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

Abstract

112 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). The prognosis of CRC with unresectable LMs is poor, with a 5-year survival rate of less than 5%. 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, etc.). In cohort A, CRC patients received induction therapy (6 cycles, q3w): anlotinib (12 mg, PO, QD, days 1-14), oxaliplatin (130 mg/m2, IV, day 1), capecitabine (850 mg/m2, PO, BID, days 1-14). Patients without 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 ORR (RECIST 1.1). Secondary endpoints were DoR, PFS, OS, DCR, radical resection rate for LMs, and safety. Results: As of September 14, 2023, 45 patients were enrolled in cohort A, the median age was 67 years (35-75), 66.7% male, 91.1% ECOG-PS 1 and 60% had LMs only. After induction therapy, 8 patients received surgical resection. Currently, 13 patients are receiving induction therapy and 10 are undergoing maintenance therapy, with a maximum duration of treatment (DOT) of 13.7 months. Of 39 evaluable patients in cohort A, ORR and DCR were 48.7% and 97.4% (PR, n=19; SD, n=19, 16 SD had reduced tumor size). The median PFS was not reached. 36 patients had TEAEs and ≥ grade 3 TEAEs (33.3%) mainly included neutropenia (11.1%), hypertension (6.7%), and white blood cell decreased (6.7%). Conclusions: Anlotinib plus chemotherapy as first-line treatment has shown promising efficacy and acceptable safety and maybe a favorable option for advanced LMs CRC tumors. Clinical trial information: NCT05262335 .