Anlotinib plus TQB2450 as adjuvant therapy in patients with esophageal squamous cell carcinoma: A phase II study (ALTER-E005).

Abstract

347 Background: There is currently a limited range of therapeutic options available for postoperative patients (pts) with esophageal squamous cell carcinoma (ESCC), emphasizing the urgent requirement to investigate more efficient and safer postoperative treatment regimens for resectable ESCC. TQB2450, a novel PD-L1 blockade, has shown promising activity when combined with anlotinib, an antiangiogenic agent, in the treatment of various tumors, including advanced ESCC,1 and biliary tract cancer.2 The ALTER-E005 study aimed to evaluate the efficacy and safety of combining anlotinib with TQB2450 as adjuvant therapy in pts with ESCC. Methods: This was a single-arm, multi-center phase II clinical trial. 30 pts (≥18 years) with histologically confirmed T1-2N1-3M0 or T3-4NanyM0 ESCC who had undergone radical (R0) resection with no recurrence 6 to 12 weeks after surgery and ECOG PS ≤ 1 would been rolled. Enrolled pts received oral anlotinib 12 mg on days 1-14 and intravenous TQB2450 1200 mg on day 1every 3 weeks for up to 16 cycles, until disease recurrence. The primary endpoint was disease recurrence free (DFS). The secondary endpoints included safety, 1-year DFS rate, 3-year DFS rate, 1-year overall survival (OS) rate, and 3-year OS rate. Results: Between August 18, 2022, and August 25, 2023, a total of 12 patients were enrolled. Out of the 12 surgically resected cases of ESCC, 11 (91.7%) had an ECOG score of 1, 10 (83.3%) were male, and 6 (50%) were under the age of 65. According to the eighth edition of the AJCC Cancer Staging Manual, 7 (58.3%) were classified as stage II, and 5 (41.7%) were classified as stage III. As of the data cut-off date (August 25, 2023), the median follow-up time was 5.1 months (95% CI: 3.4-6.8). 2 pts experienced disease recurrence, and the median duration of DFS has not yet been reached. Currently, 9 pts are still undergoing therapy, with treatment durations ranging from 0.3 months to 9.6 months. 2 pts discontinued therapy due to adverse events (AE), which subsequently improved after treatment. One patient experienced immune-related myocarditis, while the other patient had mouth ulcers and hand-foot syndrome. Additionally, one patient voluntarily withdrew from the study. Out of the total 12 patients, 3 (25%) experienced grade 3 treatment-emergent adverse events (TEAEs). There was no grade 4 or higher TEAEs reported. The grade 3 TEAEs included hand-foot syndrome (16.7%), abnormal liver function (8.3%), and immune-related hepatitis (8.3%). Conclusions: The study demonstrated the preliminary efficacy and safety of combining anlotinib with TQB2450 as adjuvant therapy in patients with ESCC who had undergone radical (R0) resection and showed no recurrence 6 to 12 weeks after surgery. 1. Zhi-Ye Zhang, et al. poster 4041: ASCO 2023. 2. Zhou J, et al. Hepatology 2022. Clinical trial information: NCT05252078 .