Abstract CT213: Anlotinib plus chemotherapy as first-line therapy for gastrointestinal tumor patients with unresectable liver metastasis: Updated results from a multi-cohort, multi-center phase II trial ALTER-G-001-cohort C

Abstract Background Advanced gastrointestinal (GI) tumors, such as colorectal, gastric and pancreatic cancers (CRC, GC, and PC), and esophageal squamous cell carcinoma (ESCC), 20%-50% with liver metastases (LMs) have a poor prognosis. Previous trials showed that anlotinib plus chemotherapy has promising clinical activity and a tolerable safety profile for advanced CRC and ESCC, especially with LMs. In this phase II trial, we assessed the efficacy and safety of anlotinib plus chemotherapy as first-line treatment for LMs GI tumors. Methods Patients with unresectable LMs GI tumors and without previous systemic treatment would be divided into cohort A (CRC), cohort B (ESCC), and cohort C (other GI tumors, such as PC, GC, biliary tract cancer (BTC), etc.). In cohort C, patients received induction therapy: anlotinib plus standard chemotherapy. Patients without progressive disease (PD) and radical resection received anlotinib and metronomic capecitabine (500 mg, PO, BID, days 1-21, q3w) maintenance until PD or unacceptable toxicity. The primary endpoint was objective response rate (ORR) per RECIST v1.1. Secondary endpoints were duration of response (DoR), progression-free survival (PFS), overall survival (OS), disease control rate (DCR), time to response (TTR), depth of response (DpR), radical resection rate for LMs, and safety. Results As of November 13, 2023, 41 patients were enrolled in cohort C (29 PC, 6 GC, 5 BTC, and others), the median age was 64 years (34-74), 63.4% male, 92.7% ECOG-PS 1 and 56.1% had LMs only. The majority of the pancreatic cancer patients (26/29) received gemcitabine plus nab-paclitaxel chemotherapy combination with anlotinib as induction therapy. After induction therapy, 4 patients (1 PC, 2 GC, 1 BTC) received surgical resection. Of 38 evaluable patients in cohort C, 16 had partial response (PR), 17 had stable disease (SD) and 14 SD with reduced tumor size. The ORR was 42.1%, DCR was 86.8%. Of 26 evaluable pancreatic cancer patients, ORR and DCR were 42.3% (11/26) and 88.5%(23/26) respectively. 11 PRs and 10 SD- were observed with the median depth of response (DpR) of 37.6%. According to the Kaplan-Meier method, the median DoR was 4.1 (95%CI, 3.5-4.6) months and PFS was 5.8 (95%CI, 5.2-6.3) months. The median TTR was 1.7 (range, 0.8-3.5) months. 39 patients in cohort C had TEAEs and ≥ grade 3 TEAEs (53.7%) mainly included neutropenia (19.5%), white blood cell decreased (14.6%), and blood platelet decreased (9.8%). Conclusions Anlotinib plus chemotherapy as first-line treatment has shown promising efficacy and acceptable safety and maybe a favorable option for advanced LMs GI tumors, especially for pancreatic cancer. Clinical trial information: NCT05262335. Citation Format: Junwei Wu, Chenfei Zhou, Jun Yan, Zhengxiang Han, Chun Wang, Zhiquan Qin, Jinling Jiang, Chunbin Wang, Xinyu Tang, Lingjun Zhu, Jun Chen, Yong Mao, Xiaowei Wei, Chengfang Shangguan, Jun Zhang. Anlotinib plus chemotherapy as first-line therapy for gastrointestinal tumor patients with unresectable liver metastasis: Updated results from a multi-cohort, multi-center phase II trial ALTER-G-001-cohort C [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr CT213.