Clinical trials of combined LEN and anti-PD-1 antibodies in advanced HCC have shown promising anti-tumor effects. Although responses of both intra- and extra-hepatic tumors are typically evaluated to assess efficacy of a systemic therapy in HCC, the responses of tumors in different sites or organs can be very heterogeneous.
A retrospective analysis of patients with advanced, unresectable HCC who received 1L LEN (8 mg/d regardless of bodyweight) plus anti-PD-1 antibodies either q2wk (nivolumab or camrelizumab) or q3wk (pembrolizumab, sintilimab or toripalimab). Patients who completed ≥1 efficacy and safety assessment were eligible for inclusion. Overall objective response rate (ORR) and organ-specific response rate (OSRR) were assessed using RECIST 1.1 and mRECIST. All evaluations were repeated by an independent imaging reviewer.
From Oct 2018 to Mar 2020, 59 patients were assessable for efficacy (median age: 54.3 years; 91.5% males). Among these patients, 2 (3.4%) were BCLC stage A, 11 (18.6%) were BCLC stage B, and 46 (78.0%) were BCLC stage C (including 30 with macroscopic vascular invasion, [China Liver Cancer [CNLC] stage IIIa] and 16 with extrahepatic metastasis or combined with macroscopic vascular invasion [CNLC stage IIIb]). The overall ORR evaluated using RECIST 1.1 and mRECIST was 32.2% and 57.6% according to investigator review, and 33.9% and 50.8% according to independent imaging review, respectively. OSRR was higher in macrovascular tumor thrombi (MVTT, including portal vein and hepatic veins) versus other sites (Table). Five patients with MVTT were successfully converted to liver resection because of downstaging via significant response in MVTT.
Objective response rate, % RECIST v1.1 (investigator) RECIST v1.1 (independent imaging review) Overall (n=59) 32.2 33.9 Organ-specific Liver (n=57) 33.0 32.0 Macrovascular tumor thrombi (n=33) 57.5 51.5 Lung (n=7) 37.5 37.5 Lymph node (n=6) 33.3 33.3 Adrenal gland (n=2) 100 100 Intra-abdominal implantation (n=2) 100 100
The response of MVTT to combined LEN and anti-PD-1 antibodies was higher versus HCC tumors in other sites. The mechanisms underlying this differential response warrant further investigation.
The authors.
Has not received any funding.
All authors have declared no conflicts of interest.