Chemotherapy combined with PD-1 inhibitor immunotherapy is the standard treatment for advanced esophageal squamous cell carcinoma (ESCC), yet patient prognosis remains unsatisfactory, with a median PFS of only about 6 months and a 1-year PFS rate of only 25%. Adding anlotinib maintenance therapy on top of PD-1 inhibitor immunotherapy maintenance after chemoimmunotherapy may improve progression-free survival and overall survival. We plan to conduct a randomized, multicenter, open-label Phase II study of anlotinib combined with PD-1 inhibitor maintenance therapy versus PD-1 inhibitor monotherapy maintenance in advanced ESCC. A total of 112 patients with unresectable locally advanced, recurrent, or metastatic ESCC are planned to be enrolled. After enrollment, patients will receive either anlotinib combined with PD-1 inhibitor maintenance therapy or PD-1 inhibitor monotherapy maintenance, with a maximum treatment duration of 2 years. This study aims to evaluate the efficacy and safety of anlotinib combined with PD-1 inhibitor maintenance therapy in advanced ESCC by comparing it with the PD-1 inhibitor monotherapy maintenance group, further optimizing the comprehensive treatment model for esophageal cancer.
Pathologically confirmed esophageal squamous cell carcinoma;
Unresectable locally advanced, recurrent, or metastatic esophageal squamous cell carcinoma that has not received prior systemic therapy, or recurrence more than 6 months after completion of (neo)adjuvant/radical therapy;
Patients who have completed 4-6 cycles of PD-1 inhibitor combined with platinum-based doublet chemotherapy, who may receive local therapy if the investigator determines a benefit from local treatment, and who have not progressed after the above treatment;
Enrollment window: randomization must be performed within 42 days after completion of the last treatment (including local therapy);
Known or suspected allergy to the study drug or to any drug administered in connection with this trial;
Patients who can be cured by surgery or radiotherapy;
Endoscopic or imaging findings indicating obvious deep ulceration of the esophageal lesion; or obvious invasion of adjacent vital organs (such as the aorta or trachea) by the tumor with a very high risk of bleeding or perforation; or formation of an esophageal-tracheal fistula/esophageal-mediastinal fistula;
Presence of complete esophageal obstruction requiring interventional treatment; prior esophageal or tracheal stent placement before enrollment; or presence of factors that significantly affect the absorption of oral drugs (anlotinib), such as inability to swallow tablets, chronic diarrhea, or intestinal obstruction;
Parallel
anlotinib + PD-1 inhibitor
DrugPD-1 inhibitor, 200 mg/240 mg, intravenous infusion, d1, Q3W; Anlotinib: 10 mg, qd, oral, d1-14, Q3W; Repeated every 3 weeks, for 2 years or until disease progression or intolerable toxicity
PD-1 inhibitor
DrugPD-1 inhibitor, 200 mg/240 mg, intravenous infusion, d1, Q3W; Repeated every 3 weeks, for 2 years or until disease progression or intolerable toxicity
Progression-free survival
The time from enrollment until the first occurrence of documented disease progression or death from any cause, whichever occurs first.
Progression-free survival 2
The time from enrollment to the first occurrence of disease progression on the next line of subsequent therapy or death from any cause, whichever occurs first.
Overall survival
The time from enrollment until death from any cause.
DoR (Duration of Response)
The time from enrollment or the first documentation of objective tumor response (complete response \[CR\] or partial response \[PR\]) to the first occurrence of documented disease progression or death from any cause, whichever occurs first.
Treatment-related adverse events
Incidence of treatment-related adverse events as assessed by CTCAE v5.0.
Correlation between PD-L1 and overall survival
The correlation between pretreatment PD-L1 by immunohistochemistry and overall survival.
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Sun Yat-sen University
Lead sponsor
Sun Yat-Sen University Cancer Center
Collaborator
Jieyang People's Hospital
Collaborator
Jiangmen Central Hospital
Collaborator
Zhongshan People's Hospital, Guangdong, China
Collaborator
Guangdong Second Provincial General Hospital
Collaborator
Cancer Hospital of Guangdong Medical University
Collaborator
