Hepatic arterial infusion chemo outdoes sorafenib for advanced liver cancer

Hepatic arterial infusion chemotherapy consisting of a FOLFOX* regimen (HAIC-FO) showed superior efficacy over sorafenib in the first-line treatment of locally advanced or unresectable hepatocellular carcinoma (HCC), according to the findings of the phase III FOHAIC-1 study presented at ASCO 2021.

 

In advanced HCC, macrovascular invasion is commonly seen upon initial diagnosis, with less extrahepatic metastases. [Oncol Lett 2017;14:705-714] “[Our findings suggest that for HCC] patients with heavy intrahepatic tumour burden, HAIC-FO monotherapy might be a better strategy than sorafenib,” said Dr Ming Zhao from Sun Yat-sen University Cancer Center, Guangzhou, China.

 

In this open-label trial, 262 participants who had not received prior systemic therapy were randomized 1:1 to receive HAIC-FO** Q3W or sorafenib 400 mg BID. Macrovascular invasion rates with or without extrahepatic metastasis were similar between the HAIC-FO and sorafenib arms (85 percent vs 81 percent), as was the fraction of participants with >50 percent liver involvement (42 percent vs 39 percent). Median tumour diameters were also similar (11.7 vs 10.8 cm). [ASCO 2021, abstract 4007]

 

At data cutoff, patients receiving HAIC-FO had a longer median overall survival (OS) than those on sorafenib (13.9 vs 8.2 months; hazard ratio [HR], 0.41, 95 percent confidence interval [CI], 0.30–0.55; p<0.001).

 

OS was consistent across subgroups, most notably among participants with tumour sizes of ≤10 cm (HR, 0.22, 95 percent CI, 0.13–0.39) and those with high-risk factors*** (HR, 0.29, 95 percent CI, 0.19–0.46). The rates of HAIC-FO vs sorafenib recipients with high-risk factors were comparable (54 percent vs 45 percent).

 

OS was also significantly longer with HAIC-FO vs placebo among patients who underwent conversion therapies (median, 20.4 vs 11.5 months; HR, 0.19, 95 percent CI, 0.09–0.36) and those with high-risk factors (median, 10.8 vs 5.7 months; HR, 0.34, 95 percent CI, 0.22–0.54; p<0.001 for both).

 

Among those who had conversion therapy, 16 HAIC-FO recipients had tumour downstaging as opposed to only one in the sorafenib arm. Zhao noted that the tumour downstaging rate with HAIC-FO was “promising”. Consequently, 15 of the HAIC-FO recipients were able to receive curative and/or palliative therapies (eg, ablation surgery).

 

“[Moreover,] HAIC-FO has the advantage of rapid tumour shrinkage within a short period (median time to response 2.2 months),” noted Zhao. “[This] has never been reported in previous studies on standard systemic agents.”

 

In terms of safety and tolerability, HAIC-FO appeared to fare better than placebo, as reflected by the lower rates of grade 3/4 adverse events with the former vs the latter (20 percent vs 48 percent). The primary complication reported with HAIC-FO was acute abdominal pain during the later phase of oxaliplatin infusion (41 percent). Nonetheless, no infusion-related events led to treatment withdrawal.

 

“[Taken together,] interventional HAIC-FO therapy may be a potential first-line option for patients with advanced HCC, especially for those with severe local tumours,” concluded Zhao. The current findings support previous trials that have shown the potential of HAIC-FO in this patient setting. [Gut 2018;67:395-396; J Hepatol 2018;69:60-69]