Conversion therapy for initially unresectable hepatocellular carcinoma using a combination of toripalimab, lenvatinib plus TACE: real-world study

Abstract

Background Combination conversion therapies afforded curative surgery chance for initially unresectable hepatocellular carcinoma (uHCC). This study aimed to evaluate the conversion rate and clinical outcomes of a first-line conversion regimen of lenvatinib combined with transarterial chemoembolization (TACE) plus immunotherapy for initial uHCC by interpreting real-world data. Methods Conversion therapy data of patients with uHCC from November 2018 to January 2021 were analysed. The regimens included triple combination therapy (t-CT: lenvatinib, TACE, plus toripalimab) and dual combination therapy (d-CT: lenvatinib plus TACE). Another study population diagnosed with hepatocellular carcinoma of macrovascular invasion disease were included as the upfront surgery cohort. Treatment responses and conversion rate were primary outcomes. Survival and adverse events were analysed. Results Fifty-one patients receiving t-CT (n = 30) and d-CT (n = 21) were enrolled. Higher overall response rates (76.7 per cent versus 47.6 per cent, P = 0.042) and disease control rates (90.0 per cent versus 57.1 per cent, P = 0.042) were observed via t-CT than d-CT. Both median overall survival and event-free survival were not reached in the t-CT cohort. A higher rate of curative conversion resection was achieved through t-CT than d-CT (50.0 per cent versus 19.0 per cent, P = 0.039). The disease-free survival of patients undergoing conversion resection in the t-CT cohort (n = 15) was higher than that in the upfront surgery cohort (n = 68, P = 0.039). Both t-CT and d-CT regimens were tolerable. Conclusions Better treatment responses and conversion rate for patients with uHCC were obtained with first-line t-CT. Neoadjuvant t-CT before surgery should be recommended for patients with macrovascular invasion.

Outcomes and prognostic factors in initially unresectable hepatocellular carcinoma treated using conversion therapy with lenvatinib and TACE plus PD-1 inhibitors

“…NLR is a prognostic factor in iuHCC for patients receiving triple-combination therapy ( 20 ). Baseline PLR and SIRI are also associated with the prognosis for HCC ( 9 , 25 , 26 ). In addition, the combination of C-reactive protein (CRP) and AFP showed a prognostic role in HCC patients receiving tyrosine kinase inhibitors (TKIs) combined with immunotherapy ( 27 , 28 ).…”

“…It provides patients with the opportunity for potential radical resection ( 2 , 8 ). About 50% of patients have been found to exhibit obvious tumor shrinkage after triple-combination therapy and offered curative conversion resection ( 9 , 10 ). In this context, early prediction of successful conversion surgery may guide surgical treatment strategies.…”

Conversion therapy for massive hepatocellular carcinoma: A case report and literature review

“…Among patients with initially unresectable HCC, 12.8%–56% successfully underwent radical surgery after conversion therapy (Table 2 ). 7 , 22 , 23 , 24 , 25 , 26 , 27 The combination of TKIs, ICIs, and local therapy notably had a higher conversion rate. 26 , 27 In the immune microenvironment of HCC, lenvatinib can affect the activity of tumor‐associated macrophages and cytotoxic T cells and promote the activation and infiltration of natural killer cells.…”

Efficacy and safety of transarterial chemoembolization combined with targeted therapy and immunotherapy versus with targeted monotherapy in unresectable hepatocellular carcinoma: A systematic review and meta-analysis

“…Ultimately, 14 articles were included in the analysis. [14][15][16][17][18][23][24][25][26][27][28][29][30][31]…”

“…Anti-PD-1 antibody, 240 mg intravenously every 3 wk Sun et al [13] China [24] China RCS ≤1 A/B C cTACE 68/148 NR Apatinib, given orally at 250 mg/d Sintilimab/Tislelizumab/ Pembrolizumab/ Camrelizumab, 200 mg intravenously, every 3 wk Yang et al [25] China RCS ≤2 A/B C cTACE 33/43 54.6/50.9 Sorafenib, 400 mg orally, twice a d Camrelizumab, Sintilimab, 200 mg intravenously, every 3 wk Zhao et al [26] China Zheng et al [27] China RCS ≤2 A/B B/C cTACE 22/29 NR Sorafenib, 400 mg orally, twice a d Nivolumab or Pembrolizumab, 3 mg/kg intravenously, every 3 wk Zhu et al [14] China (2) DCR The differences in DCR between the TACE-T-I and TACE-T groups are shown in Figure 3. The meta-analysis results indicated that the TACE-T-I group manifested a higher DCR than the TACE-T group (RR = 1.17; 95% CI: 1.09-1.26; P < .001).…”