A prospective single-arm phase II study of blank-microsphere transarterial chemoembolization (bTACE) plus lenvatinib (LEN) and sequential microwave ablation (MWA) in patients with large hepatocellular carcinoma (L-HCC, ≥ 7 cm): The Talem trial.

Abstract

567 Background: Blank-microsphere transarterial chemoembolization (bTACE) has been demonstrated to have great efficacy, low toxicities and few adverse events. We report results of efficacy, safety and immunomodulatory effects from a phase II study of bTACE plus low-dose Lenvatinib (LD-LEN) and sequential microwave ablation (MWA) in patients with large hepatocellular carcinoma (L-HCC, ≥ 7 cm). Methods: Patients with large HCC with tumor number ≤ 3 and tumor diameter ≥ 7 cm (BCLC stage A/B) were treated with bTACE plus LD-LEN (4-8mg/day) and sequential MWA. bTACE was performed using blank microspheres and low-dose chemotherapeutic agents. Peripheral blood mononuclear cells (PBMC) were isolated before and after b-TACE plus LD-LEN for the evaluation of immunomodulatory effects. The primary endpoint was objective response rate (ORR) per modified-RECIST (mRECIST) criteria. Secondary endpoints included progression free survival (PFS), overall survival (OS), down-staging rate (DSR), complications and adverse events (AEs). Results: From November 2019 to March 2022, a total of 46 patients were enrolled in the study. The ORR per mRECIST was 93.02% (CR, n=26; PR, n=14) and DSR was 83.7 (36/43). Eight patients reached CR without MWA. The 1-year and 2-year OS rates were 89.4% and 67.5%, respectively. The 1-year and 2-year PFS rates were 57.8% and 34.8%, respectively. The median PFS were 16.7 months (95% CI, 8.6-not reached). The majority of the AEs observed were grade 1-2 (n = 21, 48.8%) and no treatment related death was observed. PBMC samples from 18 patients undergoing bTACE plus LD-LEN were investigated. Among myeloid cell populations, we observed a marked decline after treatment in CD11b+CD33+HLA-DR- MDSCs ( p <0.005). Increased numbers of activated CXCR5+CD8+ and CXCR5+CD4+ T cells were found after treatment ( p < 0.005), exerting anti-tumor immunity. Conclusions: From November 2019 to March 2022, a total of 46 patients were enrolled in the study. The ORR per mRECIST was 93.02% (CR, n=26; PR, n=14) and DSR was 83.7 (36/43). Eight patients reached CR without MWA. The 1-year and 2-year OS rates were 89.4% and 67.5%, respectively. The 1-year and 2-year PFS rates were 57.8% and 34.8%, respectively. The median PFS were 16.7 months (95% CI, 8.6-not reached). The majority of the AEs observed were grade 1-2 (n = 21, 48.8%) and no treatment related death was observed. PBMC samples from 18 patients undergoing bTACE plus LD-LEN were investigated. Among myeloid cell populations, we observed a marked decline after treatment in CD11b+CD33+HLA-DR- MDSCs ( p <0.005). Increased numbers of activated CXCR5+CD8+ and CXCR5+CD4+ T cells were found after treatment ( p < 0.005), exerting anti-tumor immunity. Clinical trial information: NCT05555316 .