Anti-PD-1 Immunotherapy Improves the Efficacy of Hepatic Artery Infusion Chemotherapy in Advanced Hepatocellular Carcinoma

Abstract

Background Hepatic artery infusion chemotherapy (HAIC) and anti-programmed cell death protein-1 (PD-1) immunotherapy have shown promising outcomes in patients with advanced hepatocellular carcinoma (HCC), respectively. However, the combination of the two treatments has not been reported. In this study, we compared the efficacy of HAIC combined with anti-PD-1 immunotherapy (HAICAP) and HAIC in patients with advanced HCC. Methods Between November 2018 and December 2019, advanced HCC patients that were treated with either HAICAP or HAIC were retrospectively recruited and reviewed for eligibility. Efficacy was evaluated according to tumor response and survival. Results As a result, 229 patients were included in this study. Patients were divided into HAICAP group (n = 81) and HAIC group (n = 148) accordingly. The follow-up time ranged from 1.0 to 21.6 months, with a median of 11.0 months. The median overall survival was 18.0 months in the HAICAP group and 14.6 months in the HAIC group (p = 0.018; HR = 0.62; 95% CI 0.34–0.91). The median progression-free survival was 10.0 months in the HAICAP group and 5.6 months in the HAIC group (p = 0.006; HR = 0.65; 95% CI 0.43–0.87). The disease control rate in overall response (83% vs 66%; p = 0.006) and intrahepatic response (85% vs 74%, respectively; p = 0.045) were higher in the HAICAP group than in the HAIC group. Conclusion In comparison to HAIC, HAICAP was associated with a better treatment response and survival benefits for patients with advanced HCC.

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

“…Numerous clinical trials in patients with uHCC have shown that combination of TKIs and ICIs achieved substantial clinical efficacy, with higher ORR and better survival outcomes than monotherapy. [13][14][15][16][17][18][19][20][21][22][23][24][25][26] In 2020, the FDA approved the combination therapy of atezolizumab plus bevacizumab as a first-line treatment for advanced HCC based on the results of the IMbrave150 trial, which demonstrated an ORR of 33.2% (mRECIST) and median PFS of 6.8 months. 19 The combination therapy of LEN and pembrolizumab showed good anti-tumor activity, with an impressive ORR of 46%, median PFS of 9.3 months, and median OS of 22 months (NCT03006926).…”

“…20 The ORR of dual therapy in uHCC ranged from 13.6% to 46%. [13][14][15][16][17][18][19][20][21][22][23][24][25][26] TACE is the only guideline-recommended therapy for intermediate HCC patients and showed a high tumor response to uHCC with a tolerable safety profile. Combined therapy with different mechanisms of action may improve outcomes, 34 thus we assessed the triple therapy (LEN+PD-1+TACE) in uHCC, which achieved the highest ORR, conversion rate to liver resection, and pathological CR rate to date.…”

“…At present, most of the combination therapies are dual therapies: combinations of TKIs and ICIs, combinations of two ICIs, combinations of TKIs and TACE, combinations of ICIs and cytotoxic agent, or a combination of TKIs and hepatic arterial infusion chemotherapy. [13][14][15][16][17][18][19][20][21][22][23][24][25][26] Notably, lenvatinib (LEN, TKIs) combined with anti-PD-1 antibodies (PD-1, ICIs) exerted promising effects on uHCC, with an objective response rate (ORR) of 36-66.7% (NCT03006926, NCT03418922, and NCT03841201). However, the clinical experience of triple therapy (TKIs + ICIs + TACE) in the treatment of patients with uHCC is limited.…”

Reductions in AFP and PIVKA-II can predict the efficiency of anti-PD-1 immunotherapy in HCC patients

“…For instance, the combination of PD-1 antibody and targeted drugs can significantly improve the survival of HCC patients, and the A + T regimen has been one of the first-line treatments for advanced HCC patients [ 8 ]. Jie et al has found that PD-1 antibody plus locoregional therapy can improve the efficiency of anti-PD-1 immunotherapy [ 35 ]. Besides, anti-PD-1 therapy combined with targeted drugs and locoregional therapy can further prolong the survival of HCC patients compared with lenvatinib monotherapy [ 36 ].…”

Portal Vein Tumor Thrombosis and Hepatocellular Carcinoma – The Changing Tides

“…31,34 The combination of HAIC with RT has also been reported to significantly prolong OS and PFS better as compared to sorafenib alone among HCC with VP4 PVTT (median, 9.9 versus 5.3, and 3.9 versus 1.9 months). 121 Recently combining HAIC with TACE and Sorafenib proved to be a safe and better treatment option for patients with PVTT, 122 while addition of anti-PD-1 immunotherapy was reported to improve the efficacy of HAIC in advanced HCC 123 (Table 3).…”