A Retrospective Analysis of Conversion Therapy with Lenvatinib, Sintilimab, and Arterially-Directed Therapy in Patients with Initially Unresectable Hepatocellular Carcinoma

Abstract

Purpose The purpose of this study was to investigate the triple-combination therapy of lenvatinib plus sintilimab plus arterially-directed therapy as a conversion therapy for initially unresectable hepatocellular carcinoma (HCC). Patients and Methods We retrospectively analyzed data from all HCC patients who underwent lenvatinib plus sintilimab plus arterially-directed therapy at Tianjin Medical University Cancer Hospital between December 2018 and October 2020. Of 98 enrolled patients, 37 patients were classified as potentially resectable. We compared the potentially resectable population (PRP) with the non-potentially resectable population (NPRP). The primary study endpoint was conversion rate, and secondary endpoints included progression-free survival (PFS), overall survival (OS), objective response rate (ORR), disease control rate (DCR), and safety. Results The baseline characteristics were comparable between populations except for a higher proportion of patients with extrahepatic metastases in the NPRP versus PRP (23/61 [37.7%] vs 3/37 [8.1%], respectively; p=0.003). For PRP, the ORR was 67.6% based on RECIST v1.1 (75.7% based on mRECIST), conversion rate was 40.5% (15/37). Of the 15 patients who underwent surgical resection, three achieved complete pathological remission. The median follow-up for all patients was 28 months (range: 2–47). For NPRP, the ORR was 22.9% based on RECIST v1.1 (31.1% based on mRECIST), The median PFS for PRP was significantly longer than that of NPRP (25 vs 13 months, p = 0.0025). The median OS for PRP was significantly longer than that of NPRP (not reached VS 21 months, p=0.014). Hypertension was the most common grade ≥3 adverse reaction in both PRP and NPRP. No new safety signals were observed for any of the treatments. Conclusion The triple-combination therapy of lenvatinib plus sintilimab plus arterially-directed therapy can convert potentially unresectable HCC into resectable disease and improve long-term survival.

Hepatectomy After Conversion Therapy with Hepatic Arterial Infusion Chemotherapy, Tyrosine Kinase Inhibitors and Anti-PD-1 Antibodies for Initially Unresectable Hepatocellular Carcinoma

“… 16 Furthermore, HAIC, TKIs, and anti-PD-1 antibodies have a synergistic effect on the antitumor activity. 23 These theories and the results of these studies support the application of HAIC combined with TKIs and anti-PD-1 antibodies for the treatment of HCC. At our center, this combination therapy has been widely used as a treatment modality for patients with advanced HCC.…”

“…There is a discrepancy between radiological and pathological characteristics. 23,25 The pathological characteristics could help clinicians accurately evaluate the efficacy of combination therapy based on the proportion of tumor necrosis and develop appropriate postoperative treatment strategies for patients. We analyzed the factors influencing survival after surgical resection and obtained intriguing results.…”

Lenvatinib‑based treatment regimens in conversion therapy of unresectable hepatocellular carcinoma: A systematic review and meta‑analysis

“…Among the nine studies that used TACE, two utilized drug-eluting bead TACE ( 39 , 49 ). In addition, three studies implementing HAIC used the FOLFOX regimen [oxaliplatin 85 mg/m 2 ; leucovorin 400 mg/m 2 ; 5-fluorouracil bolus (400 mg/m 2 ) on day 1 and 5-fluorouracil infusion (2,400 mg/m 2 ) for 46 h; every 3 weeks] ( 24 , 47 , 48 ).…”

Clinical Complete Response After Conversion Therapy for Unresectable Hepatocellular Carcinoma: Is Salvage Hepatectomy Necessary?

“…Therefore, Currently, there are various conversion therapy regimens for uHCC, including atezolizumab plus bevacizumab, lenvatinib, sorafenib, TACE, and transarterial radioembolization. [8][9][10][11][12][13][21][22][23][24][25][26][27] With the development of systemic therapy, there are more studies reporting patients with HCC that achieve CR. In randomized controlled trials, the rate of CR after systemic therapy ranges from 1-12.5% per modified Response Evaluation Criteria in Solid Tumors (1% for sintilimab plus bevacizumab, 28 2% for lenvatinib, 29 5% for lenvatinib plus pembrolizumab, 30 8.9% for camrelizumab plus apatinib, 31 and 12.5% for atezolizumab plus bevacizumab 32 ).…”