150P - 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

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 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 August 14, 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. After induction therapy, 4 patients (1 PC, 2 GC, 1 BTC) received surgical resection. Of 36 evaluable patients in cohort C, ORR and DCR were 44.4% and 86.1% (PR, n=16; SD, n=15, 12 SD had reduced tumor size). Of 24 evaluable pancreatic cancer patients, 11 had PR, 10 had SD, ORR and DCR were 45.8% and 87.5%. According to the Kaplan-Meier method, the median DoR was 4.1 months (95%CI, 3.8-4.3) and the median PFS was 5.5 months (95%CI, 4.8-6.2). 34 patients in cohort C had TEAEs and ≥ grade 3 TEAEs (43.9%) mainly included neutropenia (19.5%), white blood cell decreased (12.2%), 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 identification

NCT05262335.

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.