Sintilimab and Anlotinib Combined With Chemotherapy in Neoadjuvant Treatment of Resectable Esophageal Cancer

A Prospective Single-center, Single-arm, Open-label Study of Sintilimab and Anlotinib Combined With Chemotherapy in Neoadjuvant Treatment of Resectable Esophageal Cancer

The study focused on patients with T2-4NxM0 resectable esophageal carcinoma. Neoadjuvant treatment involved administering anlotinib (10 mg orally, once a day, 2 weeks on and 1 week off) for anti-angiogenesis and sintilimab (200 mg) and chemotherapyfor three cycles. Surgical treatment was performed 4-6 weeks after the last chemotherapy cycle was completed. The primary endpoints assessed were pathological complete response (pCR) rate and safety.

Study Overview

• Status: Completed
• Conditions: Sintilimab and Anlotinib in Combination With Chemotherapy
• Intervention / Treatment: Drug: Sintilimab and anlotinib in combination with chemotherapy

Detailed Description

The study was conducted from April 2021 to April 2022 at our hospital and was approved by the Ethics Committee of Tangdu Hospital. The inclusion criteria were as follows: patients aged 18-75 years with a histopathologic diagnosis of esophageal cancer staged according to the AJCC eighth edition as T1-4N1-3M0. If patients were staged as T2N0M0, the esophageal lesions had to be ≥5 cm. Before enrollment, all patients underwent various examinations, including cardiac color ultrasound (left ventricular ejection fraction of at least 50%), pulmonary function (forced expiratory volume-1 [FEV1] ≥1.5 L), enhanced chest computed tomography (CT), abdominal color ultrasound, cervical lymph node color ultrasound and other necessary laboratory tests (such as blood routine, liver and kidney function, electrolytes, and cortisol rhythm) to exclude treatment and surgical contraindications and ensure suitability for ICIs treatment.

The exclusion criteria were as follows: Patients unable to tolerate surgery, those with refractory hypertension and proteinuria, those who had previously received other treatments, and those who were not suitable candidates for ICIs (due to conditions such as hepatitis B with viral quantification >2000 IU, systemic lupus erythematosus, and xerosis).

Treatment regimen:

Patients were administered preoperatively with sintilimab (200 mg, Day 1) and anlotinib (10 mg, orally, once daily, 2 weeks on and 1 week off) in combination with chemotherapy (albumin paclitaxel 130 mg/m2, Days 1 and 8 + nedaplatin 80 mg/m2, Day 1) for three cycles of neoadjuvant therapy. Surgical intervention (either Mckeown or Ivor Lewis approach) was performed 4-6 weeks after completing the last treatment cycle of neoadjuvant therapy. After the 4th week after surgery, patients received maintenance therapy with sintilimab (200 mg, Q3W) for 1 year. If any adverse reactions of grade 3 or higher occurred during the treatment, the dose of chemotherapeutic drugs was reduced by 25% until the patient's condition recovered to grade 1 or returned to normal, and the subsequent treatment cycle was continued. In case of grade 3 or higher hypertension or proteinuria, the dose of anlotinib was reduced to 8 mg. It was discontinued if the condition could not recover to grade 1-2 after symptomatic treatment.

• Study Type: Interventional
• Enrollment (Actual): 17
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Xi'an, China, 710038
    • Tangdu Hospital, the Air Force Military University
  • Shanxi
    • Xi'an, Shanxi, China, 710038
      • Hongtao Duan

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria

• patients aged 18-75 years with a histopathologic diagnosis of esophageal cancer staged according to the AJCC eighth edition as T1-4N1-3M0. If patients were staged as T2N0M0, the esophageal lesions had to be ≥5 cm.
• Before enrollment, all patients underwent various examinations, including cardiac color ultrasound (left ventricular ejection fraction of at least 50%), pulmonary function (forced expiratory volume-1 [FEV1] ≥1.5 L), enhanced chest computed tomography (CT), abdominal color ultrasound, cervical lymph node color ultrasound ▪ other necessary laboratory tests (such as blood routine, liver and kidney function, electrolytes, and cortisol rhythm) to exclude treatment and surgical ontraindications and ensure suitability for ICIs treatment.

Exclusion Criteria:

• Patients unable to tolerate surgery
• those with refractory hypertension and proteinuria
• those who had previously received other treatments
• those who were not suitable candidates for ICIs (due to conditions such as hepatitis B with viral quantification >2000 IU, systemic lupus erythematosus, and xerosis).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: anlotinib for anti-angiogenesis and sintilimab and chemotherapy; Neoadjuvant treatment involved administering anlotinib (10 mg orally, once a day, 2 weeks on and 1 week off) for anti-angiogenesis and sintilimab (200 mg) and chemotherapyfor three cycles.

Drug: Sintilimab and anlotinib in combination with chemotherapy; Neoadjuvant treatment involved administering anlotinib (10 mg orally, once a day, 2 weeks on and 1 week off) for anti-angiogenesis and sintilimab (200 mg) and chemotherapyfor three cycles. Surgical treatment was performed 4-6 weeks after the last chemotherapy cycle was completed. The primary endpoints assessed were pathological complete response (pCR) rate and safety.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Primary Endpoints: pCR	PCR: This was assessed by examining the postoperative pathological tissue for the absence of tumor cells in the primary tumor and lymph nodes.	up to 24 months

Collaborators and Investigators

• Sponsor: Tang-Du Hospital

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2021
• Primary Completion (Actual): April 1, 2022
• Study Completion (Actual): April 1, 2022

Study Registration Dates

• First Submitted: August 17, 2023
• First Submitted That Met QC Criteria: August 27, 2023
• First Posted (Actual): August 29, 2023

Study Record Updates

• Last Update Posted (Actual): August 29, 2023
• Last Update Submitted That Met QC Criteria: August 27, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Keywords: esophageal cancer; neoadjuvant; efficiency
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Head and Neck Neoplasms; Esophageal Diseases; Esophageal Neoplasms
• Other Study ID Numbers: k202204-02

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: If the clinical study obtains positive results, it will further expand the study

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No