卡瑞利珠单抗联合阿帕替尼对晚期肝癌患者健康相关生活质量的影响

汪蕊; 陈宇佛; 张甜甜; 刘杨; 张珊珊; 李玉梅

doi:10.16766/j.cnki.issn.1674-4152.003106

卡瑞利珠单抗联合阿帕替尼对晚期肝癌患者健康相关生活质量的影响

doi: 10.16766/j.cnki.issn.1674-4152.003106

蚌埠医学院第一附属医院肿瘤内科，安徽蚌埠 233004

基金项目:

安徽省自然科学基金面上项目 2208085MH246

蚌埠医学院第一附属医院杰出青年项目 2019byyfyjq03

蚌埠医学院“512”中青年骨干教师项目 by51201215

详细信息

通讯作者:
汪蕊，E-mail：ruiwang1011@163.com

中图分类号: R735.7 R730.53
计量
- 文章访问数: 151
- HTML全文浏览量: 40
- PDF下载量: 9
- 被引次数: 0
出版历程
- 收稿日期: 2023-03-05
- 网络出版日期: 2023-09-13

Effect of camrelizumab in combination with apatinib on health-related quality of life in patients with advanced liver cancer

Department of Medical Oncology, the First Affiliated Hospital of Bengbu Medical College, Bengbu, Anhui 233004, China

摘要

摘要: 目的分析卡瑞利珠单抗联合阿帕替尼在晚期肝癌(HCC)一线治疗中的疗效及对患者生活质量的影响。方法收集2020年1月—2022年6月在蚌埠医学院第一附属医院接受卡瑞利珠单抗联合阿帕替尼(31例)和阿帕替尼单药(23例)一线治疗晚期HCC患者的临床资料和患者报告结局(EORTC QLQ-C30和HCC18)。分析2组治疗疗效以及对患者生活质量的影响。结果联合组较单药组客观缓解率(22.58% vs. 8.69%，χ²=0.969，P=0.325)和疾病控制率(70.97% vs. 56.52%，χ²=1.208，P=0.271)提高，但差异无统计学意义。联合组中位无疾病进展生存时间(mPFS)较单药组(5.60个月vs. 3.50个月, P=0.002)延长。基线2组C30和HCC18各维度得分相似。4周期后联合组C30情绪(t=2.093，P=0.041)和认知功能(U=193.000，P=0.003)评分高于单药组，恶心呕吐(U=252.500, P=0.039)和食欲丧失(U=244.000, P=0.031)较单药组轻。HCC18躯体改变(U=250.000, P=0.044)和发热(U=237.500, P=0.026)较单药组轻。结论卡瑞利珠单抗联合阿帕替尼一线治疗晚期HCC患者，提高疗效的同时可改善患者健康相关生活质量。
- 肝癌 /
- 卡瑞利珠单抗 /
- 阿帕替尼 /
- 患者报告结局 /
- 健康相关生活质量
Abstract: Objective To evaluate the efficacy of combination therapy with camrelizumab and apatinib as a first-line treatment for advanced hepatocellular carcinoma (HCC) and its impact on patients ' quality of life. Methods The advanced HCC patients who received the first-line treatment of apatinib combined with (31 cases) or without (23 cases) camrelizumab were selected in the First Affiliated Hospital of Bengbu Medical College from January 2020 to June 2022, the clinical data and patient-reported outcome (PRO) scales (EORTC QLQ-C30 and HCC18) were collected. Objective efficacy and the effect on HRQoL were evaluated. Results The combination group was higher in the objective response rate (22.58% vs. 8.69%, χ²=0.969, P=0.325) and disease control rate (70.97% vs. 56.52%, χ²=1.208, P=0.271) compared with the single drug group, however, the difference was not statistically significant. The mPFS in the combination group was prolonged compared to the single drug group (5.60 months vs. 3.50 months, P=0.002). Both groups had similar C30 and HCC18 scores at baseline. After 4 cycles of treatment, C30 emotional (t=2.093, P=0.041) and cognitive function (U=193.000, P=0.003) scores in combination group were higher than those in single drug group. Nausea and vomiting (U=252.500, P=0.039) and loss of appetite (U=244.000, P=0.031) were less severe than single drug group. Body change (U=250.000, P=0.044) and fever (U=237.500, P=0.026) in HCC18 were less severe than those in single drug group. Conclusion Camrelizumab in combination with apatinib for the first-line treatment of advanced HCC patients can improve the efficacy and health-related quality of life of patients.
- Hepatocellular carcinoma /
- Camrelizumab /
- Apatinib /
- Patient-reported outcome /
- Health-related quality of life

HTML全文

图 1 晚期HCC患者PFS Kaplan-Meier生存分析

Figure 1. PFS Kaplan-Meier survival analysis of terminal HCC patients

下载: 全尺寸图片幻灯片

表 1 EORTC QLQ-C30各领域计分方法

Table 1. EORTC QLQ-C30 Scoring Methods in each field

领域(维度)	计算方法	全距(R值)
躯体功能	(Q1+Q2+Q3+Q4+Q5)/5	3
角色功能	(Q6+Q7)/2	3
情绪功能	(Q21+Q22+Q23+Q24)/4	3
认知功能	(Q20+ Q25)/2	3
社会功能	(Q26+Q27)/2	3
总健康水平	(Q29+Q30)/2	6
疲倦	(Q10+Q12+Q26)/3	3
恶心呕吐	(Q14+Q15)/2	3
疼痛	(Q9+Q19)/2	3
气促	Q8	3
失眠	Q11	3
食欲丧失	Q13	3
便秘	Q16	3
腹泻	Q17	3
经济困难	Q28	3

下载: 导出CSV

表 2 EORTC QLQ-HCC18各维度计分方法

Table 2. EORTC QLQ-HCC18 Scoring Methods for each dimensions

维度	计算方法	全距(R值)
腹胀	(Q4-1)×100/3	3
躯体改变	[(Q3+Q5)/2-1]×100/3	3
黄疸	[(Q6+Q7)/2-1]×100/3	3
疼痛	[(Q8+Q9)/2-1]×100/3	3
发热	[(Q10+Q11)/2-1]×100/3	3
营养改变	[(Q1+Q2+Q12+Q13+Q14)/5-1]×100/3	6
疲乏	[(Q15+Q16+Q17)/3-1]×100/3	3
性生活改变	(Q18-1)×100/3	3

下载: 导出CSV

表 3 2组HCC患者基线特征(例)

Table 3. Baseline characteristics of HCC patients in 2 groups(cases)

项目	联合治疗组(n=31)	单药组(n=23)	χ²值	P值	项目	联合治疗组(n=31)	单药组(n=23)	χ²值	P值
年龄(岁)			0.773	0.379	AFP(ng/mL)			0.969	0.324
≥70	4	6			< 400	12	12
< 70	27	17			≥400	19	11
性别			0.119	0.729	血管侵犯			1.305	0.253
男性	23	18			有	14	14
女性	8	5			无	17	9
ECOG评分			0.825	0.662	肝外转移			0.947	0.331
0	10	5			有	19	17
1	13	12			无	12	6
2	8	6			HBV感染			0.424	0.515
Child-Pugh			0.003	0.957	有	24	16
A(5~6分)	20	15			无	7	7
B(7分)	11	8			既往局部治疗			0.118	0.943
BCLC分期			0.124	0.724	手术切除	9	7
B	12	10			消融	5	4
C	19	13			TACE	14	9

下载: 导出CSV

表 4 2组HCC患者近期疗效比较

Table 4. Comparison of short-term efficacy of HCC patients in 2 groups

组别	例数	完全缓解(例)	部分缓解(例)	疾病稳定(例)	疾病进展(例)	客观缓解率(%)	疾病控制率(%)
联合治疗组	31	0	7	15	9	22.58(7/31)	70.97(22/31)
单药组	23	0	2	11	10	8.69(2/23)	56.52(13/23)
χ²值						0.969	1.208
P值						0.325	0.271

下载: 导出CSV

表 5 4周期后2组HCC患者量表得分比较(分)

Table 5. Comparison of scale scores of HCC patients in 2 groups after 4 cycles(points)

量表维度	4周期后联合治疗组(n=31)	4周期后单药组(n=23)	统计量	P值
EORTC QLQ-C30
总体健康水平[M(P₂₅, P₇₅)]	50.00(33.33, 58.33)	41.67(33.33, 50.00)	288.500^a	0.226
躯体功能[M(P₂₅, P₇₅)]	66.67(60.00, 80.00)	60.00(46.47, 73.33)	271.500^a	0.135
角色功能[M(P₂₅, P₇₅)]	66.67(33.33, 83.33)	50.00(33.33, 66.67)	290.000^a	0.242
情绪功能(x±s)	56.99±19.14	46.38±17.38	2.093^b	0.041
认知功能[M(P₂₅, P₇₅)]	66.67(66.67, 83.33)	50.00(50.00, 66.67)	193.000^a	0.003
社会功能[M(P₂₅, P₇₅)]	50.00(33.33, 66.67)	50.00(33.33, 50.00)	255.500^a	0.069
疲劳(x±s)	32.26±19.95	34.30±13.36	0.424^b	0.673
恶心呕吐[M(P₂₅, P₇₅)]	16.67(16.67, 33.33)	33.33(16.67, 50.00)	252.500^a	0.039
疼痛[M(P₂₅, P₇₅)]	16.67(16.67, 33.33)	33.33(16.67, 33.33)	261.500^a	0.089
气促[M(P₂₅, P₇₅)]	0.00(0.00, 33.33)	0.00(0.00, 33.33)	344.500^a	0.918
失眠[M(P₂₅, P₇₅)]	33.33(0.00, 33.33)	33.33(0.00, 66.67)	296.500^a	0.278
食欲丧失[M(P₂₅, P₇₅)]	33.33(0.00, 33.33)	33.33(0.00, 66.67)	244.000^a	0.031
便秘[M(P₂₅, P₇₅)]	0.00(0.00, 33.33)	0.00(0.00, 33.33)	300.500^a	0.301
腹泻[M(P₂₅, P₇₅)]	0.00(0.00, 33.33)	0.00(0.00, 33.33)	324.500^a	0.554
经济困难[M(P₂₅, P₇₅)]	33.33(33.33, 66.67)	66.67(33.33, 66.67)	347.000^a	0.866
EORTC QLQ-HCC18
腹胀[M(P₂₅, P₇₅)]	33.33(0.00, 33.33)	33.33(0.00, 33.33)	328.000^a	0.605
躯体改变[M(P₂₅, P₇₅)]	0.00(0.00, 16.67)	16.67(0.00, 33.33)	250.000^a	0.044
黄疸[M(P₂₅, P₇₅)]	0.00(0.00, 16.67)	16.67(0.00, 33.33)	288.000^a	0.202
疼痛[M(P₂₅, P₇₅)]	16.67(0.00, 16.67)	16.67(0.00, 33.33)	337.000^a	0.732
发热[M(P₂₅, P₇₅)]	16.67(0.00, 16.67)	16.67(0.00, 33.33)	237.500^a	0.026
营养改变[M(P₂₅, P₇₅)]	20.00(13.33, 33.33)	26.67(13.33, 46.67)	293.000^a	0.267
疲乏[M(P₂₅, P₇₅)]	22.22(22.22, 33.33)	33.33(11.11, 33.33)	342.000^a	0.801
性生活改变[M(P₂₅, P₇₅)]	33.33(0.00, 33.33)	33.33(0.00, 33.33)	325.000^a	0.582
注：^a为U值，^b为t值。

下载: 导出CSV

参考文献(20)

[1]	李照, 朱继业. 《原发性肝癌诊疗指南(2022年版)》解读[J]. 临床肝胆病杂志, 2022, 38(5): 1027-1029. doi: 10.3969/j.issn.1001-5256.2022.05.010 LI Z, ZHU J Y. Interpretation of Standard for diagnosis and treatment of primary liver cancer(2022 edition)[J]. Journal of Clinical Hepatology, 2022, 38(5): 1027-1029 doi: 10.3969/j.issn.1001-5256.2022.05.010
[2]	NORMAN E M L, WEIL J, PHILIP J. Hepatocellular carcinoma and its impact on quality of life: a review of the qualitative literature[J]. Eur J Cancer Care (Engl), 2022, 31(6): e13672. DOI: 10.1111/ecc.13672.
[3]	李萍, 刘文红, 赵萌, 等. 原发性肝癌肝动脉化疗栓塞术术前营养风险筛查的意义及个体化营养干预效果分析[J]. 中华全科医学, 2021, 19(7): 1087-1090. doi: 10.16766/j.cnki.issn.1674-4152.001991 LI P, LIU W H, ZHAO M, et al. Significance of nutritional risk screening before transcatheter arterial chemoembolization for primary liver cancer and the effect of individualised nutritional intervention[J]. Chinese Journal of General Practice, 2021, 19(7): 1087-1090. doi: 10.16766/j.cnki.issn.1674-4152.001991
[4]	SILVEIRA A, SEQUEIRA T, GONCALVES J, et al. Patient reported outcomes in oncology: changing perspectives-a systematic review[J]. Health Qual Life Outcomes, 2022, 20(1): 82. doi: 10.1186/s12955-022-01987-x
[5]	YOUNOSSI Z, AGGARWAL P, SHRESTHA I, et al. The burden of non-alcoholic steatohepatitis: a systematic review of health-related quality of life and patient-reported outcomes[J]. JHEP Rep, 2022, 4(9): 100525. DOI: 10.1016/j.jhepr.2022.100525.
[6]	RIMASSA L, DANESI R, PRESSIANI T, et al. Management of adverse events associated with tyrosine kinase inhibitors: improving outcomes for patients with hepatocellular carcinoma[J]. Cancer Treat Rev, 2019, 77: 20-28. doi: 10.1016/j.ctrv.2019.05.004
[7]	ZOU H M, LI M, LEI Q, et al. Economic burden and quality of life of hepatocellular carcinoma in greater China: a systematic review[J]. Front Public Health, 2022, 10: 801981. DOI: 10.3389/fpubh.2022.801981.
[8]	CARROZZONO D, PATIERNO C, GUIDI J, et al. Clinimetric criteria for patient-reported outcome measures[J]. Psychother Psychosom, 2021, 90(4): 222-232. doi: 10.1159/000516599
[9]	FREEMANTLE N, MOLLON P, MEYER T, et al. Quality of life assessment of cabozantinib in patients with advanced hepatocellular carcinoma in the CELESTIAL trial[J]. Eur J Cancer, 2022, 168: 91-98. DOI: 10.1016/j.ejca.2022.03.021.
[10]	XIA S J, PAN Y, LIANG Y L, et al. The microenvironmental and metabolic aspects of sorafenib resistance in hepatocellular carcinoma[J]. EBioMedicine, 2020, 51: 102610. DOI: 10.1016/j.ebiom.2019.102610.
[11]	CHEN S, CAO Q, WEN W, et al. Targeted therapy for hepatocellular carcinoma: challenges and opportunities[J]. Cancer Lett, 2019, 460: 1-9. DOI: 10.1016/j.canlet.2019.114428.
[12]	SANGRO B, SAROBE P, HERVAS-STUBBS S, et al. Advances in immunotherapy for hepatocellular carcinoma[J]. Nat Rev Gastroenterol Hepatol, 2021, 18(8): 525-543. doi: 10.1038/s41575-021-00438-0
[13]	REN Z G, XU J M, BAI Y X, et al. Sintilimab plus a bevacizumab biosimilar (IBI305) versus sorafenib in unresectable hepatocellular carcinoma (ORIENT-32): a randomised, open-label, phase 2-3 study[J]. Lancet Oncol, 2021, 22(7): 977-990. doi: 10.1016/S1470-2045(21)00252-7
[14]	LIU Z Y, LIU X, LIANG J X, et al. Immunotherapy for hepatocellular carcinoma: current status and future prospects[J]. Front Immunol, 2021, 12: 765101. DOI: 10.3389/fimmu.2021.765101.
[15]	GALLE P R, FINN R S, QIN S, et al. Patient-reported outcomes with atezolizumab plus bevacizumab versus sorafenib in patients with unresectable hepatocellular carcinoma (IMbrave150): an open-label, randomised, phase 3 trial[J]. Lancet Oncol, 2021, 22(7): 991-1001. doi: 10.1016/S1470-2045(21)00151-0
[16]	KELLEY R K, SANGRO B, HARRIS W, et al. Safety, efficacy, and pharmacodynamics of tremelimumab plus durvalumab for patients with unresectable hepatocellular carcinoma: randomized expansion of a phase Ⅰ/Ⅱ study[J]. J Clin Oncol, 2021, 39(27): 2991-3001. doi: 10.1200/JCO.20.03555
[17]	FIRKINS J L, TARTER R, DRIESSBACK M, et al. A closer look at quality of life in the hepatocellular carcinoma literature[J]. Qual Life Res, 2021, 30(6): 1525-1535. doi: 10.1007/s11136-021-02789-2
[18]	PALA L, SALA I, ORIECUIA C, et al. Association of anticancer immune checkpoint inhibitors with patient-reported outcomes assessed in randomized clinical trials: a systematic review and meta-analysis[J]. JAMA Netw Open, 2022, 5(8): e2226252. DOI: 10.1001/jamanetworkopen.2022.26252.
[19]	周慧, 林颖, 周国进, 等. 《将患者报告结局纳入临床研究的伦理考量: PRO伦理指南》解读[J]. 中国全科医学, 2023, 26(4): 395-400. https://www.cnki.com.cn/Article/CJFDTOTAL-QKYX202304016.htm ZHOU H, LIN Y, ZHOU G J, et al. Interpretation of Ethical Considerations for the Inclusion of Patient-Reported Outcomes in Clinical Research(the PRO Ethics Guidelines)[J]. Chinese General Practice, 2023, 26(4): 395-400. https://www.cnki.com.cn/Article/CJFDTOTAL-QKYX202304016.htm
[20]	LEITH A, KⅡSKINEN U, GIRVAN A C, et al. Physician and patient reported symptom concordance and association with quality of life in hepatocellular carcinoma[J]. Future Oncol, 2022, 18(33): 3727-3740. doi: 10.2217/fon-2022-0202