Hepatic artery infusion chemotherapy (HAIC) combined with sintilimab and bevacizumab biosimilar (IBI305) for initial unresectable hepatocellular carcinoma (HCC): A prospective, single-arm phase II trial.

Abstract

4073 Background: Sintilimab plus IBI305, a bevacizumab biosimilar, showed a significant overall survival and progression-free survival benefit versus sorafenib in the first-line setting for patients with unresectable hepatocellular carcinoma. Hepatic arterial infusion chemotherapy is an intraarterial procedure that has been widely used in Asia, with high response rate. This trial was designed to assess the feasibility and efficacy of HAIC combined with sintilimab and IBI305 in advanced unresectable hepatocellular carcinoma. Methods: This is a prospective, single-arm phase II study. Patients with histologically or cytologically diagnosed or clinically confirmed hepatocellular carcinoma, China liver cancer staging (CNLC) stage IIb-IIIb, no previous systemic treatment, Child-Pugh classification A or B, Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 were eligible for inclusion. Patients received FOLOFOX-HAIC, followed by intravenous sintilimab (200 mg every 3 weeks, four cycles) and intravenous IBI305 (7.5 mg/kg every 3 weeks, three cycles). The primary endpoint was objective response rate (ORR) per mRECIST. Secondary endpoint were surgical conversion rate, pCR rate and R0 resection rate. The study is registered with Clinicaltrials.gov: NCT05029973. Results: Between May, 2021 to Sep, 2021, a total of 30 eligible patients were enrolled: median age 54.5 years (range 37-73); M:F 27:3; CNLC stage IIb/IIIa/IIIb: 3/16/11; Child-Pugh class A/B: 28/2; ECOG PS 0/1: 26/4. There were 23(76.7%) patients with hepatitis B and 5(16.7%) with hepatitis C. The median tumor size was 8.75 cm (interquartile range [IQR], 4.9-10.5), 60.0% pts present vascular invasion, and 36.7% had extrahepatic metastasis. Of 30 pts evaluable for response, 20 (66.7%; 95% CI: 47.2%-82.7%) achieved confirmed partial response, and became eligible for surgical resection. Finally, 14 of them received surgical resection and all (100%) achieved R0 resection, 3 pts completed radiofrequency ablation (RAF), 3 pts refused resection or RFA. The pCR rate in the patients completed pathological examination was 52.6% (95% CI: 28.9%-75.6%). The most common TRAEs included hypertension (23.3%), rash (16.7%), and abnormal liver function (10.0%). No grade 3-4 TRAEs were observed. Of note, in patients received surgery, 1 developed grade 1 biliary fistula, 1 developed hepatic failure and finally lead to death Conclusions: HAIC Combined With sintilimab and IBI305 resulted in a promising ORR, R0 surgical conversion rate and pCR rate with a manageable safety for initial unresectable advanced hepatocellular carcinoma. Further follow-up is ongoing. Clinical trial information: NCT05029973.

Safety and Efficacy of Drug-Eluting Bead Transarterial Chemoembolization Combined with Lenvatinib and Anti-PD-1 Antibodies for Unresectable Hepatocellular Carcinoma: A Retrospective Analysis

“…The results showed that 20 of the 30 subjects enrolled in the HAIC-S-IBI305 study were evaluated as PR according to mRECIST criteria, with an ORR of 66.7%. 37 The 29 participants enrolled in the TRIPLET study had an ORR of 70.96% and 87.10% based on RECIST v1.1 and mRECIST, respectively, and an mPFS of 10.80 months based on mRECIST. 38 A single-arm, Phase II study investigating the safety and assessing the efficacy of SBRT combined with sintilimab in patients with oligometastatic hepatocellular carcinoma was reported at the 2022 ASCO Annual Meeting.…”

Maintenance therapy with anlotinib after induction therapy with platinum-based chemotherapy for advanced non-small-cell lung cancer: A pooled analysis of 2 single-arm trials

“…Immunotherapy is a recommended choice of maintenance therapy. [1,2] Durvalumab was the first immune checkpoint inhibitor to demonstrate a positive impact on mPFS as a potential maintenance therapy in surgery-ineligible NSCLC, but OS data remained to be determined. [27] Pembrolizumab could prolong the mOS to 15.9 months when maintained for 35 cycles in patients with squamous NSCLC with PD-L1 expression ≥ 1% who received pembrolizumab plus chemotherapy as first-line treatment.…”

“…Due to the unavailability of effective combined immunotherapy and the concerns over the safety profile of induction chemotherapy, treatment options remain constrained for patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) lacking sensitive gene mutations. [1][2][3][4][5][6] Within this therapeutic landscape, maintenance therapy has emerged as a strategy to enhance prognosis in patients with advanced NSCLC following chemotherapy. [7][8][9][10][11][12] Anlotinib, a novel, orally administered tyrosine kinase inhibitor (TKI), targets a spectrum of receptor tyrosine kinases (RTKs), including vascular endothelial growth factor receptor (VEGFR), fibroblast growth factor receptor (FGFR), platelet-derived growth factor receptor (PDGFR), and c-kit, thereby inhibiting tumor angiogenesis and growth.…”

Immunosuppressive tumor microenvironment and immunotherapy of hepatocellular carcinoma: current status and prospectives

“…However, recent advances in immunotherapy have led to a re-evaluation of the value of systemic therapy in the conversion therapy setting. A series of phase II and phase III trials have evaluated the feasibility and effectiveness of ICIs and their combinations for conversion therapy [ 151 – 153 ] (NCT05056337, NCT05738616). However, the expected value of conversion therapy in terms of improving survival is primarily based on small-sample cohort and retrospective studies, and further evidence is still needed to validate and optimize the conversion therapy strategy.…”