983P - Safety and efficacy of durvalumab plus hepatic artery infusion chemotherapy in HCC with severe portal vein tumor thrombosis (Vp3/4) – the DurHope study

Background

The HIMALAYA trial demonstrated that the efficacy of durvalumab (an PD-L1 inhibitor) is comparable to that of sorafenib in patients (pts) with advanced hepatocellular carcinoma (HCC), and its safety profile is more acceptable. The FOHAIC-1 study indicated that hepatic arterial infusion chemotherapy (HAIC) achieves better survival than sorafenib in advanced HCC with intrahepatic high-risk factors (i.e., Vp4 portal vein tumor thrombosis [PVTT]). This study aimed to evaluate the safety and efficacy of durvalumab plus HAIC as first-line therapy in pts with HCC with Vp3/4 PVTT.

Methods

The DurHope study was a single-arm, phase 2 trial. Eligible pts had HCC with Vp3/4 PVTT with no previous systemic treatment. Pts received HAIC of FOLFOX regimens (oxaliplatin 130 mg/m², leucovorin 200 mg/m², fluorouracil 400 mg/m², and fluorouracil 2,400 mg/m²) on day 1–3 plus durvalumab (1120 mg) intravenously on day 7 (±2) of each 21-day cycle for 8 cycles, followed by maintenance with durvalumab (1500 mg) every 28 days until disease progression, unacceptable toxicity, or death. The primary endpoint was 1-year overall survival (OS) rate. Secondary endpoints were progression-free survival (PFS), objective response rate (ORR) per RECIST v1.1, and safety.

Results

In this interim analysis, as of March 20, 2023, 19 pts who received at least one cycle of durvalumab and HAIC were included. The ORR was 47.4% (9/19) with 1 complete response and 8 partial response. The median time to response was 1.3 months (95% CI, 1.3–2.7), and the median duration of response was 5.4 months (95% CI, 3.7–5.8). The most common treatment-emergent adverse events (TEAEs) were hypoalbuminemia (18 [94.7%]), anaemia (17 [89.5%]), and neutropenia (16 [84.2%]). Grade 3/4 TEAEs occurred in 13 pts (68.4%). Two pts (10.5%) experienced grade 4 upper gastrointestinal bleeding.

Conclusions

Combination treatment with durvalumab and HAIC showed promising antitumor activity with ORR of 47.4% in HCC with Vp3/4 PVTT. Prophylactic gastrointestinal endoscope might be necessary to decrease the risk of gastrointestinal bleeding in such pts. Enrollment is ongoing and longer follow-up is needed to evaluate the survival data.

Clinical trial identification

NCT04945720.

Editorial acknowledgement

Legal entity responsible for the study

AstraZeneca.

Funding

AstraZeneca.

Disclosure

All authors have declared no conflicts of interest.