1008P - The safety and efficacy of PD-1 inhibitor (Sintilimab) combined with conventional transarterial chemoembolization (cTACE) for the initial treatment of the stage BCLC B hepatocellular carcinoma (HCC) beyond up-to-seven criteria

Background

TACE is the first choice for patients (pts) with intermediate-stage HCC. Numerous studies have demonstrated the limited survival benefit of TACE alone in pts with stage BCLC B, particularly in tumor beyond up-to-seven criteria. Single immunotherapy agent showed a certain effect for unresectable HCC pts, but still with unsatisfactory. This study was designed to explore the efficacy and safety of sintilimab plus cTACE for HCC with stage BCLC B (or stage CNLC IIa-IIb) beyond up-to-seven criteria.

Methods

This is a single-arm, phase II study(NCT04842565). Eligible HCC pts were treated cTACE and sintilimab (200mg, IV, Q3W). The first sintilimab dose was given after the first cTACE, and then every 3 weeks. The primary objectives were safety and progression-free survival (PFS). Secondary objectives included ORR assessed by both RECIST v1.1 and mRECIST v1.1, overall survival (OS), and disease control rate (DCR).

Results

From Oct 2020 to Feb 2023, 20 pts were enrolled with a median age of 62 years. All pts were BCLC stage B, and 45.0% (9/20) were CNLC IIa stage, 55.0% (11/20) were IIb stage. At median follow-up duration of 9.0 months, the ORR was 30.0%(95% CI: 14.6%-51.9%) per RECIST, and 60% (95%CI: 38.7%-78.1%) per mRECIST. The DCR was 95.0% (95% CI: 76.4%-99.1%) per both RECIST and mRECIST. Median PFS(by both RECIST and mRECIST) was 7.95 months (95% CI: 2.7-NA), and the median OS was not reached. Four pts converted to curative surgical resection. The optimal cut-off value of PLR(platelet-to-lymphocyte ratio) predicted tumor shrinkage was 100. Low PLR were associated with more tumor shrinkage. The most common TRAEs were hypothyroidism (37.5%), elevated aspartate aminotransferase (10.0%), rash(5.0%). Only one patient experienced grade 3 TRAE(myocarditis) and no treatment-related deaths were reported.

Conclusions

Combination of Sintilimab and cTACE showed promising antitumor activity and manageable toxicity in pts with HCC with BCLC stage B （CNLC stage IIa-IIb） beyond up-to-seven criteria. The PLR is promising predictor for tumor shrinkage in HCC. These strategy should be validated in a large randomized controlled trial.

Clinical trial identification

NCT04842565.

Editorial acknowledgement

Legal entity responsible for the study

Zhongshan hospital affiliated to Fudan University.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.