PD-1 inhibitors plus lenvatinib versus PD-1 inhibitors plus regorafenib in patients with advanced hepatocellular carcinoma after failure of sorafenib

Abstract

BackgroundLenvatinib, regorafenib and anti-programmed cell death protein-1 (PD-1) immunotherapy have shown promising clinical outcomes in patients with advanced hepatocellular carcinoma (HCC) after sorafenib failure, respectively. However, the combination of the two treatments has not been reported. We compared the efficacy of PD-1 inhibitors with lenvatinib (PL) and PD-1 inhibitors plus regorafenib (PR) in patients with advanced HCC in this study.MethodsWe conducted a retrospective study of advanced HCC patients who undergone PD-1 inhibitors combined with lenvatinib or regorafenib after failure of sorafenib at Second Affiliated Hospital of Nanchang University from July 2018 and December 2020. The overall survival (OS), progression-free survival (PFS), effective rates and treatment-related adverse events (TRAEs) were investigated.ResultsIn total, 61 patients met the criteria and were included in the present study, and they were divided into the PL group (n = 32) and PR group (n = 29). The overall response rate (ORR) (12.5%vs. 10.3%, respectively; p = 0.557) and disease control rate (DCR) (71.9%vs. 58.6%, respectively; p < 0.207) were higher in the PL group than in the PR group, but there was no statistical difference.Furthermore, median PFS and OS were not significantly different between the two groups in Kaplan-Meier survival analysis (PFS: 5.3 months vs 4.0 months, p = 0.512; OS: 14.1 months vs 13.7 months, p = 0.764 for the PL group vs PR group). The most common treatment-related adverse events (TRAEs) were hand -foot skin reaction (24/61,39.3%), hypertension (20/61,32.8%) and hypothyroidism (13/61,21.3%). The frequent TRAEs (≥Grade 3) during PD-1 inhibitors plus lenvatinib or regorafenib treatment were hand-foot skin reaction (5/29,12.4%), thrombocytopenia (2/29 6.90%) and proteinuria (n =2/32,6.25%).ConclusionsCombination of lenvatinib/regorafenib and PD-1 inhibitors is a promising therapy for HCC patients after sorafenib failure.

Efficacy and safety of transarterial chemoembolization combined with first-line tyrosine kinase inhibitors and programmed death-1 inhibitors for progressed hepatocellular carcinoma

“…In this work, the median OS of patients who received TACE plus rst-line TKI plus PD-1 inhibitors was 15.0 months, consistent with prior work that revealed an OS of 14.9 months. The median PFS of these patients was 11.0 months in the present study, which was greater than that observed in a previous study that reported a PFS of 4.2 months [22]. This difference in PFS might be explained by variations in baseline patient characteristics: the previous trial included a larger proportion (88.4%) of patients with liver cirrhosis (only 52.1% in our study).…”

“…However, for these patients, the survival obtained by PD-1 inhibitor monotherapy is still unsatisfactory [19]. Thereby, PD-1 inhibitors in combination with other treatments (such as TACE and TKI) are being considered for these uHCC patients during second-line therapy; for instance, a recent study suggested that, as the second-line therapy for uHCC patients, PD-1 inhibitors in combination with rst-line TKI (e.g., sorafenib) can prolong the survival time (i.e., the median OS can reach 14.1 months and the median PFS can reach 5.3 months) [22].…”

Biomimetic Responsive Nanoconverters with Immune Checkpoint Blockade Plus Antiangiogenesis for Advanced Hepatocellular Carcinoma Treatment

“…First, patient eligibility is restricted with only those meeting the current inclusion criteria (limited to cases with a Child–Pugh A score) being considered, primarily because of the occurrence of severe immune-related adverse events resulting from the long half-life and off-target effects of mAbs. , Second, the high cost of treatment is rooted in the complexity of mAb production. , Consequently, recent clinical studies have shown a growing inclination toward the incorporation of more cost-effective small-molecule inhibitors. Thus, the combination of small-molecule TKIs with antiangiogenesis properties, such as apatinib (Apa), regorafenib, or lenvatinib, with mAb targeting of PD-1/PD-L1, has displayed enhanced antitumor efficacy in clinical trials for treating advanced HCC. − Certainly, the contrasting physicochemical properties inherent to these two types of drugs produce distinct pharmacokinetic profiles. Consequently, when employed concurrently, this divergence in their pharmacokinetics may result in a notable delay in achieving the desired therapeutic effectiveness.…”

Lenvatinib Plus PD-1 Inhibitors versus Regorafenib in Patients with Advanced Hepatocellular Carcinoma After the Failure of Sorafenib: A Retrospective Study

“…Thyroid cancer, kidney cancer, liver cancer, and endometrial cancer have all been treated with lenvatinib on a large scale. 18 , 19 Although the overall survival (OS) of lenvatinib was not inferior to that of sorafenib (13.6 months vs 12.3 months) according to REFLECT, the progression-free survival (PFS) was significantly better (7.4 months vs 3.7 months, p<0.0001). 20 The NCCN guidelines also recommend that lenvatinib be selected as a second-line treatment for sorafenib-resistant HCC.…”

“…Abbreviations: H.R, hazard ratio; CI, confidence interval; ECOG PS, Eastern Cooperative Oncology Group Performance status; AFP, alpha fetoprotein; BCLC, Barcellola Clinic Liver Cancer; HBV, hepatitis B virus; TACE, transarterial chemoembolization; HAIC, hepatic artery infusion chemotherapy.https://doi.org/10.2147/TCRM.S420371DovePressTherapeutics and Clinical Risk Management 2023:19 …”