Hepatic arterial infusion chemotherapy prolongs OS vs. sorafenib in HCC subset
Hepatic arterial infusion chemotherapy of FOLFOX regimens demonstrated superior efficacy and OS than sorafenib as first-line treatment of advanced hepatocellular carcinoma with a heavy intrahepatic tumor burden.
Researchers reported results of the randomized, open-label, phase 3 FOHAIC-1 trial during the virtual ASCO Annual Meeting.
“Interventional HAIC-FO [hepatic arterial infusion chemotherapy of FOLFOX regimens] might be a potential first-line option for patients with initial advanced HCC, especially for those with severe tumors,” Ming Zhao, MD, professor of oncology in the department of minimally invasive interventional radiology at Sun Yat-sen University Cancer Center, said during the presentation.
“HAIC-FO has the advantage of rapid tumor shrinkage within a short period [median time to response, 2.2 months], which has never been reported in the previous studies of standard systematic agents,” Zhao added.
FOHAIC-1 was the first randomized, head-to-head phase 3 clinical trial since 2017 to evaluate HAIC-FO vs. sorafenib (Nexavar, Bayer) as first-line treatment of advanced HCC, according to Zhao.
In the previous phase 2 FOXAI study, Zhao and study co-author Ning Lyu, MD, also of Sun Yat-sen University Cancer Center, and colleagues demonstrated that HAIC-FO had manageable toxicity and promising efficacy in advanced HCC. The FOHAIC-1 study by Zhao and Lyu differed from other phase 3 trials in that it focused on a population with a heavy intrahepatic tumor burden.
The researchers recruited 551 patients with locally advanced or unresectable HCC from May 2017 and May 2020. They randomly assigned 262 patients to HAIC-FO (n = 130) — which consisted of 130 mg/m2 oxaliplatin, 200 mg/m2 leucovorin and a bolus of 400 mg/m2 fluorouracil, followed by 2,400 mg/m2 fluorouracil administered as a continuous infusion for 46 hours every 3 weeks — or 400 mg twice-daily sorafenib (n = 132). Patients in the HAIC-FO group were recommended to receive tumor and normal tissue biopsy to search for potential genomic biomarkers that could predict response to treatment, researchers noted.
The groups had similar baseline characteristics, including median age (HAIC-FO, 54 years vs. sorafenib, 53 years), percentage of men (88.5% vs. 93.2%), presence of macrovascular invasion with or without extrahepatic metastasis (84.6% vs. 81.1%), median tumor diameter (11.7 cm vs. 10.8 cm), percentage of patients with more than 50% tumor involvement of the liver (41.5% vs. 39.4%) and percentage of patients deemed high risk (53.8% vs. 44.7%).
OS served as the primary endpoint. Secondary endpoints included PFS, intrahepatic tumor PFS, objective response rate, disease control rate and safety.
Median follow-up as of data cutoff for final OS analysis on Oct. 31, 2020, was 12.2 months (interquartile range [IQR], 9.1-17.2) for the HAIC-FO group and 9.7 months (IQR, 6.2-12.7) for the sorafenib group.
Results showed median OS of 13.9 months (95% CI, 10.6-17.2) in the HAIC-FO group vs. 8.2 months (95% CI, 7.5-9) in the sorafenib group (HR = 0.408; 95% CI, 0.301-0.552).
Sixteen patients in the HAIC-FO group (12.3%) experienced tumor downstaging, including 15 who underwent curative surgery or ablation. These patients achieved median PFS of 16.4 months, median OS of 20.8 months, a 1-year PFS rate of 93.8% and a 1-year OS rate of 93.8%.
Patients with high-risk factor also had significantly longer OS with HAIC-FO vs. sorafenib (10.8 months vs. 5.7 months; HR = 0.343; 95% CI, 0.219-0.538).
The HAIC-FO group had a higher ORR by RECIST version 1.1 (31.5% vs. 1.5%) and by modified HCC-specific RECIST (35.4% vs. 5.3%), including among those with intrahepatic disease (33.1% vs. 1.5% by RECIST 1.1; 37.7% vs. 5.3% by HCC-specific RECIST; all P < .001). Researchers reported median time to response of 9.3 weeks (range, 8-15) with HAIC-FO and median treatment duration of 18 weeks (range, 11.7-26.3).
No patient had to stop HAIC-FO therapy due to infusion-related complications, according to Zhao and Lyu. Grade 3 or grade 4 drug-related adverse events appeared more common among patients in the sorafenib vs. HAIC-FO group (48.1% vs. 20.3%). The primary complication during HAIC-FO, experienced by 40.6% of patients, was acute abdominal pain during the late phase of infusion with oxaliplatin.
Zhao said models for predicting therapeutic effects of HAIC-FO based on genomic mutations are currently being developed.
Collapse
Lyu N and Zhao M. Abstract 4007. Presented at: ASCO Annual Meeting (virtual meeting); June 4-8, 2021.