Objective  To analyze the efficacy and safety of programmed death receptor 1 (PD-1) inhibitor combined with anlotinib as post-line therapy for patients with advanced esophageal squamous cell carcinoma (ESCC).

  Methods  We examined patients with advanced ESCC who were treated with PD-1 inhibitor combined with anlotinib until disease progression or intolerance. The primary endpoint was progression-free survival (PFS). The secondary endpoints were objective response rate (ORR) and overall survival (OS). The last follow-up was conducted on November 30, 2021.

  Results  From March 2019 to July 2021, 63 patients met the inclusion criteria and received PD-1 inhibitor combined with anlotinib at Affiliated Cancer Hospital of Zhengzhou University. The median progression-free survival (mPFS) was 7.1 months (95%CI:4.3–9.9). The ORR and disease control rate (DCR) were 14.3% and 69.8%, respectively. The median overall survival (mOS) had not yet been reached. Adverse events included fatigue (49.2%), hypothyroidism (46.0%), hypertension (38.1%), nausea and vomiting (34.9%), hand-foot syndrome (33.3%), and rash (31.7%). Grade 3 adverse reactions included bleeding and perforation (4.8%), interstitial pneumonia (3.2%), hypothyroidism (3.2%), immunocarditis (1.6%), rash (1.6%), and diarrhea (1.6%). No grade 4 adverse reactions or treatment-related deaths occurred.

  Conclusions  PD-1 inhibitor combined with anlotinib shows significant efficacy and good safety for treating ESCC that progresses after advanced chemotherapy. The therapy could also be a post-line therapy option for patients with ESCC.