A phase II study of sintilimab plus anlotinib for Chinese patients (pts) with persistent, recurrent or metastatic cervical cancer (CC)

Objectives: There are limited effective therapies for CC pts who have previously received multiple lines of chemotherapy. The combination of immune checkpoint inhibitors (ICIs) plus angiogenesis inhibitors has demonstrated significant anti-tumor activity in certain cancer. The goal of this study was to evaluate the efficacy and safety of sintilimab (a human programmed death-1 ICI) plus anlotinib (a multi-target tyrosine kinase inhibitor, inhibiting tumor angiogenesis and proliferative signaling) in persistent, recurrent or metastatic CC pts. Methods: Patients who have received at least once platinum-based systemic chemotherapy, recurrence or metastasis advanced cervical cancer (including squamous cell carcinoma, adenocarcinoma or adenosquamous carcinoma), more than 1% PD-L1 expression, ECOG 0-1 were considered eligible for enrollment. Sintilimab was administered intravenously (200mg once every 3weeks), and anlotinib was taken orally (10mg mg qd, d1-14, 21 days per cycle). The treatment was continued until disease progression, death or intolerant toxicity. The primary endpoint was objective response rate (ORR) and the secondary endpoints included disease control rate (DCR), progression-free survival (PFS), overall survival (OS) and safety. Results: From September 2019 to August 2020, 25 patients with FIGO stage I (8%), II (36%), III (44%), IV (4%) and undiagnosed (8%) were enrolled with a median age of 52 years old (range: 36-67). Among these patients, 17 patients were evaluable. The therapeutic evaluation showed the incidence of complete response, partial response, stable disease and progression disease was 11.8%, 58.8%, 29.4% and 0% respectively, yielding the ORR of 70.6% (95% CI: 44.0%-89.7%) and the DCR of 100% (95% CI: 80.5%-100.00%). The median PFS was not reached. Most of the occurring adverse events were grade 1 or 2, and >10% Grade 1 AEs included hyperlipemia (40.0%), hypothyroidism (20.0%), hypertension (16.0%), >10% Grade 2 AEs included hand-foot syndrome (12.0%). Intolerance was only observed in 1 patient. Conclusions: Sintilimab plus anlotinib showed a promising efficacy with a favorable toxicity profile for patients with persistent, recurrent or metastatic cervical cancer. We will report more data in the future.