Transarterial chemoembolization (TACE) combined with camrelizumab and apatinib versus TACE alone in the treatment of unresectable hepatocellular carcinoma eligible for embolization: A multicenter, open-label, randomized, phase 2 study (CAP-ACE).

LBA522 Background: Transarterial chemoembolization (TACE) has been established as a standard treatment for hepatocellular carcinoma (HCC) eligible for embolization. Combining immunotherapy and tyrosine kinase inhibitors (TKIs) with TACE can potentially enhance antitumor activity by activating the immune system and inhibiting tumor neovascularization. This study investigated whether the addition of camrelizumab and apatinib to TACE could bring better survival benefits. Methods: This open-label, randomized phase 2 study (NCT04559607) was conducted at 23 sites in China. Patients with unresectable HCC eligible for embolization were randomly assigned to receive either TACE combined with camrelizumab (200 mg once every 3 weeks) and apatinib (250 mg once daily; TACE-CA) or TACE alone. The stratification factors for randomization included vascular invasion (yes vs. no), prior use of TKIs (yes vs. no), and number of prior TACE (0 vs. 1-2). Prior immunotherapy was not allowed. The primary endpoint was progression-free survival (PFS) assessed by investigators according to the Response Evaluation Criteria In Cancer of the Liver (RECICL), analyzed in intention-to-treat population. Results: Between Dec 28, 2020 and Oct 29, 2023, 200 patients were randomized (100 in each group). Median age was 58.5 years (IQR, 51.5-65) and 57.0 years (IQR, 51-65.5) in the TACE-CA and TACE groups, respectively; most patients had Barcelona Clinic liver cancer (BCLC) stage B-C disease (86.0% and 86.0%). As of October 16, 2024, the median follow-up duration was 13.6 months (IQR, 8.2-20.5). Median PFS per RECICL was significantly longer in the TACE-CA group compared with the TACE group (11.0 months [95% CI, 8.8-13.8] vs. 3.1 months [95% CI, 2.0-4.1]; hazard ratio, 0.3, P<0.0001). The objective response and disease control rates were 65.0% (95% CI, 54.8-74.3) and 87.0% (95% CI, 78.8-92.9) in the TACE-CA group and 30.0% (95% CI, 21.2-40.0) and 63.0% (95% CI, 52.8-72.4) in the TACE group, respectively. Overall survival data are immature. Grade ≥3 treatment-related adverse events (TRAEs) occurred in 76.6% (72/94) of patients with TACE-CA and 24.3% (25/103) of patients with TACE. The most common grade ≥3 TRAEs were increased aspartate aminotransferase (AST; 29 [30.9%]), increased alanine aminotransferase (ALT; 23 [24.5%]), hypertension (13 [13.8%]), and decreased platelet count (11 [11.7%]) in the TACE-CA group, and increased ALT (16 [15.5%]) and increased AST (15 [14.6%]) in the TACE group. Conclusions: The addition of camrelizumab and apatinib to TACE can significantly prolong progression-free survival in patients with unresectable HCC eligible for embolization, with a manageable safety profile. Clinical trial information: NCT04559607 .