甲胎蛋白应答评价索拉非尼联合卡瑞利珠单抗治疗晚期肝细胞癌的效果分析

王星; 张韬

doi:10.3969/j.issn.1001-5256.2023.04.015

甲胎蛋白应答评价索拉非尼联合卡瑞利珠单抗治疗晚期肝细胞癌的效果分析

DOI: 10.3969/j.issn.1001-5256.2023.04.015

王星,
张韬^, ,

新疆医科大学第一附属医院感染·肝病中心，乌鲁木齐 830054

基金项目:

新疆维吾尔自治区自然科学基金 (2021D01C322)

伦理学声明：本研究方案经由新疆医科大学第一附属医院伦理委员会审批，批号：K202212-10，所纳入患者均签署知情同意书。

利益冲突声明：本研究不存在研究者、伦理委员会成员、受试者监护人以及公开研究成果有关的利益冲突。

作者贡献声明：王星负责课题设计，资料分析，撰写论文；张韬负责指导撰写文章并最后定稿。

详细信息

通信作者:
张韬, zhang1tao3@163.com (ORCID: 0000-0003-1272-675X)

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出版历程
- 收稿日期: 2022-08-31
- 录用日期: 2022-10-27
- 出版日期: 2023-04-20

Value of alpha-fetoprotein response in evaluating the efficacy of sorafenib combined with camrelizumab in treatment of advanced hepatocellular carcinoma

Xing WANG,
Tao ZHANG^{,
,}

Center of Infectious Diseases and Hepatology, The First Affiliated Hospital of Xinjiang Medical University, Urumqi 830054, China

Research funding:

Natural Science Foundation of Xinjiang Uygur Autonomous Region (2021D01C322)

More Information

Corresponding author: ZHANG Tao, zhang1tao3@163.com (ORCID: 0000-0003-1272-675X)

摘要

摘要: 目的探讨甲胎蛋白(AFP)应答在索拉非尼联合卡瑞利珠单抗治疗晚期肝细胞癌中的临床疗效及安全性。方法选取2020年9月—2022年2月于新疆医科大学第一附属医院接受索拉非尼联合卡瑞利珠单抗治疗的48例晚期肝细胞癌患者的临床资料，按照治疗后AFP应答水平进行分组：应答组(治疗6~8个月时，与基础AFP比较，AFP下降率＞20%，n=32)；无应答组(治疗6~8个月时，与基础AFP比较，AFP下降率≤20%, n=16)。计量资料组间比较采用Mann-Whitney U检验；计数资料组间比较采用χ²检验。绘制生存曲线，行Cox单因素/多因素回归分析得到与OS相关的独立危险因素。比较两组患者无进展生存时间、总生存期与治疗效果。结果两组患者中均未观察到达到临床缓解的病例。AFP应答组的客观有效率(21.88% vs 0)和疾病控制率(84.38% vs 43.75%) 均高于无应答组(χ²值分别为2.530、6.668，P值分别为0.112、0.010)。应答组无进展生存期(9.9个月)、总生存期(13.8个月)均高于无应答组(6.8个月、11.1个月)。AFP早期无应答(HR=2.624，95%CI：1.097~6.277，P=0.030)及肝外转移(HR=0.392，95%CI：0.157~0.978，P=0.045)与较短的无进展生存期独立相关。未出现因不良反应导致停药事件的发生。结论 AFP早期应答在预测索拉非尼联合卡瑞利珠单抗治疗晚期肝细胞癌患者疗效及预后方面具有较高的临床价值。
- 癌, 肝细胞 /
- 甲胎蛋白类 /
- 索拉非尼
Abstract: Objective To investigate the value of alpha-fetoprotein (AFP) response in evaluating the clinical efficacy and safety of sorafenib combined with camrelizumab in the treatment of advanced hepatocellular carcinoma (HCC). Methods Clinical data were collected from 48 patients with advanced HCC who were treated with sorafenib combined with camrelizumab in The First Affiliated Hospital of Xinjiang Medical University from September 2020 to February 2022, and according to the level of AFP response after treatment, they were divided into response group with 32 patients (AFP after 6-8 months of treatment was reduced by more than 20% compared with baseline AFP) and non-response group with 16 patients (AFP after 6-8 months of treatment was reduced by less than 20% compared with baseline AFP). The Mann-Whitney U test was used for comparison of continuous data between groups, and the chi-square test was used for comparison of categorical data between groups. Survival curves were plotted, and univariate and multivariate Cox regression analyses were used to investigate the independent risk factors for overall survival (OS). Progression free survival (PFS) time, OS time, and treatment outcome were compared between the two groups. Results No patient achieved clinical remission in either group. Compared with the non-response group, the response group had significantly higher objective response rate (21.88% vs 0, χ²=2.530, P=0.112) and disease control rate (84.38% vs 43.75%, χ²=6.668, P=0.010). Compared with the non-response group, the response group had longer PFS time (9.9 months vs 6.8 months) and OS time (13.8 months vs 11.1 months). Early non-response of AFP (hazard ratio [HR]=2.624, 95% confidence interval [CI]: 1.097-6.277, P=0.030) and extrahepatic metastasis (HR=0.392, 95%CI: 0.157-0.978, P=0.045) were independently associated with a shorter PFS time. No adverse event leading to drug withdrawal was observed in the study. Conclusion Early AFP response has a high clinical value in predicting the efficacy of sorafenib combined with camrelizumab in the treatment of advanced HCC and the prognosis of such patients.
- Carcinoma, Hepatocellular /
- alpha-Fetoproteins /
- Sorafenib

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图 1 AFP早期应答组和无应答组的PFS和OS曲线

注：a, PFS; b, OS。

Figure 1. PFS and OS curves in the AFP early responder and non-responder groups

下载: 全尺寸图片幻灯片

表 1 基线特征的比较

Table 1. Comparison of baseline characteristics

变量	应答组(n=32)	无应答组(n=16)	统计值	P值
性别[例(%)]			χ²=1.497	0.239
男	23(71.80)	15(93.80)
女	9(28.00)	1(6.30)
年龄[例(%)]			χ²=0.381	0.573
≥60岁	13(40.60)	8(50.00)
＜60岁	19(59.40)	8(50.00)
基线AFP(ng/mL)	353.31(113.10~1 015.87)	1 616.89(92.08~2 000.00)	Z=-2.203	0.088
AST(U/L)	49.10(37.26~97.53)	63.56(42.36~91.18)	Z=-0.787	0.331
ALT(U/L)	48.89(36.42~68.00)	39.73(30.73~68.11)	Z=-0.437	0.662
TBil(mol/L)	20.85(17.51~30.61)	17.69(15.46~19.48)	Z=-3.040	0.002
Alb(g/L)	38.59(31.32~41.34)	36.19(33.53~37.88)	Z=-0.262	0.793
PLT(×10⁹/L)	112.00(60.25~163.25)	141.50(100.50~191.25)	Z=-1.488	0.137
Hb(g/L)	138.00(125.25~147.75)	123.50(107.50~146.00)	Z=-1.969	0.049
PT(s)	13.20(12.60~14.50)	13.20(12.00~13.85)	Z=-0.941	0.347
INR	1.16(1.11~1.25)	1.15(1.06~1.20)	Z=-0.733	0.463
病因[例(%)]			χ²=0.034	0.854
HBV	30(93.80)	14(87.50)
HCV	2(6.30)	2(12.50)
ECOG评分[例(%)]			χ²=0.671	0.413
0	16(50.0)	6(37.50)
1	16(50.0)	10(62.50)
肝硬化[例(%)]	26(81.25)	15(93.75)	χ²=0.523	0.470
腹水[例(%)]	27(84.38)	14(87.50)	χ²=0.000	1.000
远处转移[例(%)]	7(21.88)	5(68.75)	χ²=0.125	0.480
门静脉癌栓[例(%)]	8(25.00)	8(25.00)	χ²=3.000	0.083

下载: 导出CSV

表 2 AFP早期应答组和无应答组的临床疗效比较

Table 2. Comparison of clinical outcomes between the early responders and non-responders of AFP

临床疗效	应答组(n=32)	无应答组(n=16)
CR(例)	0	0
PR(例)	7	0
SD(例)	20	7
PD(例)	5	9
ORR	21.88%	0
DCR	84.38%	43.75%

下载: 导出CSV

表 3 PFS相关的单因素和多因素分析

Table 3. PFS-related univariate and multifactorial analyses

变量	单因素分析		多因素分析
变量	HR(95%CI)	P值	HR(95%CI)	P值
年龄(≥60岁vs＜60岁)	1.152(0.479~2.771)	0.751
AFP(早期无应答vs有应答)	2.751(1.162~6.517)	0.021	2.624(1.097~6.277)	0.030
腹水(有vs无)	0.588(0.193~1.796)	0.351
HBsAg(阳性vs阴性)	0.750(0.171~3.282)	0.702
肝外转移(有vs无)	2.715(1.102~6.690)	0.030	0.392(0.157~0.978)	0.045
门静脉癌栓(有vs无)	1.791(0.748~4.289)	0.191
ECOG评分(0 vs 1)	0.228(0.701~4.423)	0.228
Child-Pugh分级(A级vs B级)	0.275(0.326~2.440)	0.275

下载: 导出CSV

表 4 OS相关的单因素和多因素分析

Table 4. OS-related univariate and multifactorial analyses

变量	单因素分析		多因素分析
变量	HR(95%CI)	P值	HR(95%CI)	P值
年龄(≥60岁vs＜60岁)	1.138(0.467~2.772)	0.776
AFP(早期无应答vs有应答)	2.639(1.113~6.260)	0.028	2.364(0.957~5.835)	0.062
腹水(有vs无)	0.587(0.191~1.800)	0.351
HBsAg(阳性vs阴性)	0.596(0.133~2.669)	0.498
肝外转移(有vs无)	2.921(1.129~7.235)	0.021
门静脉癌栓(有vs无)	1.941(0.810~4.651)	0.137	2.940(1.152~7.506)	0.024
ECOG评分(1 vs 0)	3.050(1.118~8.318)	0.029	3.000(1.045~8.608)	0.041
Child-Pugh分级(A级vs B级)	0.325(0.053~2.487)	0.279

下载: 导出CSV

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