1628P Anlotinib plus chemotherapy as first-line therapy for gastrointestinal tumor patients with unresectable liver metastasis: Preliminary results from a multi-cohort, multi-center phase II trial (ALTER-G-001)

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) and have poor prognosis. Previous trials showed anlotinib plus chemotherapy (CT) 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 CT as first-line (1L) treatment for LMs GI tumors. Previous untreated pts with unresectable LMs GI tumors received induction therapy (6 cycles, q3w) in 3 cohorts: cohort A (CRC): anlotinib (12 mg, po, qd, d1-d14), oxaliplatin (130 mg/m2, iv, d1), capecitabine (850 mg/m2, po, bid, d1-14). B (ESCC): anlotinib, cisplatin (60-750 mg/m2, iv, d1/d1-3), paclitaxel (135 mg/m2, iv, d1) or docetaxel (75 mg/m2, iv, d1). C (other GI tumors, e.g., PC, GC): anlotinib plus standard CT. Pts without PD and radical resection received anlotinib and metronomic capecitabine (500 mg, po, bid, d1-21, q3w) maintenance until PD or unacceptable toxicity. The primary endpoint was ORR (RECIST 1.1). Secondary endpoints were DoR, PFS, OS, DCR, radical resection rate for LMs and safety. As of May 8th, 2023, 74 pts were enrolled, 33 in cohort A, 3 in B and 38 in C (26 PC, 6 GC, 5 biliary tract cancer (BTC) and others), median age was 64 years (34-75), 70.3% male, 91.9% ECOG-PS 1 and 59.5% had LMs only. After induction therapy, 8 pts (5 CRC, 1 PC, 1 GC, 1 BTC) received surgical resection. Of 19 evaluable pts in cohort A, ORR and DCR were 57.9% and 100% (PR, n=11; SD, n=8, 5 SD had reduced tumor size). All 3 pts in cohort B were PR. Of 28 evaluable pts in cohort C, ORR and DCR were 39.3% and 85.7% (PR, n=11; SD, n=13, 6 SD had reduced tumor size). Of 16 evaluable PC pts, 7 had PR, 7 had SD, ORR 43.8%. The mPFS was not reached. 50 pts had TEAEs and grade 3/4 TEAEs (28.4%) mainly included neutropenia (13.5%), hypertension (6.8%) and white blood cell decreased (5.4%). Anlotinib plus chemotherapy as 1L treatment has shown promising efficacy and acceptable safety and may be a favorable option for advanced LMs GI tumors, especially for PC.