Molecular and Immune Correlates of Response to First-Line De-escalated Chemotherapy plus Penpulimab and Anlotinib in Advanced Cervical Cancer

作者：Qin Xu, Zhengrong Deng, Jing Liu, Yanhong Zhuo, Fei Zhu, Lele Chang, Qin Liu, Yajuan Fu, Peiwei Li, Yunyun Liu, Songhua Huang, Li Li, Xingyun Xie, Ying Chen, Yingtao Lin, Lele Zang, Meifang Ke, Li Chen, Xiaoxia Huang, Cong Wang, Yanhong Wang, Yaxin Kang, Yuqin Wang, Meijia Zhu, Huiqi Zhang, Zhixin Wang, Peidong Zhang, Dan Hu, Huaiwu Lu, Yang Sun, Shengtao Zhou · 发表于：Cancer Discovery · 年份：2025 · DOI：10.1158/2159-8290.cd-25-1315 · 被引用次数：2 · 研究领域：Cancer Immunotherapy and Biomarkers、Endometrial and Cervical Cancer Treatments、PARP inhibition in cancer therapy

The standard of care for advanced cervical cancer includes chemotherapy, antiangiogenic, and/or immune checkpoint blockade regimens. Although effective, it leads to pleiotropic side effects. Deescalation chemotherapy together with immunotargeted therapies has been proven effective and less toxic in other cancers. In this study, we conducted a multicenter, single-arm, phase II study of first-line deescalated platinum-based chemotherapy plus anlotinib and penpulimab, followed by maintenance therapy solely with anlotinib and penpulimab in patients with PD-L1-positive, persistent, recurrent, or metastatic cervical cancer. Of 32 efficacy-evaluable patients, 30 (93.8%, 95% confidence interval, 79.2%-99.2%) had an investigator-confirmed objective response. Single-nucleus RNA sequencing implied enhanced chemotaxis and proliferative activity of tumor-infiltrating T cells, and activated germinal center B cells portended optimal treatment response. Patients with a high tertiary lymphoid structure-to-tumor area ratio exhibited better survival. Our findings lay the groundwork for the feasibility of first-line de-escalated chemotherapy plus anlotinib and penpulimab in patients with metastatic, persistent, or recurrent cervical cancer. SIGNIFICANCE: We recruited 34 patients with advanced cervical cancer receiving two cycles of platinum-based chemotherapy plus anlotinib and penpulimab, followed by maintenance therapy solely with anlotinib and penpulimab, and showed safety and efficacy of thi...