Molecular and immune correlates of response to first-line de-escalated chemotherapy plus penpulimab and anlotinib in advanced cervical cancer

Abstract Standard of care for advanced cervical cancer includes chemotherapy, anti-angiogenic and/or immune checkpoint blockade regimens. Although effective, it leads to pleiotropic side effects. De-escalation chemotherapy together with immunotargeted therapies have been proven effective and less toxic in other cancers. Here, we conducted a multicenter, single-arm, phase 2 study of first-line de-escalated platinum-based chemotherapy plus anlotinib and penpulimab, followed by maintenance therapy solely with anlotinib and penpulimab in PD-L1 positive, persistent, recurrent or metastatic cervical cancer patients. Of 32 efficacy evaluable patients, 30 (93.8%, 95% CI: 79.2% to 99.2%) had an investigators-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 TLS-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 metastatic, persistent, or recurrent cervical cancer patients.