Observation on the therapeutic effect of atezolizumab combined with anlotinib in treating advanced non-small cell lung cancer

Abstract

Abstract:

ObjectiveTo explore the efficacy of atezolizumab combined with anlotinib in treating advanced non-small cell lung cancer （NSCLC）.MethodsA total of 80 patients with advanced NSCLC treated in the Baoding No.2 Central Hospital from September 2019 to September 2023 after second-line treatment were selected as research subjects. Patients who received only anlotinib treatment were included in the monotherapy group （n=40）， while patients who received atezolizumab combined with anlotinib treatment were included in the combination group （n=40）. The clinical efficacy and serum levels of carcinoembryonic antigen （CEA） and vascular endothelial growth factor （VEGF） of the two groups were compared. Kaplan-Meier survival curve was used to analyze the survival of the two groups. The functional assessment of cancer therapy-lung cancer （FACT-L） was used to assess the quality of life of patients in both groups before and after treatment. The incidence of adverse reactions was compared between the two groups.ResultsAfter four cycles of treatment， the objective response rate （ORR） of the combination group was 37.50% （15/40）， which was higher than that of the monotherapy group [17.50% （7/40）]， with a statistically significant difference （χ²=4.01，P=0.045）. The disease control rates （DCRs） of the two groups were 85.00% （34/40） and 75.00% （30/40）， respectively， with no statistically significant difference （χ²=1.25，P=0.264）. Before treatment， the CEA levels in combination group and monotherapy group were （10.18±2.15） and （10.14±2.02） μg/L， and the VEGF levels were （804.04±46.58） and （809.10±43.63） ng/L， respectively， with no statistically significant difference （bothP>0.05）. After treatment， the serum CEA levels of patients in combination group and monotherapy group were （4.35±1.05） and （6.63±1.37） μg/L， and the VEGF levels were （431.26±50.19） and （549.92±55.27） ng/L， respectively， with statistically significant differences （t=8.35，P<0.001；t=10.05，P<0.001）， and the levels of serum CEA and VEGF in the two groups after treatment were lower than before treatment （t=32.47，P<0.001；t=21.73，P<0.001；t=88.65，P<0.001；t=58.27，P<0.001）. Survival analysis showed that the median progression-free survival （PFS） of the monotherapy group and the combination group were 4.12 and 6.06 months， respectively， with a statistically significant difference （χ²=17.70，P<0.001）， the median overall survival （OS） were 11.8 and 12.7 months， respectively， with no statistically significant difference （χ²=3.09，P=0.079）. Before treatment， the FACT-L scores of patients in combination group and monotherapy group were 61.20±6.98 and 60.52±7.14， respectively， with no statistically significant difference （t=0.43，P=0.668）. After treatment， the FACT-L scores of the two groups were 83.24±9.38 and 74.58±7.86， respectively， with a statistically significant difference （t=4.48，P<0.001）， and the FACT-L scores of the two groups after treatment were all higher than before treatment （t=29.36，P<0.001；t=21.51，P<0.001）. During treatment， the total incidence of drug-related adverse reactions in two groups was 42.50% （17/40） and 55.00% （22/40）， respectively， with no statistically significant difference （χ²=1.25，P=0.263）.ConclusionsAtezolizumab combined with anlotinib in the treatment of advanced NSCLC can enhance the short-term efficacy， prolong the PFS of patients， improve the quality of life， and the related adverse reactions are tolerable.

Key words:Carcinoma， non-small-cell lung,Atezolizumab,Anlotinib,Treatment outcome

Zhao Fang, Jiang Guorong, Shi Shuyue, Xiao Jian, Ma Shaolin, Li Runpu. Observation on the therapeutic effect of atezolizumab combined with anlotinib in treating advanced non-small cell lung cancer[J]. Journal of International Oncology, 2025, 52(8): 495-501.

Figures/Tables6

组别	性别	年龄（岁）	TNM分期		病理类型	合并高血压	吸烟史
联合组（n=40）	28（70.00）	12（30.00）	62.11±9.76	10（25.00）	30（75.00）		26（65.00）	14（35.00）	5（12.50）	16（40.00）
单药组（n=40）	26（65.00）	14（35.00）	61.80±9.19	9（22.50）	31（77.50）		29（72.50）	11（27.50）	6（15.00）	18（45.00）
χ²/t值	0.23	0.16	0.07		0.52	0.11	0.21
P值	0.633	0.884	0.793		0.469	0.745	0.651

组别	CR	PR	SD	PD	客观缓解	疾病控制
联合组（n=40）	0（0）	15（37.50）	19（47.50）	6（15.00）	15（37.50）	34（85.00）
单药组（n=40）	0（0）	7（17.50）	23（57.50）	10（25.00）	7（17.50）	30（75.00）
χ²值					4.01	1.25
P值					0.045	0.264

组别	CEA（μg/L）	t值	P值	VEGF（ng/L）	t值	P值
联合组（n=40）	10.18±2.15	4.35±1.05	32.47	<0.001	804.04±46.58	431.26±50.19	88.65	<0.001
单药组（n=40）	10.14±2.02	6.63±1.37	21.73	<0.001	809.10±43.63	549.92±55.27	58.27	<0.001
t值	0.09	8.35			0.50	10.05
P值	0.932	<0.001			0.617	<0.001

组别	FACT-L评分	t值	P值
联合组（n=40）	61.20±6.98	83.24±9.38	29.36	<0.001
单药组（n=40）	60.52±7.14	74.58±7.86	21.51	<0.001
t值	0.43	4.48
P值	0.668	<0.001

组别	毛细血管扩张症	高血压	乏力	手足综合征	总发生情况
联合组（n=40）	9（22.50）	3（7.50）	2（5.00）	3（7.50）	17（42.50）
单药组（n=40）	8（20.00）	6（15.00）	4（10.00）	4（10.00）	22（55.00）
χ²值					1.25
P值					0.263

References24

[1]	Mithoowani H, Febbraro M. Non-small-cell lung cancer in 2022: a review for general practitioners in oncology[J].Curr Oncol,2022,29(3): 1828-1839. DOI:10.3390/curroncol29030150.
[2]	Dohopolski M, Gottumukkala S, Gomez D, et al. Radiation therapy in non-small-cell lung cancer[J].Cold Spring Harb Perspect Med,2021,11(10): a037713. DOI:10.1101/cshperspect.a037713.
[3]	方涛, 雷想, 宋兵. 阿特珠单抗在肺癌治疗中的研究进展[J].中国胸心血管外科临床杂志,2022,29(1): 114-120. DOI:10.7507/1007-4848.202008037.
[4]	Wang L, He Z, Yang S, et al. The impact of previous therapy strategy on the efficiency of anlotinib hydrochloride as a third-line treatment on patients with advanced non-small cell lung cancer (NSCLC): a subgroup analysis of ALTER0303 trial[J].Transl Lung Cancer Res,2019,8(5): 575-583. DOI:10.21037/tlcr.2019.09.21.
[5]	Lin B, Song X, Yang D, et al. Anlotinib inhibits angiogenesis via suppressing the activation of VEGFR2, PDGFRβ and FGFR1[J].Gene,2018,654: 77-86. DOI:10.1016/j.gene.2018.02.026. pmid:29454091
[6]	李笑萍, 王江涛, 花小梅. 安罗替尼联合免疫检查点抑制剂二线及以上治疗驱动基因阴性晚期非小细胞肺癌的疗效和安全性[J].癌症进展,2024,22(6): 644-647. DOI:10.11877/j.issn.1672-1535.2024.22.06.13.
[7]	Ettinger DS, Wood DE, Aisner DL, et al. Non-small cell lung cancer, version 5.2017, NCCN clinical practice guidelines in oncology[J].J Natl Compr Canc Netw,2017,15(4): 504-535. DOI:10.6004/jnccn.2017.0050.
[8]	Schwartz LH, Litière S, de Vries E, et al. RECIST 1.1-update and clarification: from the RECIST committee[J].Eur J Cancer,2016,62: 132-137. DOI:10.1016/j.ejca.2016.03.081. pmid:27189322
[9]	Bray F, Laversanne M, Sung H, et al. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries[J].CA Cancer J Clin,2024,74(3): 229-263. DOI:10.3322/caac.21834.
[10]	Grant C, Hagopian G, Nagasaka M. Neoadjuvant therapy in non-small cell lung cancer[J].Crit Rev Oncol Hematol,2023,190(1): 104080. DOI:10.1016/j.critrevonc.2023.104080.
[11]	Wu YL, Lu S, Cheng Y, et al. Nivolumab versus docetaxel in a predominantly Chinese patient population with previously treated advanced NSCLC: CheckMate 078 randomized phase Ⅲ clinical trial[J].J Thorac Oncol,2019,14(5): 867-875. DOI:10.1016/j.jtho.2019.01.006.
[12]	Mosca M, Conci N, Di Federico A, et al. First-generation epidermal growth factor receptor inhibitors plus antiangiogenic drugs versus third-generation epidermal growth factor receptor inhibitors in advanced non-small-cell lung cancer: a meta-analysis[J].JCO Precis Oncol,2023,7(1): e2300073. DOI:10.1200/PO.23.00073.
[13]	Liu Y, Cheng Y, Li K, et al. Effect of prior thoracic radiotherapy on prognosis in relapsed small cell lung cancer patients treated with anlotinib: a subgroup analysis of the ALTER 1202 trial[J].Transl Lung Cancer Res,2021,10(9): 3793-3806. DOI:10.21037/tlcr-21-632.
[14]	Smith EA, Belote RL, Cruz NM, et al. Receptor tyrosine kinase inhibition leads to regression of acral melanoma by targeting the tumor microenvironment[J].J Exp Clin Cancer Res,2024,43(1): 317. DOI:10.1186/s13046-024-03234-1.
[15]	Li S. Anlotinib: a novel targeted drug for bone and soft tissue sarcoma[J].Front Oncol,2021,11: 664853. DOI:10.3389/fonc.2021.664853.
[16]	谢红霞, 左金辉, 廖冬颖, 等. PD-L1抑制剂在非小细胞肺癌中的应用[J].国际肿瘤学杂志,2022,49(2): 111-115. DOI:10.3760/cma.j.cn371439-20210121-00018.
[17]	刘雨晴, 袁淑敏, 祁晓星, 等. 安罗替尼联合免疫检查点抑制剂治疗晚期非小细胞肺癌的疗效及安全性[J].中国临床医生杂志,2023,51(4): 447-450. DOI:10.3969/j.issn.2095-8552.2023.04.020.
[18]	车雅丹, 李丽霞. 小分子抗血管生成药物在晚期乳腺癌中的研究进展[J].实用医学杂志,2023,39(22): 2866-2871. DOI:10.3969/j.issn.1006-5725.2023.22.002.
[19]	Wang P, Fang X, Yin T, et al. Efficacy and safety of anti-PD-1 plus anlotinib in patients with advanced non-small-cell lung cancer after previous systemic treatment failure—a retrospective study[J].Front Oncol,2021,11: 628124. DOI:10.3389/fonc.2021.628124.
[20]	Zhang W, Zhang C, Yang S, et al. Immune checkpoint inhibitors plus anlotinib versus anlotinib alone as third-line treatment in advanced non-small-cell lung cancer: a retrospective study[J].Future Oncol,2021,17(31): 4091-4099. DOI:10.2217/fon-2021-0649. pmid:34254526
[21]	许佳佳, 刘小兰, 潘桢婕, 等. 安罗替尼单用及分别与免疫抑制剂和化疗药物联合应用治疗晚期肺癌对比观察[J].山东医药,2022,62(6): 52-55. DOI:10.3969/j.issn.1002-266X.2022.09.012.
[22]	Li S, Wang H. Research progress on mechanism and management of adverse drug reactions of anlotinib[J].Drug Des Devel Ther,2023,17: 3429-3437. DOI:10.2147/DDDT.S426898.
[23]	Nan X, Xie C, Zhu Q, et al. Hand-foot syndrome and survival in patients with advanced non-small-cell lung cancer receiving anlotinib: a subgroup analysis of data from the ALTER 0303 study[J].Int J Clin Oncol,2020,25(8): 1492-1498. DOI:10.1007/s10147-020-01683-0. pmid:32447474
[24]	Chen Q, Zheng K, Xu M, et al. Anlotinib combined with radiotherapy and chemotherapy for recurrent pelvic osteosarcoma treatment: a case report and literature review[J].Front Oncol,2023,13: 1283932. DOI:10.3389/fonc.2023.1283932.