卡瑞利珠单抗联合白蛋白紫杉醇二线治疗晚期食管鳞状细胞癌的疗效和安全性

doi:10.3760/cma.j.cn371439-20210409-00129

摘要/Abstract

摘要：

目的评价卡瑞利珠单抗联合白蛋白紫杉醇二线治疗晚期食管鳞状细胞癌(ESCC)患者的疗效和安全性。方法研究对象为2019年5月12日至2020年8月20日皖西卫生职业学院附属医院肿瘤科收治的一线治疗失败的晚期或转移性ESCC患者72例,根据患者意愿分别给予卡瑞利珠单抗联合白蛋白紫杉醇(试验组,n=45)或二线化疗(多西他赛或伊立替康,对照组,n=27)。分析患者的客观缓解率(ORR)、疾病控制率(DCR)、不良事件发生率、总生存期(OS)、无进展生存期(PFS)。结果试验组和对照组ORR分别为26.7%(12/45)、7.4%(2/27),差异有统计学意义(χ²=3.996,P=0.046);DCR分别为48.9%(22/45)、29.6%(8/27),差异无统计学意义(χ²=2.575,P=0.109)。在不良事件方面,试验组患者耐受性更好,3级及以上不良事件发生率更低[28.9%(13/45) vs. 55.6%(15/27)],较对照组减少了48%,差异有统计学意义(χ²=5.049,P=0.025)。对照组有1例患者发生了与治疗相关的死亡。试验组中位OS为8.9个月(95%CI为7.9~9.8),对照组中位OS为6.5个月(95%CI为5.6~7.3),差异有统计学意义(χ²=5.068,P=0.024)。试验组中位PFS为2.2个月(95%CI为1.6~2.7),对照组中位PFS为1.8个月(95%CI为1.5~2.0),差异有统计学意义(χ²=4.799,P=0.028)。结论卡瑞利珠单抗联合白蛋白紫杉醇二线治疗晚期ESCC患者的疗效确切,安全性可耐受,可能成为晚期ESCC二线治疗的潜在方案。

关键词: 食管肿瘤, 卡瑞利珠单抗, 治疗结果

Abstract:

Objective To evaluate the efficacy and safety of camrelizumab combined with albumin paclitaxel in second-line treatment of advanced esophageal squamous cell carcinoma (ESCC). Methods Seventy-two patients with advanced or metastatic ESCC who had failed first-line treatment admitted to the Department of Oncology of the Affiliated Hospital of West Anhui Health Vocational College from May 12, 2019 to August 20, 2020 were enrolled. The patients were given camrelizumab combined with albumin paclitaxel (the experimental group, n=45) or second-line chemotherapy (docetaxel or irinotecan, the control group, n=27) according to patients' preference. Besides, the objective response rate (ORR), disease control rate (DCR), incidence of adverse events, overall survival (OS) and progress free survival (PFS) were assessed. Results The ORR of the experimental group and the control group were 26.7% (12/45) and 7.4% (2/27) respectively, with a statistically significant difference (χ ²=3.996, P=0.046). The DCR of the two groups were 48.9% (22/45) and 29.6% (8/27) respectively, with no statistically significant difference (χ ²=2.575, P=0.109). In terms of adverse events, the experimental group was better tolerated, and the incidence of grade 3 or above adverse events was lower [28.9% (13/45) vs. 55.6% (15/27)], which was 48% lower than that of the control group, with a statistically significant difference (χ ²=5.049, P=0.025). One patient in the control group had a treatment-related death. The median OS was 8.9 months (95%CI: 7.9-9.8) in the experimental group and 6.5 months (95%CI: 5.6-7.3) in the control group, with a statistically significant difference (χ ²=5.068, P=0.024). The median PFS was 2.2 months (95%CI: 1.6-2.7) in the experimental group and 1.8 months (95%CI: 1.5-2.0) in the control group, with a statistically significant difference (χ ²=4.799, P=0.028). Conclusion Camrelizumab combined with albumin paclitaxel in second-line treatment of advanced ESCC patients has proven efficacy and tolerable safety, which may be a potential second-line treatment for advanced ESCC.

Key words: Esophageal neoplasms, Camrelizumab, Treatment outcome

张玉萍, 吴德平. 卡瑞利珠单抗联合白蛋白紫杉醇二线治疗晚期食管鳞状细胞癌的疗效和安全性[J]. 国际肿瘤学杂志, 2021, 48(11): 649-654.

Zhang Yuping, Wu Deping. Efficacy and safety of camrelizumab combined with albumin paclitaxel as second-line therapy for advanced esophageal squamous cell carcinoma[J]. Journal of International Oncology, 2021, 48(11): 649-654.

图/表 4

表1

表2

图1

图2

参考文献 17

[1]	Sung H, Ferlay J, Siegel RL, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries[J]. CA Cancer J Clin, 2021, 71(3):209-249. DOI: 10.3322/caac.21660. doi: 10.3322/caac.v71.3
[2]	Abnet CC, Arnold M, Wei WQ. Epidemiology of esophageal squamous cell carcinoma[J]. Gastroenterology, 2018, 154(2):360-373. DOI: 10.1053/j.gastro.2017.08.023. doi: 10.1053/j.gastro.2017.08.023
[3]	Hirano H, Kato K. Systemic treatment of advanced esophageal squamous cell carcinoma: chemotherapy, molecular-targeting therapy and immunotherapy[J]. Jpn J Clin Oncol, 2019, 49(5):412-420. DOI: 10.1093/jjco/hyz034. doi: 10.1093/jjco/hyz034
[4]	Mo H, Huang J, Xu J, et al. Safety, anti-tumour activity, and pharmacokinetics of fixed-dose SHR-1210, an anti-PD-1 antibody in advanced solid tumours: a dose-escalation, phase 1 study[J]. Br J Cancer, 2018, 119(5):538-545. DOI: 10.1038/s41416-018-0100-3. doi: 10.1038/s41416-018-0100-3
[5]	Nowicki TS, Hu-Lieskovan S, Ribas A. Mechanisms of resistance to PD-1 and PD-L1 blockade[J]. Cancer J, 2018, 24(1):47-53. DOI: 10.1097/ppo.0000000000000303. doi: 10.1097/PPO.0000000000000303
[6]	杨科, 李峻岭, 乔英凯, 等. 白蛋白结合型紫杉醇为基础的化疗方案治疗复发性小细胞肺癌的临床疗效[J]. 癌症进展, 2019, 17(12):1395-1399. DOI: 10.11877/j.issn.1672-1535.2019.17.12.09.
[7]	王芸, 张耕源, 罗长江, 等. 白蛋白结合型紫杉醇联合吉西他滨治疗进展期胰腺癌临床效果的Meta分析[J]. 临床肝胆病杂志, 2019, 35(5):1041-1046. DOI: 10.3969/j.issn.1001-5256.2019.05.021.
[8]	Kato K, Cho BC, Takahashi M, et al. Nivolumab versus chemotherapy in patients with advanced oesophageal squamous cell carcinoma refractory or intolerant to previous chemotherapy (ATTRACTION-3): a multicentre, randomised, open-label, phase 3 trial[J]. Lancet Oncol, 2019, 20(11):1506-1517. DOI: 10.1016/s1470-2045(19)30626-6. doi: S1470-2045(19)30626-6 pmid: 31582355
[9]	Kojima T, Shah MA, Muro K, et al. Randomized phase Ⅲ KEYNOTE-181 study of pembrolizumab versus chemotherapy in advanced esophageal cancer[J]. J Clin Oncol, 2020, 38(35):4138-4148. DOI: 10.1200/jco.20.01888. doi: 10.1200/JCO.20.01888
[10]	Huang J, Xu J, Chen Y, et al. Camrelizumab versus investigator's choice of chemotherapy as second-line therapy for advanced or metastatic oesophageal squamous cell carcinoma (ESCORT): a multicentre, randomised, open-label, phase 3 study[J]. Lancet Oncol, 2020, 21(6):832-842. DOI: 10.1016/s1470-2045(20)30110-8. doi: S1470-2045(20)30110-8 pmid: 32416073
[11]	Huang J, Xu B, Mo H, et al. Safety, activity, and biomarkers of SHR-1210, an anti-PD-1 antibody, for patients with advanced esophageal carcinoma[J]. Clin Cancer Res, 2018, 24(6):1296-1304. DOI: 10.1158/1078-0432.Ccr-17-2439. doi: 10.1158/1078-0432.CCR-17-2439 pmid: 29358502
[12]	Fang W, Yang Y, Ma Y, et al. Camrelizumab (SHR-1210) alone or in combination with gemcitabine plus cisplatin for nasopharyngeal carcinoma: results from two single-arm, phase 1 trials[J]. Lancet Oncol, 2018, 19(10):1338-1350. DOI: 10.1016/s1470-2045(18)30495-9. doi: 10.1016/S1470-2045(18)30495-9
[13]	Nie J, Wang C, Liu Y, et al. Addition of low-dose decitabine to anti-PD-1 antibody camrelizumab in relapsed/refractory classical hodgkin lymphoma[J]. J Clin Oncol, 2019, 37(17):1479-1489. DOI: 10.1200/jco.18.02151. doi: 10.1200/JCO.18.02151
[14]	侯莉娜, 迪娜·索力提肯, 郭智, 等. PD-1抑制剂单药治疗与联合化疗/靶向治疗晚期恶性肿瘤的疗效及安全性比较[J]. 国际肿瘤学杂志, 2020, 47(4):193-198. DOI: 10.3760/cma.j.cn371439-20190731-00001.
[15]	Chen X, Ma L, Wang X, et al. Reactive capillary hemangiomas: a novel dermatologic toxicity following anti-PD-1 treatment with SHR-1210[J]. Cancer Biol Med, 2019, 16(1):173-181. DOI: 10.20892/j.issn.2095-3941.2018.0172. doi: 10.20892/j.issn.2095-3941.2018.0172
[16]	Song Y, Wu J, Chen X, et al. A single-arm, multicenter, phase Ⅱ study of camrelizumab in relapsed or refractory classical hodgkin lymphoma[J]. Clin Cancer Res, 2019, 25(24):7363-7369. DOI: 10.1158/1078-0432.Ccr-19-1680. doi: 10.1158/1078-0432.CCR-19-1680
[17]	Finlay WJJ, Coleman JE, Edwards JS, et al. Anti-PD1 ‘SHR-1210’ aberrantly targets pro-angiogenic receptors and this polyspecificity can be ablated by paratope refinement[J]. MAbs, 2019, 11(1):26-44. DOI: 10.1080/19420862.2018.1550321. doi: 10.1080/19420862.2018.1550321

一般情况	试验组(n=45)	对照组(n=27)	χ²值	P值
年龄(岁)
≥65	31(68.9)	19(70.4)	0.017	0.895
<65	14(31.1)	8(29.6)
性别
男	41(91.1)	25(92.6)	<0.001	>0.999
女	4(8.9)	2(7.4)
ECOG评分
0	7(15.6)	3(11.1)	0.031	0.860
1	38(84.4)	24(88.8)
疾病分期
局部晚期	5(11.1)	2(7.4)	0.011	0.918
远处转移	40(88.9)	25(92.5)
转移器官数
1	21(46.7)	11(40.7)	0.240	0.624
≥2	24(53.3)	16(59.3)
既往治疗
手术	9(20.0)	7(25.9)
放疗	21(46.7)	14(51.8)	-	-
化疗	42(93.3)	27(100)

不良事件		试验组(n=45)										对照组(n=27)
不良事件		1~2级		3级	4级		5级			≥3级		1~2级	3级		4级	5级	≥3级
脱发	3(6.7)		0(0)			0(0)		0(0)	0(0)		3(11.1)			0(0)	0(0)	0(0)	0(0)
白细胞减少	6(13.3)		1(2.2)			0(0)		0(0)	1(2.2)		10(37.0)			3(11.1)	0(0)	0(0)	3(11.1)
中性粒细胞减少	5(11.1)		0(0)			0(0)		0(0)	0(0)		8(29.6)			2(7.4)	1(3.7)	0(0)	3(11.1)
血小板减少	2(4.4)		0(0)			0(0)		0(0)	0(0)		3(11.1)			0(0)	0(0)	0(0)	0(0)
贫血	5(11.1)		1(2.2)			0(0)		0(0)	1(2.2)		10(37.0)			2(7.4)	0(0)	0(0)	2(7.4)
纳差	6(13.3)		0(0)			0(0)		0(0)	0(0)		7(25.9)			2(7.4)	0(0)	0(0)	2(7.4)
恶心/呕吐	6(13.3)		0(0)			0(0)		0(0)	0(0)		11(40.7)			1(3.7)	0(0)	0(0)	1(3.7)
腹泻	1(2.2)		2(4.4)			0(0)		0(0)	2(4.4)		8(29.6)			1(3.7)	0(0)	0(0)	1(3.7)
疲劳/乏力	10(26.7)		2(4.4)			0(0)		0(0)	2(4.4)		9(33.3)			2(7.4)	0(0)	0(0)	2(7.4)
发热	5(11.1)		0(0)			0(0)		0(0)	0(0)		3(11.1)			0(0)	0(0)	0(0)	0(0)
肺炎	2(4.4)		2(4.4)			0(0)		0(0)	2(4.4)		0(0)			0(0)	0(0)	0(0)	0(0)
甲状腺功能减退	9(20.0)		3(6.7)			0(0)		0(0)	3(6.7)		0(0)			0(0)	0(0)	0(0)	0(0)
反应性毛细血管增生症	31(68.9)		2(4.4)			0(0)		0(0)	2(4.4)		0(0)			0(0)	0(0)	0(0)	0(0)
死亡	0(0)		0(0)			0(0)		0(0)	0(0)		0(0)			0(0)	0(0)	1(3.7)	1(3.7)