HAIC of FOLFOX Shows Positive Efficacy/Safety in Hepatocellular Carcinoma

Previous studies such as IMbrave150 (NCT03434379), SHARP (NCT00105443), and Asia-Pacific SHARP have found that advanced hepatocellular carcinoma (HCC) with mega liver masses and macrovascular invasion are commonly observed at first diagnosis. However, how to best treat these patients is yet to be determined. 

The FOHAIC-1 trial (NCT03164382) looked at the hepatic arterial infusion chemotherapy (HAIC) of oxaliplatin, fluorouracil/leucovorin (FOLFOX; HAIC-FO) versus sorafenib (Nexavar) in this patient population. The Chinese study had an actual enrollment of 262 participants and a primary end point of overall survival. Secondary end points included time to progression and time to intrahepatic tumor progression.

During the study, patients were randomized to receive FOLFOX via hepatic arterial infusion or sorafenib.

In an interview with Targeted Oncology™, Ming Zhao, MD, professor of oncology in the Department of Minimally Invasive Interventional Radiology at Sun Yat-Sen University Cancer Center, discussed how the efficacy of HAIC-FO for the treatment of HCC compares to sorafenib as investigated in the FOHAIC-1 clinical trial.

TARGETED ONCOLOGY: Can you give me a brief overview of the FOHAIC-1 study?

ZHAO: That topic is a hepatic arterial infusion chemotherapy of oxaliplatin plus fluorouracil versus sorafenib in advanced the HCC. We also gave this patient a biomolecular exploratory. This is a randomized phase 3 trials. We call it the FOHAIC-1 study. In China, HCC is identified with a liver mass and microvascular invasion. Many patients, including patients with extrahepatic metastases, tend to be large lumbo patients because many are just receiving the surgical resection. They relapse with extra hepatic metastases. So, in this kind of situation, the systemic therapy is most helpful for this patient. But in our study, the tumor location is in their liver, so, we just use the interventional hepatic arterial infusion.

FOHAIC-1 is the first randomized head-to-head a phase 3 study in this space. About 5 years ago, we just focused on this field. We had researched a phase 2 study and a respective study in this field. And this paper was published in 2018. In this study, we just included 262 patients. The chemotherapy of oxaliplatin plus fluorouracil groups included 130 patients and the sorafenib group included 132 patients. The sorafenib was standard therapy with 200 or 400 milligrams twice a daily. But in the hepatic arterial groups, we used oxaliplatin at 130 130 mg/m2, leucovorin 200 mg/m2, and fluorouracil 400 mg/m2. And then we did a fluorouracil infusion of 2,400 mg/m2 over 46 hours.

In this study, the primary end point was OS. Before we started the study, we assumed the OS in the sorafenib and the oxaliplatin, fluorouracil, leucovorin group and we calculated a sample.

Roughly two years ago, we finished the study. The best 9 characteristics of these patients, they are very different from the previous study. These patients tend to have more advanced HCC and a performance status of 1 or 2. A performance status of 0 is rare. So, the tumor diameter is very large. The tumor involvement lodges in 15% of the liver. They occupied 15.3% of the whole patient.

What were the results of this study?

In this study, the hepatic arterial infusion showed a greater response rate compare with sorafenib. The OS is also much longer in the hepatic arterial infusion group compared to sorafenib. We also conclude the statistical significance in the overall survival and in PFS.

In terms of safety, the grade 3/4 AEs were recorded more frequently with sorafenib than with hepatic arterial infusion. Grade 3/4 AEs occurred in only 20.3% of patients in the hepatic arterial infusion arm. The most frequent complication in the hepatic arterial infusion groups is abdominal pain. This occurred in about 14% of patients in our study. This is a main concern. But we used some drugs to alleviate pain.

In this study, we just used the genetic analysis of the hepatic atrial infusion groups. We just used the next generation sequencing to screen differentiation mutation genes. We found that 15 mutated genes acted a predictive model in our study. We found the predictive model can identify 83 patients who might benefit from the hepatic atrial infusion. We used the predictive model to predict the response.

The PFS was 14.3 months with hepatic atrial infusion compared with 6.2 months in the sorafenib group. The OS is 90 months versus 10 months in the sorafenib group. So, I think is the first mutated gene predictive model in this advanced stage.

How can this predictive biomarker test be applied to the community setting?

For every patient that come to our hospital, we just use a coin needle biopsy and we use a console to detect the results. We just used the model to analysis the results because we just separated patients into a response group and a no response group. When we have the genetic profile of both groups, then maybe we will use some statistical methods to analysis result and the find the 15 mutation genes. This is an exploration field. In the future, I think this will be valuable for practice.