卡瑞利珠单抗联合化疗及靶向治疗在复发、转移及初治晚期宫颈癌中的疗效与安全性分析：一项回顾性队列研究

doi:10.19401/j.cnki.1007-3639.2025.06.006

摘要/Abstract

摘要：

背景与目的： 复发、转移及初治晚期宫颈癌的治疗仍面临挑战，免疫治疗联合化疗及靶向治疗初步显示出临床获益，但现有证据有限。本研究旨在评估卡瑞利珠联合化疗及靶向治疗对复发、转移及初治晚期宫颈癌患者预后的影响。方法： 回顾性分析2019—2025年复旦大学附属肿瘤医院闵行院区收治的符合纳入和排除标准的复发、转移及初治晚期宫颈癌患者的临床资料，使用对数秩检验进行生存分析，并通过单因素和多因素Cox比例风险回归模型分析探讨预后的相关因素。本研究获得了复旦大学附属肿瘤医院闵行院区伦理委员会的审批[伦理批号：（2024）伦审第（015）号]并豁免患者知情同意。结果： 本研究共纳入130例患者。根据是否接受卡瑞利珠单抗分为观察组70例（卡瑞利珠单抗，可联合化疗与靶向治疗）和对照组60例（化疗联合靶向治疗）。观察组的客观缓解率（objective response rate，ORR）为72.9%，疾病控制率（disease control rate，DCR）为80.0%，显著优于未接受免疫治疗的对照组（ORR=20.0%，χ²=36.1，P<0.001；DCR=40.0%，χ²=21.8，P<0.001）。观察组未达到中位无进展生存期（progression-free survival，PFS），优于对照组（中位PFS=7.0个月，P<0.001），Cox比例风险回归模型分析显示卡瑞利珠单抗治疗是PFS的独立保护因素（P<0.001），而患者的年龄、复发转移部位、初始治疗方式和病理学类型对PFS无显著影响。观察组有29例患者（41.4%）发生≥3级不良反应，主要包括血管增生、甲减、过敏和腹泻等。结论： 在复发、转移及初治晚期宫颈癌的治疗中，卡瑞利珠单抗治疗显著改善了患者的治疗效果和预后，延长了患者的PFS。尽管存在一定比例的≥3级不良反应，但整体上患者可接受。在实际临床中，免疫治疗联合化疗及靶向治疗为患者提供了更为有效的治疗选择。

关键词: 宫颈癌, 免疫治疗, 化疗, 靶向治疗, 复发, 转移, 初治晚期, 预后

Abstract:

Background and purpose: The treatment of recurrent, metastatic, and treatment-naïve advanced cervical cancer remains challenging. Immunotherapy in combination with chemotherapy and targeted therapy has shown preliminary clinical benefits, however, current evidence remains limited. This study aimed to evaluate the impact of camrelizumab combined with chemotherapy and targeted therapy on the prognosis of patients with recurrent, metastatic, and treatment-naïve advanced cervical cancer. Methods: In this study, we conducted a retrospective analysis of the clinical data from 130 patients with recurrent, metastatic, and treatment-naïve advanced cervical cancer admitted to Minhang Branch of Fudan University Shanghai Cancer Center from 2019 to 2025. The patients were categorized into the observation group (n=70), which included those who received camrelizumab with or without chemotherapy and targeted therapy, and the control group (n=60), including those who received chemotherapy and targeted therapy. Survival analysis was performed using the log-rank test, and univariate and multivariate Cox regression analyses were conducted to explore prognostic factors. This study was approved by the Ethics Committee of the Minhang Branch of Fudan University Shanghai Cancer Center[Approval number: (2024) Review No. (015)] and all informed consents were exempted. Results: The objective response rate (ORR) in the observation group was 72.9%, and the disease control rate (DCR) was 80.0%, which were significantly higher than those in the control group with an ORR of 20.0% (χ²=36.1, P<0.001) and a DCR of 40.0% (χ²=21.8, P<0.001). The median progression-free survival (PFS) in the observation group was not reached, significantly longer than that in the control group of 7.0 months (P<0.001). Multivariate Cox regression analysis identified camrelizumab treatment as an independent protective factor for PFS (P<0.001). Age, site of recurrence/metastasis, initial treatment approach, and histopathological type were not significantly associated with PFS. In the observation group, adverse events of grade 3 or higher were reported in 29 patients (41.4%), which primarily included vasculitis, hypothyroidism, hypersensitivity reactions, and diarrhea. Conclusion: The use of camrelizumab significantly improved treatment outcomes and prognosis for patients with recurrent, metastatic, and treatment-naïve advanced cervical cancer, with significantly improved progression-free survival. Although a certain proportion of patients experienced adverse events of grade 3 or higher, the overall safety profile was acceptable. In clinical practice, immunotherapy offers a more effective treatment option for patients.

Key words: Cervical cancer, Immunotherapy, Chemotherapy, Targeted therapy, Recurrence, Metastasis, Treatment-naive, Prognosis

中图分类号:

R737.33

范素梅, 信聪伶, 朱来芳, 刘畅, 徐蕊, 周正荣, 程玺. 卡瑞利珠单抗联合化疗及靶向治疗在复发、转移及初治晚期宫颈癌中的疗效与安全性分析：一项回顾性队列研究[J]. 中国癌症杂志, 2025, 35(6): 570-577.

FAN Sumei, XIN Congling, ZHU Laifang, LIU Chang, XU Rui, ZHOU Zhengrong, CHENG Xi. Effectiveness and safety analysis of camrelizumab combined with chemotherapy and targeted therapy in patients with recurrent, metastatic, and treatment-naive advanced cervical cancer: a retrospective cohort study[J]. China Oncology, 2025, 35(6): 570-577.

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Baseline characteristics	Observation group (n=70)	Control group (n=60)	χ² value	P value
Age/year ($\bar{x}\pm s$)	50.90±9.32	53.50±11.37		0.155
Type of recurrence before treatment [n(%)]			8.34	<0.001
Distant metastasis	68 (97.1)	46 (76.7)
Pelvic metastasis	2 (2.9)	14 (23.3)
Pathological type [n(%)]			13.89	0.414
Squamous cell carcinoma	50 (71.4)	36 (60.0)
Adenocarcinoma	13 (18.6)	13 (21.7)
Adenosquamous carcinoma	3 (4.3)	3 (5.0)
Other types	4 (5.7)	8 (13.3)
Previous treatment [n(%)]			7.09	0.081
Surgery±chemoradiotherapy	38 (54.3)	24 (40.0)
Surgery	3 (4.3)	8 (13.3)
Chemoradiotherapy	13 (18.6)	19 (31.7)
Chemotherapy	1 (1.4)	0 (0.0)
Radiotherapy	1 (1.4)	0 (0.0)
Treatment-naive	14 (20.0)	9 (15.0)

Efficacy indicators	Overall (n=130)	Observation group (n=70)	Control group (n=60)	χ² value	P value
Tumor response n(%)				-	<0.001^*
CR	8 (6.2)	5 (7.1)	3 (5.0)
PR	55 (42.3)	46 (65.7)	9 (15.0)
SD	17 (13.1)	5 (7.1)	12 (20.0)
PD	50 (38.5)	14 (20.0)	36 (60.0)
ORR/%	48.5	72.9	20.0	36.140	<0.001
DCR/%	61.5	80.0	40.0	21.840	<0.001

Adverse reactions	Grade 2	Grade 3	Grade 4
Angiogenesis	1 (3.2%)	8 (25.8%)	1 (3.2%)
Hand-foot syndrome	0	0	1 (3.2%)
Hypothyroidism	0	3 (9.7%)	2 (6.4%)
Allergic	0	2 (6.4%)	0
Thrombus	0	0	1 (3.2%)
Thrombocytopenia	0	5 (16.1%)	1 (3.2%)
Anemia	0	1 (3.2%)	0
Diarrhea	0	1 (3.2%)	0
Renal insufficiency	1 (3.2%)	0	0
Immune pneumonia	0	0	1 (3.2%)
Proteinuria	0	1 (3.2%)	0
Shingles	0	1 (3.2%)	0

Variable	Patients n	Univariate analysis		Multivariate analysis
Variable	Patients n	HR (95% CI)	P value	HR (95% CI)	P value
Age/year
≤55	84	Reference
>55	46	1.192 (0.699-2.033)	0.519
Pathology type
Squamous cell carcinoma	86	Reference
Adenocarcinoma	26	1.322 (0.688-2.542)	0.403
Adenosquamous carcinoma	6	0.818 (0.197-3.407)	0.783
Other types	12	0.994 (0.420-2.357)	0.990
Initial treatment method
Chemoradiotherapy	32	Reference		Reference
Surgery±chemoradiotherapy	62	0.436 (0.246-0.773)	0.004	0.584 (0.327-1.041)	0.068
Chemotherapy	1	0.000 (0.000-Inf)^*	0.997	0.000 (0.000-Inf)	0.998
Surgery	11	0.929 (0.377-2.290)	0.874	0.935 (0.380-2.303)	0.884
Radiation therapy	1	0.000 (0.000-Inf)	0.998	0.000 (0.000-Inf)	0.998
Untreated	23	0.159 (0.055-0.464)	< 0.001	0.196 (0.067-0.576)	0.003
Type of recurrence
Distant	114	Reference		Reference
Pelvic	16	1.853 (0.980-3.505)	0.058	1.176 (0.611-2.267)	0.627
Adverse drug reactions
Yes	47	Reference
No	83	1.319 (0.756-2.303)	0.330
Carrelizumab treatment
Yes	70	Reference		Reference
No	60	4.567 (2.497-8.352)	<0.001	3.814 (2.027-7.177)	<0.001