Efficacy and influencing factors of anlotinib in treatment of elderly patients with small cell lung cancer after second-line treatment failure

doi:10.3760/cma.j.cn371439-20210520-00005

Abstract

Abstract:

Objective To investigate the efficacy and influencing factors of anlotinib in treatment of elderly patients with small cell lung cancer after second-line treatment failure. Methods A total of 56 elderly patients with small cell lung cancer who were diagnosed and treated in the Tumor Hospital Affiliated to Xinjiang Medical University from September 2018 to February 2020 were collected. All patients were treated with anlotinib capsule after failure of second-line chemotherapy, objective response rate (ORR), disease control rate (DCR) and progression-free survival (PFS) were calculated, and ORR, DCR and PFS of patients with different clinical characteristics were compared. Cox proportional hazards model was used to analyze the factors influencing PFS in elderly patients with small cell lung cancer, and adverse drug reactions were observed. Results After 2 cycles of treatment, the ORR and DCR of 56 elderly patients with small cell lung cancer were 10.7% (6/56) and 53.6% (30/56) respectively. Among them, the ORR and DCR of patients without brain metastasis were 20.8% (5/24) and 75.0% (18/24), which were higher than 3.1% (1/32) and 37.5% (12/32) in patients with brain metastasis, with statistically significant differences (χ²=4.496, P=0.034; χ²=7.754, P=0.005). The ORR and DCR of patients with Eastern Cooperative Oncology Group (ECOG) score of 0-1 were 21.7% (5/23) and 69.6% (16/23), which were higher than those of patients with ECOG score of 2-3 [3.0% (1/33), 42.4% (14/33)], with statistically significant differences (χ²=4.959, P=0.026; χ²=4.014, P=0.045). ORR and DCR were not related to gender, age, clinical stage or smoking status (all P>0.05). The median PFS of 56 patients was 3.8 months. The median PFS of patients aged ≤70 years was 5.0 months, and that of patients aged >70 years was 3.4 months, with a statistically significant difference (χ²=5.452, P=0.020). The median PFS of patients without brain metastasis was 5.1 months, and that of patients with brain metastasis was 3.2 months, with a statistically significant difference (χ²=8.895, P=0.003). The median PFS of patients with ECOG score of 0-1 was 5.0 months, and that of patients with ECOG score of 2-3 was 2.9 months, with a statistically significant difference (χ²=5.923, P=0.015). The median PFS of patients with limited stage was 5.0 months, and that of patients with extensive stage was 3.1 months, with a statistically significant difference (χ²=5.141, P=0.023). Cox multivariate analysis showed that ECOG score (HR=2.522, 95%CI: 1.378-4.615, P=0.003) and brain metastasis or not (HR=0.323, 95%CI: 0.168-0.622, P=0.001) were independent prognostic factors of PFS. During the treatment of anlotinib, the main adverse reactions were grade Ⅰ-Ⅱ, grade Ⅲ-Ⅳ adverse reactions were mainly hypertension and hand-foot syndrome, which improved after drug reduction and symptomatic treatment, and could be tolerated later. The incidence of drug reduction was 3.6% (2/56), and there were no patients with drug interruption or termination of treatment. Conclusion Anlotinib has good short-term efficacy and survival benefits in the treatment of elderly patients with small cell lung cancer after second-line treatment failure. It has good therapeutic effect for patients with low ECOG score and without brain metastasis, and has tolerable adverse reactions and high safety.

Key words: Small cell lung carcinoma, Aged, Anlotinib, Efficacy analysis, Influencing factors

Tao Jie, Wu Mei, Zhang Yan. Efficacy and influencing factors of anlotinib in treatment of elderly patients with small cell lung cancer after second-line treatment failure[J]. Journal of International Oncology, 2022, 49(1): 39-44.

Figures/Tables 4

References 15

[1]	Wang S, Zimmermann S, Parikh K, et al. Current diagnosis and management of small-cell lung cancer[J]. Mayo Clin Proc, 2019, 94(8):1599-1622. DOI: 10.1016/j.mayocp.2019.01.034. doi: 10.1016/j.mayocp.2019.01.034
[2]	Zhao H, Ren D, Liu H, et al. Comparison and discussion of the treatment guidelines for small cell lung cancer[J]. Thorac Cancer, 2018, 9(7):769-774. DOI: 10.1111/1759-7714.12765. doi: 10.1111/1759-7714.12765
[3]	Shao C, He J, Kachroo S, et al. Chemotherapy treatments, costs of care, and survival for patients diagnosed with small cell lung cancer: a SEER-medicare study[J]. Cancer Med, 2019, 8(18):7613-7622. DOI: 10.1002/cam4.2626. doi: 10.1002/cam4.2626
[4]	Lo Russo G, Macerelli M, Platania M, et al. Small-cell lung cancer: clinical management and unmet needs new perspectives for an old problem[J]. Curr Drug Targets, 2017, 18(3):341-362. DOI: 10.2174/1389450117666160502152331. doi: 10.2174/1389450117666160502152331
[5]	Schild SE, Zhao L, Wampfler JA, et al. Small-cell lung cancer in very elderly (≥80 years) patients[J]. Clin Lung Cancer, 2019, 20(4):313-321. DOI: 10.1016/j.cllc.2019.05.007. doi: 10.1016/j.cllc.2019.05.007
[6]	Gao Y, Liu P, Shi R. Anlotinib as a molecular targeted therapy for tumors[J]. Oncol Lett, 2020, 20(2):1001-1014. DOI: 10.3892/ol.2020.11685. doi: 10.3892/ol.2020.11685 pmid: 32724339
[7]	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. doi: 10.1016/j.gene.2018.02.026
[8]	Chen D, Xu J, Zhao Y, et al. Prognostic value of tumor cavitation in extensive-stage small-cell lung cancer patients treated with anlotinib[J]. J Cancer Res Clin Oncol, 2020, 146(2):401-406. DOI: 10.1007/s00432-019-03064-1. doi: 10.1007/s00432-019-03064-1
[9]	刘楠, 吴秀伟, 李烦繁, 等. 安罗替尼三线及以上治疗晚期非小细胞肺癌近期疗效和生命质量分析[J]. 国际肿瘤学杂志, 2019, 46(3):147-152. DOI: 10.3760/cma.j.issn.1673-422X.2019.03.004. doi: 10.3760/cma.j.issn.1673-422X.2019.03.004
[10]	Ruan X, Shi X, Dong Q, et al. Antitumor effects of anlotinib in thyroid cancer[J]. Endocr Relat Cancer, 2019, 26(1):153-164. DOI: 10.1530/ERC-17-0558. doi: 10.1530/ERC-17-0558
[11]	Shen G, Zheng F, Ren D, et al. Anlotini: a novel multi-targeting tyrosine kinase inhibitor in clinical development[J]. J Hematol Oncol, 2018, 11(1):120. DOI: 10.1186/s13045 -018-0664-7. doi: 10.1186/s13045 -018-0664-7
[12]	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. doi: 10.21037/tlcr.2019.09.21
[13]	Han B, Li K, Wang Q, et al. Effect of anlotinib as a third- line or further treatment on overall survival of patients with advanced non-small cell lung cancer: the ALTER 0303 phase 3 randomized clinical trial[J]. JAMA Oncol, 2018, 4(11):1569-1575. DOI: 10.1001/jamaoncol.2018.3039. doi: 10.1001/jamaoncol.2018.3039
[14]	Liu J, Li S, Zhang S, et al. Pretreatment prognostic nutritional index is a prognostic marker for extensive-stage small cell lung cancer patients treated with anlotinib[J]. J Thorac Dis, 2020, 12(10):5765-5773. DOI: 10.21037/jtd-20-755. doi: 10.21037/jtd-20-755
[15]	Yang S, Zhang Z, Wang Q. Emerging therapies for small cell lung cancer[J]. J Hematol Oncol, 2019, 12(1):47. DOI: 10.1186/s13045-019-0736-3. doi: 10.1186/s13045-019-0736-3

临床病理特征	PR	SD			χ²值	P值	疾病控制	χ²值	P值
性别
男	4(10.3)	17(43.5)	18(46.2)	4(10.3)	0.028	0.867	21(53.8)	0.004	0.950
女	2(11.8)	7(41.2)	8(47.0)	2(11.8)			9(52.9)
年龄(岁)
>70	3(11.5)	11(42.3)	12(41.2)	3(11.5)	0.034	0.853	14(53.8)	0.001	0.969
≤70	3(10.0)	13(43.3)	14(46.7)	3(10.0)			16(53.3)
临床分期
局限期	2(9.5)	9(42.9)	10(47.6)	2(9.5)	0.050	0.823	11(52.4)	0.019	0.890
广泛期	4(11.4)	15(42.9)	16(45.7)	4(11.4)			19(54.3)
脑转移
有	1(3.1)	11(34.4)	20(62.5)	1(3.1)	4.496	0.034	12(37.5)	7.754	0.005
无	5(20.8)	13(54.2)	6(25.0)	5(20.8)			18(75.0)
吸烟状况
有	5(12.2)	18(43.9)	18(43.9)	5(12.2)	0.351	0.554	23(56.1)	0.393	0.531
无	1(6.7)	6(40.0)	8(53.3)	1(6.7)			7(46.7)
ECOG评分
0~1	5(21.7)	11(47.9)	7(30.4)	5(21.7)	4.959	0.026	16(69.6)	4.014	0.045
2~3	1(3.0)	13(39.4)	19(57.6)	1(3.0)			14(42.4)

临床特征	β值	SE值	Wald值	HR值	95%CI	P值
年龄	0.475	0.503	0.893	1.609	0.600~4.312	0.345
临床分期	0.589	0.636	0.858	1.802	0.518~6.266	0.354
脑转移	-1.130	0.334	11.439	0.323	0.168~0.622	0.001
ECOG评分	0.925	0.308	8.996	2.522	1.378~4.615	0.003

不良反应	Ⅰ~Ⅱ级
手足综合征	21(37.5)	3(5.4)
咯血	4(7.1)	0(0)
乏力	12(21.4)	0(0)
高血压	9(16.1)	2(3.6)
肝功能损伤	5(8.9)	0(0)
蛋白尿	10(17.9)	0(0)
胃肠道反应	14(25.0)	0(0)