539P - Hepatic arterial infusion chemotherapy combined with sintilimab and regorafenib as adjuvant therapy for colorectal liver metastasis patients with high risk of recurrent: A single-arm, phase II study

Background

Despite hepatectomy being the cornerstone for colorectal liver metastasis (CRLM) management, the postoperative 1-year recurrence rate remains alarmingly high (∼70%). This Phase II trial assesses the efficacy and safety of an adjuvant combination therapy of hepatic arterial infusion chemotherapy (HAIC) with Sintilimab and Regorafenib in pts with high-risk CRLM.

Methods

Post-hepatectomy pts with histologically confirmed CRLM and a Clinical Risk Score (CRS) ≥2 were included in this study. HAIC -FOLFOX was administered every 4-6 weeks (2-4 cycles based on patient health status), alongside Sintilimab (200mg, iv, day1) and Regorafenib (80mg, po, days 1-21) every 3 weeks for up to 2 years. The primary endpoint was the 1-year recurrence-free survival (1y-RFS), with secondary endpoints including TTP, OS, RFS, and safety.

Results

From August 2022 to April 2024, 35 pts with a median age of 56 (range 38-71) were enrolled. 60% were male, 40% had K-RAS mutations, all presented with an ECOG 0 and Child-Pugh class A. Majority (74.3%) had the primary tumor in the left colon, and 45.7% presented with synchronous liver metastases. Prior to hepatectomy, 80% had ≥2 liver metastases, and 22.9% had the largest liver tumor diameter >5 cm. CRS scores were 2 (42.9%), 3 (34.3%), 4 (20%), and 5 (2.9%). At a median follow-up of 13.1 months (range 11.3-20.8), 32 pts underwent at least one efficacy evaluation, 9 experienced recurrence or death within 1 year. 1y-RFS exceed the hypothesis, achieving 67.8%. TTP, OS and RFS have not yet been reached. Adverse events (AEs) occurred in 60% of pts, consistent with TRAEs. Common TRAEs included hand-foot syndrome (20%), rash (17.1%), and emesis (17.1%). Grade ≥3 TRAEs were limited to rash (2.9%) and decreased platelet count (2.9%). Drug suspensions occurred in 11.4%, with 17.1% discontinuing Regorafenib due to TRAEs.

Conclusions

The adjuvant combination of HAIC, Sintilimab, and Regorafenib demonstrates feasible efficacy and an acceptable safety profile for high-risk CRLM. Further detailed analysis is warranted to confirm long-term benefits and safety of this regimen.

Clinical trial identification

NCT05753163.

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.