(72.73)^c	15(68.18)^d	16(72.73)^e	16(72.73)^f	4(18.18)
χ²值		0.20	0.13	0.19	7.50	20.07	22.28	19.26	5.19
P值		0.905	0.936	0.909	0.024	<0.001	<0.001	<0.001	0.102

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