Immunotherapy or targeted therapy as the first-line strategies for unresectable hepatocellular carcinoma: A network meta-analysis and cost-effectiveness analysis

Abstract

IntroductionThe existence of many phase III randomized controlled trials (RCTs) of first-line treatment for unresectable hepatocellular carcinoma (HCC) puzzle doctors and patients in choosing the most effective treatment strategies. We aimed to assess the efficacy, safety, and cost-effectiveness of immunotherapy or targeted therapy as the first-line strategy for unresectable HCC.MethodsThe included clinical trials were retrieved from PubMed, Embase, the Cochrane library, and Web of Science databases, in which immunotherapy or targeted therapy was regarded as the first-line treatment for unresectable HCC, published in English between January 1, 2010, and September 20, 2022. We conducted a network meta-analysis (NMA) and cost-effectiveness analysis (CEA) from the Chinese payer’s perspective. Overall survival (OS), progression-free survival (PFS), the ranks of different treatments using P-score, and adverse events (AEs) were evaluated by NMA. Total costs, life-years (LYs), quality-adjusted life-years (QALYs), and incremental cost-benefit ratio (ICER) were estimated from 15-year Markov models developed by CEA.ResultsWe identified 2,825 records, including 11,796 patients, from 15 RCTs. The NMA revealed that sintilimab plus a bevacizumab biosimilar (HR, 0.57; 95% CI, 0.43 to 0.75; P = 0.96) and camrelizumab plus rivoceranib (HR, 0.56; 95% CI, 0.41 to 0.66; P = 0.94) could lead to great improvements in OS and PFS compared with sorafenib-related survival. The CEA indicated that tislelizumab increased by 0.220 QALYs (0.312 LYs) and decreased by $1,938 compared with sorafenib, which yielded ICERs of -$8,809/QALY (-$2,612/LY). Sensitivity analysis showed that the model was stable.ConclusionSintilimab plus a bevacizumab biosimilar and camrelizumab plus rivoceranib significantly prolonged OS and PFS, respectively. Further considering the pharmacoeconomics factors, tislelizumab is the most cost-effective first-line treatment strategy for unresectable HCC in China.

Immune checkpoint inhibitor for patients with advanced biliary tract cancer: A cost‐effectiveness analysis

“…12,13,15 And visual examination together with the Akaike and Bayesian information criteria (AIC and BIC) were used to determine which of the Exponential, Log-logistic, Log-normal, Gompertz and Weibull distributions best fit the parameters of the established model (Supporting Information Figure S2 and Table S4). 17,18 After selecting the Weibull distribution, calculations were performed for the scale (λ) and shape (γ) parameters (Table 1). 17,18 A frequency network meta-analysis was then selected to perform indirect comparisons, with HR values associated with the durvalumab plus GemCis versus pembrolizumab plus GemCis regimens (.92 [.73-1.15] and .86 [.69-1.07]) (Table 1) being derived using a fixed-effects meta-regression model (Table 1).…”

“…17,18 After selecting the Weibull distribution, calculations were performed for the scale (λ) and shape (γ) parameters (Table 1). 17,18 A frequency network meta-analysis was then selected to perform indirect comparisons, with HR values associated with the durvalumab plus GemCis versus pembrolizumab plus GemCis regimens (.92 [.73-1.15] and .86 [.69-1.07]) (Table 1) being derived using a fixed-effects meta-regression model (Table 1). [18][19][20] Model construction, data extraction and parameter calculations were respectively performed with TreeAge Pro 2022, GetData Graph Digitizer (v 2.26) and the 'netmeta' package in Rstudio (v 1.2.5042).…”

“…Key outcome endpoints for this analysis included total cost, quality-adjusted life years (QALYs), life years (LYs), incremental costeffectiveness ratio (ICER) and incremental net-health benefit (INHB) at willingness-to-pay (WTP) thresholds of $100 000/QALY (USA) and $37 408/QALY (3 times China GDP in 2022). 18,21 Total costs and health values were discounted at respective rates of 3% and 5% annually in the USA and China. 22…”

“…22 Grade 3 or higher treatment-associated adverse events (AEs) were assigned a mean disutility value of .073 as a means of assessing deteriorating patient QoL (Table 1). [17][18][19][22][23][24][25] The present study considered direct costs, including the costs of drugs, administration, laboratory testing, imaging, grade 3 or higher AE management (for AEs with ≥5% incidence), BSC and terminal care (Table 1). Real-world hospital data and information from the Centers for Medicare & Medicaid Services were used to determine drug costs.…”

“…26 While other direct medical costs were derived from prior publications. [17][18][19]22,25,27 Costs were adjusted for inflation to 2023 prices based on the USA consumer price index (CPI). 28 No inflation adjustments were performed for drug pricing in China, as the Chinese government regulates healthcare costs and ensures that they remain stable.…”