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

e16304 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 30, 2023, 44 patients were enrolled in cohort C (32 PC, 6 GC, 5 BTC, and others), the median age was 63.5 years (34-74), 65.9% male, 93.2% ECOG-PS 1 and 56.8% had LMs only. The majority of the pancreatic cancer patients (90.6%) 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 37 evaluable patients in cohort C, 14 had partial response (PR), 18 had stable disease (SD) and 15 SD with reduced tumor size. The confirmed ORR was 37.8%, DCR was 86.5%. Of 25 evaluable pancreatic cancer patients, confirmed ORR and DCR were 36% (9/25) and 88% (22/25) respectively. In patients with pancreatic cancer, all PRs with DpR ≥30% and DpR ≥50% were 6 (66.7%). According to the Kaplan-Meier method, the median DoR was 4.6 (95%CI, 2.89-NE) months and PFS was 5.8 (95%CI, 4.1-6.0) months. The median TTR was 1.6 (range, 1.2-3.5) months. 36 patients in cohort C had TRAEs and ≥ grade 3 TRAEs (45.5%) mainly included hypertension (11.4%), neutropenia (9.1%), and blood platelet decreased (9.1%). 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 .