TACE + apatinib: A potential new strategy for intermediate/advanced HCC?

In patients with intermediate or advanced hepatocellular carcinoma (HCC), combining transarterial chemoembolization (TACE) with apatinib led to improvement in progression-free survival (PFS), according to a recent study from China.

“This is the first prospective, randomized, multicentre study to report significant PFS benefits with the combination of TACE and apatinib over TACE alone for intermediate and advanced HCC,” said Dr Bin Liang at the Presidential Symposium at ESMO Asia 2022.

Study participants were 196 patients with intermediate or advanced HCC (BCLC* stage B or C; 51 percent with stage C), Child-Pugh score ≤7 (class A or B), and ECOG performance status (PS) score 0–1 who had received 0–2 rounds of TACE prior to surgery. They were randomized 1:1 to receive TACE either alone or in combination with oral apatinib (500 mg QD) until loss of clinical benefit or intolerable toxicity.

The median age of patients in the TACE + apatinib and TACE-only arms was 52 and 54 years, respectively, and 90 and 82 percent, respectively, were male. A majority of patients were Child-Pugh class A (87 and 82 percent, respectively), had an ECOG PS of 0 (56 and 61 percent, respectively), and had no prior exposure to TACE (57 and 63 percent, respectively). Forty-nine and 52 percent, respectively, had hepatitis B infection as HCC aetiology.

PFS was significantly improved in the TACE + apatinib vs TACE-only arm (median 6.8 vs 3.8 months; hazard ratio, 0.53, 95 percent confidence interval, 0.36–0.80; p=0.0021). [ESMO Asia 2022, abstract 66O]

The PFS benefit was consistent across multiple subgroups analysed including sex, BCLC stage, alpha fetoprotein level, or presence of HBV infection, cirrhosis, or ascites.

The objective response rate was comparable between the TACE + apatinib and TACE-only arms (30.2 percent vs 23.9 percent; p=0.3427), as was disease control rate (70.9 percent vs 62.0 percent; p=0.2006). Five and four patients in the respective groups had complete responses, 21 and 18 partial responses, and 35 in each group stable disease. More patients in the TACE-alone than TACE + apatinib arm experienced disease progression (21.7 percent vs 10.5 percent).

Grade ≥3 treatment-related adverse events (TRAEs) were reported in 17 and 12 percent of patients in the TACE + apatinib and TACE-only arms, respectively. Pain was the most common grade ≥3 TRAE in the TACE + apatinib arm (3 percent) and vomiting, nausea, and decreased platelet count in the TACE-only arm (3 percent each). There were 14 grade ≥3 apatinib-associated TRAEs, the most common being pain (3 percent), hand-foot skin reactions, vomiting, increased aspartate aminotransferase levels, and proteinuria (2 percent each).

“TACE is a well-recognized therapy for patients with unresectable HCC. However, the long-term efficacy of TACE remains unsatisfactory,” noted Liang.

“TACE + apatinib can provide clinical benefits for patients with intermediate and advanced HCC, especially for patients with BCLC stage C HCC who require the combination of systemic therapy,” he continued.

Despite the positive findings, discussant Dr Teresa Macarulla from the Vall d´Hebrón University Hospital and Vall d´Hebrón Insitute of Oncology in Barcelona, Spain, pointed out that it was too early to name TACE + apatinib as a standard of care in this disease setting.

Dr Teresa Macarulla

Limitations included the Chinese-only and heterogenous (BCLC stage B–C without extrahepatic metastases) population. “[In addition,] PFS is still not a definitive surrogate for overall survival (OS) in HCC,” she said, highlighting the need for OS data and studies in a broader population.

The results also conflict with previous findings from the TACE 2 and SPACE trials, which showed no improvement in outcomes when sorafenib was added to TACE. [Lancet Gastroenterol Hepatol 2017;2:565-575; J Hepatol 2016;64:1090-1098]

“The positive findings of the Chinese study may be specific for apatinib, which is rarely used outside of China, or may be due to regional variation, such as the different aetiology of HCC in Chinese patients,” mentioned Dr Richard Hubner from the Christie NHS Foundation Trust, Manchester, UK, who was not affiliated with the study. [https://dailyreporter.esmo.org/esmo-asia-congress-2022/highlights/hepatocellular-carcinoma-apatinib-after-transarterial-chemoembolisation-prolongs-pfs-in-a-chinese-population?utm_source=newsletter&utm_medium=email&utm_campaign=ESMO-WW-COM-Members-Delegates-ESMOAsia22-email-newsletter-04.12.22, accessed 13 December 2022]

The initiation of apatinib after TACE, compared with the abovementioned trials where sorafenib was administered pre-TACE, may also have affected the findings, Hubner said.