Real-world data of cadonilimab in recurrent or metastatic cervical cancer in China: A multicentric study

Jian Chen¹Haijuan Yu¹Ying-tao Lin²Dan Hu³Liu Li¹Renliang Fan⁴Jianping Zou¹Lele Zang¹Yao Lin⁵Rong Lin⁶Dezhao Chen⁷Xiaoying Weng⁶Fenfang Shen⁶Shaoyu Wang⁵Wei Zeng⁸Qihua Tian⁹Yun Yi¹⁰Yuanfeng Chen¹¹Jinjin Miao¹²Bo Zhang¹³Yinxia Zou¹⁴Fengming Gao¹⁵Rong Lian¹⁶Lin Yang¹Yang Sun^1*

• ¹Department of Gynecology, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou, China
• ²Department of Clinical Medical Research Center, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou, China
• ³Department of Pathology, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital,, Fuzhou, China
• ⁴Department of Oncology, Fujian Medical University Affiliated Nanping First Hospital, Nanping, China
• ⁵Department of Obstetrics and Gynecology, The First Hospital Afffliated to Fujian Medical University, Fuzhou, China
• ⁶Department of Obstetrics and Gynecology,Fujian Provincial Hospital, Fuzhou, China
• ⁷Department of Obstetrics and Gynecology, Fujian Medical University Union Hospital, Fuzhou, China
• ⁸Department of Obstetrics and Gynecology, Gutian Hospital, Ningde, China
• ⁹Department of Gynecology, People's Hospital Affiliated to Fujian University of Traditional Chinese Medicine, Fuzhou, China
• ¹⁰Department of Gynecology, Jiangxi Cancer Hospital, Nanchang, China
• ¹¹Department of Gynecology，Shunde Women and Children’s Hospital (Maternity and Child Healthcare Hospital of Shunde Foshan), Guangdong Medical University, Foshan, China
• ¹²Lianyungang Donghai County People's Hospital, Lianyungang, China
• ¹³Department of Gynecology, Changsha Maternal and Child Health Hospital, Changsha, China
• ¹⁴Department of Gynecology, Pingxiang Maternal and Child Health Hospital, Pingxiang, China
• ¹⁵Department of Obstetrics and Gynecology, Huinan County People's Hospital, Huinan, China
• ¹⁶Beijing GenePlus Technology Co., Ltd., Beijing, China

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.