Clinical efficacy and safety of camrelizumab and sintilimab in the treatment of advanced non-small cell lung cancer

Abstract

Abstract:

ObjectiveTo compare the clinical efficacy of camrelizumab and sintilimab in the treatment of advanced non-small cell lung cancer （NSCLC）， and to explore its impact on tumor marker levels and immune function index， as well as to perform safety analysis.MethodsA total of 87 patients with advanced NSCLC who were treated in Hai'an People's Hospital of Jiangsu Province from May 2019 to May 2021 were selected as the research objects. According to the treatment scheme， the patients were divided into camrelizumab group （n=41） and sintilimab group （n=46）. The clinical efficacy， prognosis， tumor marker levels， immune function index and immune related adverse reactions of the two groups were compared.ResultsThere were no statistically significant differences in objective response rate [48.78% （20/41）vs.39.13% （18/46），χ²=0.82，P=0.365] or disease control rate [78.05% （32/41）vs.71.74% （33/46），χ²=0.46，P=0.499] in both camrelizumab and sintilimab group. The median progression-free survival （PFS） in the camrelizumab group was 9.1 months， and the median overall survival （OS） was 15.4 months. The median PFS in the sintilimab group was 9.7 months， and the median OS was 15.7 months. There were no statistically significant differences in median PFS and median OS between the two groups （χ²=0.18，P=0.633；χ²=0.15，P=0.697）. Before treatment， there were no statistically significant differences in carcinoembryonic antigen （CEA） [（47.68±8.12） ng/mlvs.（49.03±8.70） ng/ml，t=0.75，P=0.458]， cytokeratin 19 fragment antigen 21-1 （CYFRA21-1） [（18.06±3.41） ng/mlvs.（17.25±3.78） ng/ml，t=1.05，P=0.299]， and carbohydrate antigen 125 （CA125） [（72.26±21.06） U/mlvs.（74.03±22.10） U/ml，t=0.38，P=0.704] levels between the camrelizumab group and sintilimab group. After treatment， there were no statistically significant differences in CEA [（28.11±7.68） ng/mlvs.（27.63±5.71） ng/ml，t=0.33，P=0.740]， CYFRA21-1 [（9.29±1.88） ng/mlvs.（9.06±1.80） ng/ml，t=0.15，P=0.814]， and CA125 [（61.39±21.22） U/mlvs.（60.51±11.03） U/ml，t=0.25，P=0.806] levels between the two groups， but CEA， CYFRA21-1， and CA125 levels decreased after treatment compared with those before treatment in both groups （allP<0.05）. Before treatment， there were no statistically significant differences in T cells CD4⁺[（41.15±3.24）%vs.（41.17±2.90）%，t=0.03，P=0.976]， CD8⁺[（68.82±3.94）%vs.（70.06±4.08）%，t=1.44，P=0.154]， and CD4⁺/CD8⁺（1.88±0.33vs.1.76±0.25，t=1.92，P=0.058） between the two groups. After treatment， there were no statistically significant differences in T cells CD4⁺[（47.08±3.22）%vs.（48.53±5.07）%，t=1.57，P=0.120]， CD8⁺[（61.22±1.67）%vs.（61.45±1.66）%，t=0.64，P=0.522]， and CD4⁺/CD8⁺（2.31±0.17vs.2.36±0.12，t=1.60，P=0.114） between the two groups， while T cells CD8⁺was lower than that before treatment， and CD4⁺as well as CD4⁺/CD8⁺were higher than those before treatment in both groups （allP<0.05）. The overall incidence of adverse reactions in the sintilimab group [10.87% （5/46）] was lower than that in the camrelizumab group [31.71% （13/41）]， and with a statistically significance （χ²=5.74，P=0.016）.ConclusionThe clinical efficacy of camrelizumab and sintilimab in NSCLC patients is basically the same， the impacts of which on tumor markers and immune function are comparable， but the safety of sintilimab is better than that of camrelizumab.

Key words:Carcinoma,non-small-cell lung,Treatment outcome,Drug-related side effects and adverse reactions,Camrelizumab,Sintilimab

Yan Aiting, Wang Cuizhu, Liu Chungui, Lu Xiaomin. Clinical efficacy and safety of camrelizumab and sintilimab in the treatment of advanced non-small cell lung cancer[J]. Journal of International Oncology, 2024, 51(3): 137-142.

Figures/Tables5

一般临床资料	卡瑞利珠单抗组（n=41）	信迪利单抗组（n=46）	χ²/t/ Z值	P值
性别
男	25（60.98）	27（58.70）	0.05	0.829
女	16（39.02）	19（41.30）	0.05	0.829
年龄（岁）	61.83±7.12	60.97±7.20	0.94	0.362
BMI（kg/m²）	25.40±2.02	25.21±2.21	0.96	0.329
TMB
低突变	5（12.20）	6（13.04）
中突变	11（26.83）	13（28.26）	0.21	0.830
高突变	25（60.98）	27（58.70）
PD-L1阳性表达率>1%
是	24（58.54）	28（60.87）	0.05	0.825
否	17（41.46）	18（39.13）	0.05	0.825
吸烟史
有	33（80.49）	30（65.22）	2.53	0.112
无	8（19.51）	16（34.78）	2.53	0.112

组别	CEA（ng/ml）			CA125（U/ml）
卡瑞利珠单抗组（n=41）	47.68±8.12	28.11±7.68^a	18.06±3.41	9.29±1.88^a	72.26±21.06	61.39±21.22^a
信迪利单抗组（n=46）	49.03±8.70	27.63±5.71^a	17.25±3.78	9.06±1.80^a	74.03±22.10	60.51±11.03^a
t值	0.75	0.33	1.05	0.15	0.38	0.25
P值	0.458	0.740	0.299	0.814	0.704	0.806

组别	CD4⁺（%）			CD4⁺/CD8⁺
卡瑞利珠单抗组（n=41）	41.15±3.24	47.08±3.22^a	68.82±3.94	61.22±1.67^a	1.88±0.33	2.31±0.17^a
信迪利单抗组（n=46）	41.17±2.90	48.53±5.07^a	70.06±4.08	61.45±1.66^a	1.76±0.25	2.36±0.12^a
t值	0.03	1.57	1.44	0.64	1.92	1.60
P值	0.976	0.120	0.154	0.522	0.058	0.114

组别	皮肤反应	疲劳	高血糖	原发性肾上腺功能减退	甲状腺功能异常	合计
卡瑞利珠单抗组（n=41）	3（7.32）	4（9.76）	2（4.88）	1（2.44）	3（7.32）	13（31.71）
信迪利单抗组（n=46）	1（2.17）	2（4.35）	1（2.17）	0（0）	1（2.17）	5（10.87）
χ²值						5.74
P值						0.016

References18

[1]	Chen PX, Liu YH, Wen YK, et al. Non-small cell lung cancer in China[J].Cancer Commun (Lond),2022,42(10): 937-970. DOI:10.1002/cac2.12359.
[2]	Hill H, Robinson M, Lu L, et al. Venous thromboembolism incidence and risk factors in non-small cell lung cancer patients receiving first-line systemic therapy[J].Thromb Res,2021,208: 71-78. DOI:10.1016/j.thromres.2021.10.014. pmid:34742139
[3]	Chu T, Zhong R, Zhong H, et al. Phase 1b study of sintilimab plus anlotinib as first-line therapy in patients with advanced NSCLC[J].J Thorac Oncol,2021,16(4): 643-652. DOI:10.1016/j.jtho.2020.11.026. pmid:33524601
[4]	韩宝惠. 中华医学会肺癌临床诊疗指南(2018版)[J].肿瘤研究与临床,2018,30(12): 793-824. DOI:10.3760/cma.j.issn.1006-9801.2018.12.001.
[5]	杨学宁, 吴一龙. 实体瘤治疗疗效评价标准-RECIST[J].循证医学,2004,4(2): 85-90, 111. DOI:10.3969/j.issn.1671-5144.2004.02.012.
[6]	Badiee PRA, Maritz MF, Dmochowska N, et al. Intratumoral anti-PD-1 nanoformulation improves its biodistribution[J].ACS Appl Mater Interfaces,2022,14(14): 15881-15893. DOI:10.1021/acsami.1c22479.
[7]	Zhou JY, Du ZH, Liang Y, et al. Benefits and risks of PD-1/PD-L1 inhibitors for recurrent small cell lung cancer: a systematic review and meta-analysis[J].Crit Rev Oncol Hematol,2024,193: 104222. DOI:10.1016/j.critrevonc.2023.104222.
[8]	John T, Sakai H, Ikeda S, et al. First-line nivolumab plus ipili-mumab combined with two cycles of chemotherapy in advanced non-small cell lung cancer: a subanalysis of Asian patients in CheckMate 9LA[J].Int J Clin Oncol,2022,27(4): 695-706. DOI:10.1007/s10147-022-02120-0.
[9]	Guo JY, Guo JY, Cheng BB, et al. Synergistic effect of stereotactic radiotherapy combined with karelizumab on patients with advanced NSCLC[J].J Healthc Eng,2022,2022: 7875627. DOI:10.1155/2022/7875627.
[10]	de Kock R, Borne BVD, Soud MYE, et al. Circulating biomarkers for monitoring therapy response and detection of disease progression in lung cancer patients[J].Cancer Treat Res Commun,2021,28: 100410. DOI:10.1016/j.ctarc.2021.100410.
[11]	Schalper KA, Rodriguez-Ruiz ME, Diez-Valle R, et al. Neoadjuvant nivolumab modifies the tumor immune microenvironment in resec-table glioblastoma[J].Nat Med,2019,25(3): 470-476. DOI:10.1038/s41591-018-0339-5. pmid:30742120
[12]	Clevers MR, Kastelijn EA, Peters BJM, et al. Evaluation of serum biomarker CEA and CA-125 as immunotherapy response predictors in metastatic non-small cell lung cancer[J].Anticancer Res,2021,41(2): 869-876. DOI:10.21873/anticanres.14839. pmid:33517292
[13]	Zhao W, Liu YL, Kong FL, et al. Correlations of pathological stage and prognosis of NSCLC patients with changes in serum CEA and CYFRA 21-1 and CT characteristics[J].Panminerva Med,2020,62(1): 67-69. DOI:10.23736/S0031-0808.19.03642-5. pmid:31144789
[14]	Chen C, Wu B, Zhang CY, et al. Immune-related adverse events associated with immune checkpoint inhibitors: an updated comprehensive disproportionality analysis of the FDA adverse event repor-ting system[J].Int Immunopharmacol,2021,95: 107498. DOI:10.1016/j.intimp.2021.107498.
[15]	陈昕怡, 赵程程, 席庆. 信迪利单抗联合化疗治疗局部晚期/转移性非小细胞肺癌的快速卫生技术评估[J].临床药物治疗杂志,2023,21(10): 69-74. DOI:10.3969/j.issn.1672-3384.2023.10.013.
[16]	杨建奇, 曹文淼, 吴银霞, 等. 卡瑞利珠单抗或信迪利单抗联合仑伐替尼治疗肝癌的效果及对肿瘤标志物的影响[J].肝脏,2022,27(10): 1080-1083. DOI:10.3969/j.issn.1008-1704.2022.10.009.
[17]	Zhao J, Zhao L, Guo W, et al. Efficacy, safety, and biomarker analysis of neoadjuvant camrelizumab and apatinib in patients with resectable NSCLC: a phase 2 clinical trial[J].J Thorac Oncol,2023,18(6): 780-791. DOI:10.1016/j.jtho.2023.02.019. pmid:36870519
[18]	Lei J, Zhao JB, Gong L, et al. Neoadjuvant camrelizumab plus platinum-based chemotherapy vs chemotherapy alone for Chinese patients with resectable stage ⅢA or ⅢB (T₃N₂) non-small cell lung cancer: the TD-FOREKNOW randomized clinical trial[J].JAMA Oncol,2023,9(10): 1348-1355. DOI:10.1001/jamaoncol.2023.2751.