Lenvatinib Combined with Anti-PD-1 Antibodies Plus Transcatheter Arterial Chemoembolization for Unresectable Hepatocellular Carcinoma: A Multicenter Retrospective Study

Abstract

Background: Lenvatinib (LEN) combined with anti-PD-1 antibodies (PD-1) exerted promising effects on unresectable hepatocellular carcinoma (uHCC). We assessed the safety and clinical efficacy of triple therapy [LEN+PD-1+transcatheter arterial chemoembolization (TACE)] in uHCC. Methods: uHCC patients with an ECOG PS score of 0-1 and Child-Pugh class A who underwent triple therapy were included. The primary endpoint was objective response rate (ORR) based on mRECIST. Secondary endpoints were conversion rate to liver resection and treatment-related adverse events. Results: Between November 2018 and December 2020, 62 uHCC patients who underwent triple therapy at four major cancer centers in China were analyzed, including 35 in BCLC-C, 21 in BCLC-B, and 6 in BCLC-A. With a median follow-up of 12.2 months (range, 7.6-33.3 months), the investigator and blinded independent central review-assessed ORR were 80.6% and 77.4%, respectively. A total of 33 patients (53.2%) reached the standard of conversion to resectable HCC and 29 patients underwent resection. The median interval between start of triple therapy and resection was 123 days (range, 55-372 days). Pathological complete response and major pathological response were observed in 16 and 24 patients, respectively. Median overall survival and progression-free survival were not reached. Treatment-related adverse events occurred in 74.2% of the patients (grade ≥3, 14.5%; grade ≥4, 4.8%). Conclusion: Combination of LEN, PD-1 and TACE showed a high rate of tumor response and convert resection in uHCC patients, with manageable toxicity.

Transarterial Chemoembolization Combined With Immune Checkpoint Inhibitors and Tyrosine Kinase Inhibitors for Unresectable Hepatocellular Carcinoma: Efficacy and Systemic Immune Response

“…In the current study, treatment-related AEs occurred in 85% of patients. The incidence of AEs was in accordance with the other triple therapy cohort (29), which reported AEs of 74.2%. AEs of higher grade (grade ≥3) were 14.5% in their cohort and 28% in our cohort.…”

“…At the third month, the ORR and DCR were 72.6% and 95.5%, respectively, and the median PFS was 11.4 months. In another cohort of 62 patients treated with TACE plus lenvatinib and anti-PD-1 therapy ( 29 ), they reported an ORR of 80.6%, and 32 (53.2%) patients successfully converted to resectable HCC; among these patients, 29 patients underwent resection, and 16 patients achieved a pathological complete response. Although comparisons between different studies should be cautious, these data indicated an encouraging efficacy of this triple therapy for uHCC.…”

The Significance of Transarterial Chemo(Embolization) Combined With Tyrosine Kinase Inhibitors and Immune Checkpoint Inhibitors for Unresectable Hepatocellular Carcinoma in the Era of Systemic Therapy: A Systematic Review

“…A total of 97 were excluded by duplicating, 1,353 by screening titles and abstracts, and another 22 more by reading the full text. Finally, 15 records were assessed to be eligible for this meta-analysis ( 21 , 25 , 30 – 42 ) ( Figure 1 ).…”

“…All of the included studies came from China, and all the studies were retrospective, three of which were multi-centered ( 25 , 30 , 34 ). The baseline characteristics in each study were depicted in Table 1 , as well as the results of quality assessment.…”

A Novel Blood Index-Based Model to Predict Hepatitis B Virus-Associated Hepatocellular Carcinoma Recurrence After Curative Hepatectomy: Guidance on Adjuvant Transcatheter Arterial Chemoembolization Choice

“…Currently, immunotherapy, especially immune-checkpoint inhibitor therapies, has been successful in treating advanced HCC (33,34). Combining locoregional therapy approaches such as TACE with immunotherapy is an interesting treatment plan, which may provide better results (35). The BIS model can divide patients into high and low recurrence risk groups, which can be used to filter patients for receiving adjuvant therapy.…”