Chen Jian, Yu Haijuan, Lin Yingtao, Hu Dan, Liu Li, Fan Renliang, Zou Jianping, Zang Lele, Lin Yao, Lin Rong, Chen Dezhao, Weng Xiaoying, Shen Fenfang, Wang Shaoyu, Zeng Wei, Tian Qihua, Yi Yun, Chen Yuanfeng, Miao Jinjin, Zhang Bo, Zou Yinxia, Gao Fengming, Lian Rong, Yang Lin, Sun Yang
Department of Gynecology, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou, China.
Department of Clinical Medical Research Center, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou, China.
Front Immunol. 2025 Jul 14;16:1611696. doi: 10.3389/fimmu.2025.1611696. eCollection 2025.
BACKGROUND: Immunotherapy has become a powerful clinical strategy for treating recurrent or metastatic cervical cancer (R/M CC). Cadonilimab, a novel anti-PD-1/CTLA-4 bispecific antibody, has shown substantial clinical benefits in cancer treatment. However, there is no real-world evidence of cadonilimab with a considerable sample size in R/M CC. Hence, we aim to assess the efficacy and safety of cadonilimab in R/M CC patients and explore its potential mechanism. METHODS: This retrospective real-world study examined a sample of R/M CC patients treated with cadonilimab at 13 large academic medical centers in China from July 6, 2022, to October 1, 2023. The outcomes were objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), as well as safety profiles. Additionally, the programmed cell death 1 ligand 1 (PD-L1) was detected by immunohistochemistry to confirm its predictive values. Whole exome sequencing (WES) was also performed to investigate its potential antitumor mechanisms. RESULTS: Among the 129 patients with measurable disease, the ORR was 38.8%, consisting of complete and partial responses in 8.5% and 30.2% of patients, respectively. The DCR was 72.1%. The median PFS was 12.4 months, while the median OS has not yet been reached. Subgroup analysis showed a numerical trend toward longer median PFS in patients with PD-L1 CPS ≥ 1 compared with CPS < 1 (14.0 vs. 12.8 months; P = 0.235). Moreover, combined therapy of cadonilimab and radiotherapy was identified as an independent prognostic factor for both OS and PFS. The most common grade 3 or worse adverse event was anemia (28 [20.1%]), decreased white blood cell count (24 [17.2%]), and decreased neutrophil count (20 [14.4%]). The most prevalent genetic variant was PIK3CA, highlighting the importance of the PI3K-AKT pathway in the antitumor mechanism of cadonilimab. CONCLUSIONS: Cadonilimab shows an encouraging tumor response rate, with a manageable safety profile in patients with R/M CC. Notably, cadonilimab is also effective for those with PD-L1 CPS <1, suggesting a broad range of application prospects in R/M CC. CLINICAL TRIAL REGISTRATION: https://www.clinicaltrials.gov, identifier NCT06140589.
背景：免疫疗法已成为治疗复发性或转移性宫颈癌（R/M CC）的有力临床策略。卡度尼利单抗是一种新型抗PD-1/CTLA-4双特异性抗体，在癌症治疗中已显示出显著的临床益处。然而，在R/M CC中尚无大样本量的卡度尼利单抗的真实世界证据。因此，我们旨在评估卡度尼利单抗在R/M CC患者中的疗效和安全性，并探索其潜在机制。 方法：这项回顾性真实世界研究考察了2022年7月6日至2023年10月1日在中国13家大型学术医疗中心接受卡度尼利单抗治疗的R/M CC患者样本。观察指标包括客观缓解率（ORR）、疾病控制率（DCR）、无进展生存期（PFS）、总生存期（OS）以及安全性。此外，通过免疫组织化学检测程序性细胞死亡1配体1（PD-L1）以确认其预测价值。还进行了全外显子测序（WES）以研究其潜在的抗肿瘤机制。 结果：在129例可测量疾病的患者中，ORR为38.8%，分别有8.5%和30.2%的患者达到完全缓解和部分缓解。DCR为72.1%。中位PFS为12.4个月，而中位OS尚未达到。亚组分析显示，与PD-L1 CPS＜1的患者相比，PD-L1 CPS≥1的患者中位PFS有延长的数值趋势（14.0个月对12.8个月；P = 0.235）。此外，卡度尼利单抗与放疗的联合治疗被确定为OS和PFS的独立预后因素。最常见的3级或更严重不良事件是贫血（28例[20.1%]）、白细胞计数减少（24例[17.2%]）和中性粒细胞计数减少（20例[14.4%]）。最常见的基因变异是PIK3CA，突出了PI3K-AKT通路在卡度尼利单抗抗肿瘤机制中的重要性。 结论：卡度尼利单抗在R/M CC患者中显示出令人鼓舞的肿瘤缓解率，且安全性可控。值得注意的是，卡度尼利单抗对PD-L1 CPS＜1的患者也有效，表明在R/M CC中有广泛的应用前景。 临床试验注册：https://www.clinicaltrials.gov，标识符NCT06140589。
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