A recent study presented by Ming Shi, MD, PhD and colleagues at ESMO Virtual Congress 2020 found that hepatic arterial infusion chemotherapy (HAIC) with oxaliplatin, fluorouracil, and leucovorin (FOLFOX) yield more effective results in patients with unresectable hepatocellular carcinoma (HCC) compared with transarterial chemoembolization (TACE). In an interview with i3 Health, Dr. Shi shares insights about the significance of these results, as well as the future of treatment for HCC, and advice for community oncologists on HCC management.
What are the most challenging aspects of treating patients with unresectable HCC?
Ming Shi, MD, PhD: Transarterial chemoembolization (TACE) is the current standard of care for patients with unresectable HCC, with a median overall survival of about 30 months for small (less than 5 cm in diameter) HCC. However, the management of large (more than 7 cm) unresectable HCC is controversial. Though tumor size is not included in most current staging systems of HCC, many previous studies had demonstrated that outcomes of TACE on large HCC were significantly worse than smaller HCC. It is not only because of higher tumor burden and less liver parenchyma but also that large HCCs commonly have plenty of collateral arteries from the right kidney, colon, stomach, phrenic, internal thoracic, and intercostal arteries; it is difficult to perform completely embolization.
Therefore, we proposed that that hepatic arterial infusion chemotherapy (HAIC) of oxaliplatin, fluorouracil, and leucovorin (FOLFOX) might be a better first-line treatment than TACE in patients with large unresectable HCC.
Can you comment on the significance of your study's findings?
Dr. Shi: This study compared HAIC with TACE for large unresectable HCC without vascular invasion or extrahepatic metastasis. The study found that HAIC with FOLFOX significantly improved overall survival (23.1 vs 16.07 months), progression-free survival (9.63 vs 5.4 months), surgical resection rate (24% vs 12%), and objective response rate (45.9% vs 15.9%) compared with TACE in patients with unresectable HCC. In addition, HAIC with FOLFOX showed less serious adverse events than TACE. In summary, HAIC appears to have efficacy and safety superior to TACE as first-line treatment for large unresectable HCC.
What are the unmet needs that still exist in this patient population?
Dr. Shi: The unmet needs that still exist in this patient population are the second-line treatment for patients who received first-line HAIC with FOLFOX. Though HAIC and FOLFOX could yield a high treatment response rate, tumor progression would be observed in half of patients within 10 months. The most common reason might be that the tumors developed resistance to chemotherapy. Therefore, effective second-line treatment is needed for these patients. In this study, 26% of patients in the HAIC group received subsequent TACE. First-line HAIC combined with second-line TACE may be a promising treatment for patients with large HCC. However, some scholars believe systemic treatment (such as atezolizumab plus bevacizumab) might be a better choice than locoregional treatment. More studies are needed to clarify effective and safe second-line treatment for these patients.
How do you see the treatment landscape evolving in the coming years?
Dr. Shi: Recently, immune checkpoint inhibitor and new tyrosine kinase inhibitors demonstrated antitumor activity and safety in unresectable HCC. I think that combination therapy will be evolving in the coming years, especially the combination of locoregional treatment and systemic treatment. In an ongoing phase II study, we are evaluating the combination of HAIC of FOLFOX, programmed death-1 (PD1) antibody, and lenvatinib. The preliminary data about safety and efficacy is exciting.
Do you have any advice for community oncologists who treat this patient population?
Dr. Shi: We now have high quality evidence from this phase 3 trial for a significant improvement in overall survival for patients treated with HAIC, and HAIC should be considered as the first-line treatment for patients with large HCC. To treat this patient population, a multidisciplinary team including oncologists, radiologists, and surgeons is necessary.
About Dr. Shi
Ming Shi, MD, PhD is a Professor at the Department of Liver Surgery, Sun Yat-sen University Cancer Center, China. Dr. Shi's research interests include mechanisms of chemotherapy resistance in HCC, and the treatments for HCC, including surgical treatment, hepatic artery infusion chemotherapy, transarterial chemoembolization, and systemic treatments.
For More Information
Shi M, Li Q, He M & Guo R (2020). Hepatic arterial infusion chemotherapy (HAIC) with oxaliplatin, fluorouracil, and leucovorin (FOLFOX) versus transarterial chemoembolization (TACE) for unresectable hepatocellular carcinoma (HCC): a randomized phase III trial.Ann Oncol, 31(suppl_4):S629-S644. Abstract 9810. DOI:10.1016/annonc/annonc278
Transcript edited for clarity. Any views expressed above are the speaker's own and do not necessarily reflect those of i3 Health.