Cost-effectiveness analysis of tislelizumab vs. camrelizumab for the treatment of second-line locally advanced or metastatic esophageal squamous cell carcinoma.

BACKGROUND: Esophageal carcinoma is a type of cancer that occurs in the esophagus. For patients with locally advanced or metastatic esophageal squamous cell carcinoma who have either experienced disease progression following first-line standard chemotherapy or are intolerant to it, the prognosis is typically poor. Additionally, these patients often bear a substantial economic burden during the course of their treatment. Tislelizumab is a selective PD-1 inhibitor with efficacy proven in locally advanced or metastatic esophageal squamous cell carcinoma. The study aims to evaluate the cost-effectiveness of tislelizumab versus camrelizumab as the second-line treatment in locally advanced or metastatic esophageal squamous cell carcinoma (ESCC) patients in China. METHODS: From the perspective of China's healthcare system, the partitioned survival model with three health states was established in a 3-week cycle and a lifetime horizon. Anchored matching adjusted indirect comparison was used for survival analyses based on individual patient data from RATIONALE 302 trial and the published ESCORT study due to the lack of head-to-head clinical trials. Only direct medical costs were included. Costs and utility values were derived from local charges, the published literature, and related databases. Sensitivity analyses and a scenario analysis were also performed to verify the robustness of the model results. RESULTS: Compared with camrelizumab monotherapy, tislelizumab monotherapy incurred a lower lifetime cost ($8,346 vs. $8,851) and yielded higher quality-adjusted life-years (QALYs) (0.87 vs. 0.63), which resulted in an incremental cost-effectiveness ratio (ICER) of -$2,051/QALY. Tislelizumab monotherapy is a dominant option over camrelizumab monotherapy in China. The three primary parameters upon which this result was most sensitive were the unit cost of camrelizumab, the unit cost of tislelizumab, and the duration of reactive cutaneous capillary endothelial proliferation (RCCEP). According to the probabilistic sensitivity analysis (PSA), tislelizumab monotherapy was 100% cost-effective when the WTP was 1-3 times GDP per capita in China($11,207/QALY∼$33,621/QALY). Scenario analysis showed that the result was consistent. CONCLUSION: Tislelizumab monotherapy is a dominant option compared with camrelizumab monotherapy as the second-line treatment for locally advanced or metastatic ESCC in China.

Immunotherapy Guided by Immunohistochemistry PD-L1 Testing for Patients with NSCLC: A Microsimulation Model-Based Effectiveness and Cost-Effectiveness Analysis.

BACKGROUND: On the basis of immunohistochemistry PD-L1 testing results, patients with advanced non-small cell lung cancer (NSCLC) are treated differently. Theoretically, patients with high PD-L1 expression (50% or 1%) should receive PD-1 monotherapy for fewer adverse reactions and cost savings from avoiding chemotherapy; however, there is controversy surrounding the cut-off criteria (1% or 50%) for immunohistochemistry testing and threshold for PD-1 monotherapy. OBJECTIVE: This study aims to predict the effectiveness and cost-effectiveness of different immunotherapy strategies for patients with NSCLC in China from the healthcare system perspective. PATIENTS AND METHODS: A microsimulation model was developed to evaluate the effectiveness and cost-effectiveness of three treatment strategies: PD-L1 testing (1%) (PD-1 monotherapy for those with PD-L1 expression at 1% threshold, and combination with chemotherapy for others with immunohistochemistry testing), PD-L1 testing (50%) (PD-1 monotherapy for those with PD-L1 expression at 50% threshold, and combination with chemotherapy for others with immunohistochemistry testing), and No PD-L1 testing (PD-1 combined with chemotherapy without immunohistochemistry testing). The model assumed 1000 patients per strategy, with each patient entering a unique clinical path prior to receiving treatment on the basis of PD-L1 test results. Clinical inputs were derived from clinical trials. Cost and utility parameters were obtained from the database and literature. One-way probabilistic sensitivity analyses (PSA) and six scenario analyses were used to test the model's robustness. RESULTS: The study revealed a hierarchy of survival benefits across three strategies, with No PD-L1 testing demonstrating the most survival advantage, followed by PD-L1 testing (50%), and finally, PD-L1 testing (1%). The comparative analysis demonstrated that No PD-L1 testing significantly enhanced overall survival (OS) (HR 0.85, 95% CI 0.78-0.93), progression-free survival (HR 0.82, 95% CI 0.75-0.90), and progression-free2 survival (PFS2) (HR 0.91, 95% CI 0.83-0.99) when juxtaposed against PD-L1 testing (1%). However, these improvements were not as pronounced when compared with PD-L1 testing (50%), particularly in relation to PFS, PFS2, and OS. The cost-effectiveness analysis further unveiled incremental cost-utility ratios (ICUR), with No PD-L1 testing versus PD-L1 testing (50%) at $34,003 per quality-adjusted life year (QALY) and No PD-L1 testing versus PD-L1 testing (1%) at $34,804 per QALY. In parallel, the ICUR for PD-L1 testing (50%) versus PD-L1 testing (1%) stood at $35,713 per QALY. Remarkably, the PSA result under a willingness-to-pay (WTP) threshold of $10,144 per QALY, with a 100% probability, demonstrated PD-L1 testing (1%) as the most cost-effective option. CONCLUSIONS: The survival benefits of PD-1 monotherapy for high expression with PD-L1 immunohistochemistry testing are inferior to those of PD-1 combined with chemotherapy without testing, but it is found to be more cost-effective at the WTP thresholds in China and holds great potential in increasing affordability and reducing the economic burden.

Cost-effectiveness of anlotinib vs. pembrolizumab and nivolumab as third-line treatment in recurrent small cell lung cancer in China.

BACKGROUND: The study aims to evaluate the cost-effectiveness of anlotinib versus pembrolizumab and nivolumab as the third-line treatment in recurrent small cell lung cancer (SCLC) patients from the Chinese healthcare system perspective. RESEARCH DESIGN AND METHODS: A Markov model was built to simulate the costs and health outcomes in the 4-year horizon. Efficacy and safety data of anlotinib, pembrolizumab, and nivolumab in patients with recurrent SCLC were derived from three studies. Cost and utility values were derived from local charges, the published literature, and related databases. Three scenario analyses and sensitivity analyses were performed to explore the robustness of the results. RESULTS: Compared with anlotinib, pembrolizumab and nivolumab were estimated to gain an additional 0.18 and 0.10 quality-adjusted life years (QALYs) at an incremental cost of $10,446 and $5,182, resulting in an increment cost-utility ratio (ICUR) of $58,221/QALY and $56,733/QALY. The sensitivity analyses showed that the likelihood of anlotinib being cost-effective was 87.5% to 99.9% at a willingness-to-pay (WTP) threshold of $11,144 to $33,431/QALY. The scenario analyses indicated that the results varied in different scenarios. CONCLUSIONS: The findings suggest that anlotinib could be the most cost-effective option versus pembrolizumab and nivolumab in the third-line treatment of recurrent SCLC from the Chinese healthcare system perspective.

The efficacy and safety of eravacycline compared with current clinically common antibiotics in the treatment of adults with complicated intra-abdominal infections: A Bayesian network meta-analysis.

Background: Eravacycline is a novel, fully synthetic fluorocycline antibiotic for the treatment of adults with complicated intra-abdominal infections (cIAIs). However, the efficacy and safety of eravacycline compared with current clinically common antibiotics remain unknown. Objective: This study aims to compare the efficacy and safety of eravacycline and other clinically common antibiotics in China, including tigecycline, meropenem, ertapenem, ceftazidime/avibactam+metronidazole, piperacillin/tazobactam, imipenem/cilastatin, and ceftriaxone+metronidazole, for the treatment of adults with cIAIs and to provide a reference for clinical choice. Methods: The PubMed, Embase, Cochrane Library, and ClinicalTrials.gov databases were electronically searched to collect clinical randomized controlled studies (RCTs) comparing different antibiotics in the treatment of patients with cIAIs from inception to June 1, 2021. Two reviewers independently screened the literature, extracted data, and evaluated the risk of bias in the included studies. Results: A total of 4050 articles were initially retrieved, and 25 RCTs were included after screening, involving eight treatment therapies and 9372 patients. The results of network meta-analysis showed that in the intention-to-treat (ITT) population, the clinically evaluable (CE) population, and the microbiologically evaluable (ME) population, the clinical response rate of eravacycline was not significantly different from that of the other 7 therapies (P > 0.05). In terms of microbiological response rate, eravacycline was significantly better than tigecycline [tigecycline vs. eravacycline: RR = 0.82, 95%CI (0.65,0.99)], and there was no significant difference between the other 6 regimens and eravacycline (P > 0.05). In terms of safety, the incidence of serious adverse events, discontinuation rate, and all-cause mortality of eravacycline were not significantly different from those of the other 7 treatment therapies (P > 0.05). Conclusion: Based on the evidence generated by the current noninferiority clinical trial design, the efficacy and safety of eravacycline for the treatment of adults with cIAIs are not significantly different from those of the other 7 commonly used clinical antibiotics in China. In terms of microbiological response rate, eravacycline was significantly better than tigecycline. In view of the severe multidrug-resistant situation in China, existing drugs have difficulty meeting the needs of clinical treatment, and the new antibacterial drug eravacycline may be one of the preferred options for the treatment of cIAIs in adults.

Cost-effectiveness analysis of sintilimab + chemotherapy versus camrelizumab + chemotherapy for the treatment of first-line locally advanced or metastatic nonsquamous NSCLC in China.

BACKGROUND AND OBJECTIVE: Sintilimab is a selective PD-1 inhibitor with efficacy in advanced or metastatic nonsquamous non-small-cell lung cancer (NSCLC) patients. This study evaluated the cost-effectiveness of sintilimab + chemotherapy versus camrelizumab + chemotherapy as the first-line treatment for locally advanced or metastatic nonsquamous NSCLC in Chinese patients. In addition, this study aimed to reveal the impact of the reference treatment choice on the incremental cost-effectiveness ratio (ICER) results. METHODS: A partitioned survival model (PSM) with three health states was constructed in a 3-week cycle with a lifetime horizon from the Chinese healthcare system perspective. Anchored matching adjusted indirect comparison was used for survival analyses based on individual patient data from Orient-11. Sintilimab + chemotherapy was chosen as the reference treatments in scenarios 1 and 2, while the camrelizumab + chemotherapy was chosen as the reference treatments in scenario 3. The utility values of different health states were derived from the patient-level European Organization for Research and Treatment Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) scores by mapping to the EQ-5D-5L, and QALYs were calculated as the health outcomes. One-way deterministic sensitivity analysis (DSA) and probability sensitivity analysis (PSA) were performed to explore model uncertainty. RESULTS: Compared to camrelizumab + chemotherapy, sintilimab + chemotherapy was associated with higher effectiveness (incremental QALYs ranged from 0.13-0.62) and lower total costs (incremental costs ranged from $1,099-$5,201), resulting in an ICER ranging from $6,440-$8,454/QALY. CONCLUSIONS: Sintilimab + chemotherapy is a cost-effective option compared with camrelizumab + chemotherapy as the first-line treatment for locally advanced or metastatic nonsquamous NSCLC in China.

The Relationship Between Short-Term Surrogate Endpoint Indicators and mPFS and mOS in Clinical Trials of Malignant Tumors: A Case Study of Approved Molecular Targeted Drugs for Non-Small-Cell Lung Cancer in China.

Objective: Due to the initiation of the priority review program in China, many antitumor drugs have been approved for marketing based on phase II clinical trials and short-term surrogate endpoint indicators. This study used approved targeted drugs for the treatment of non-small-cell lung cancer (NSCLC) in China as an example to evaluate the association between short-term surrogate endpoints [objective response rate (ORR) and disease control rate (DCR)] and median progression-free survival (mPFS) and median overall survival (mOS). Methods: Five databases, i.e., MEDLINE, Embase, Cochrane Library, China National Knowledge Infrastructure (CNKI), and Wanfang Data were searched, for phase II or phase III clinical trials of all molecular targeted drugs that have been marketed in China for the treatment of NSCLC. After screening the literature and extracting information, both univariate and multivariate linear regression were performed on the short-term surrogate indicators and mPFS and mOS to explore the relationship. Results: A total of 63 studies were included (25 studies with only ORR, DCR, and mPFS and 39 studies with ORR, DCR, mPFS, and mOS). In terms of the targeted drugs for the treatment of NSCLC, in addition to the good but not excellent linear relationship between DCR and mOS (0.4 < R2 adj = 0.5653 < 0.6), all other short-term surrogate endpoint indicators had excellent linear relationships with mPFS and mOS (R2 adj≥0.6), while mPFS and mOS had the most excellent linear relationships (R2 adj = 0.8036). Conclusion: For targeted drugs for the treatment of NSCLC, short-term surrogate endpoint indicators such as ORR and DCR may be reliable surrogate indicators for mPFS and mOS. However, whether short-term surrogate endpoint indicators can be used to predict final endpoints remains to be verified.

Will the Inducing and Maintaining Remission of Non-biological Agents and Biological Agents Differ for Crohn's Disease? The Evidence From the Network Meta-Analysis.

Background: Several drugs currently are available for the treatment of Crohn's disease, including non-biological agents such as anti-inflammatory agents, steroids, immunosuppressive agents, and biologic agents such as anti-tumor necrosis factor (TNF), anti-α4ß7 integrin, anti-alpha-4 integrin and anti-interleukin 12/23. However, the choice of treatments for induction and maintenance is still a challenge. The relevant comparison between non-biologic agents and biologic agents is few. In our research, we aimed to help making decisions, as well as providing clinicians and patients with medication references. Methods: We searched MEDLINE, Embase, and the Cochrane Central Register of controlled trials for relevant randomized controlled trials published through to July 2020 and systematic reviews published from January 2011 to December 2020. Search results were screened by 2 independent reviewers first by title and abstract and then by full text. Disagreements were resolved through discussion with a third reviewer. Results: 54 randomized controlled trials were included in our analysis. For induction of remission, azathioprine (OR, 3.5; 95% Crl, 1.4-8.9), infliximab (OR, 4.1; 95% Crl, 1.2-16.0), infliximab + azathioprine (OR, 7.0; 95% Crl, 1.2-41.0) and infliximab+ methotrexate (OR, 7.8; 95% Crl, 1.2-65.0) were more effective in first-line therapy than placebo. Adalimumab showed superiority to placebo in second-line therapy, but the range of SD was wide. For maintenance of remission, adalimumab (OR,2.24;95% Crl,1.17-4.76) and azathioprine (OR,2.05; 95% Crl,1.14-3.96) were more effective than placebo. Adalimumab (OR,0.56; 95%Crl,0.27-1.2), budesonide (OR,0.63; 95%Crl,0.26-1.6) and natalizumab (OR,0.65; 95%Crl,0.30-1.4) was associated with less risk of withdrawals when compared with placebo. Conclusion: For induction of remission, azathioprine, infliximab, and infliximab + azathioprine were more effective in first-line therapy. In second-line therapy, adalimumab was more effective but should be interpreted carefully. For maintenance of remission, adalimumab and azathioprine were more effective. Besides, adalimumab, budesonide, natalizumab had lower withdrawals. Therefore, biological agents were not always better than non-biological agents and they have their own advantages in different treatment methods of Crohn's disease.

Economic Evaluation of Rituximab + Recombinant Human Thrombopoietin vs. Rituximab for the Treatment of Second-Line Idiopathic Thrombocytopenic Purpura in China.

Objective: This study aimed to compare the economic evaluation of recombinant human thrombopoietin+rituximab (rhTPO + RTX) vs. RTX as second-line treatment for adult patients with immunologic thrombocytopenic purpura in China. Methods: The Markov model was used in our research. The response rate and relapse rate data were derived from two clinical trials and one retrospective study. Cost and utility values were derived from published literature, a third-party database, and healthcare documents. In addition, one-way sensitivity analysis and probabilistic sensitivity analysis were performed to observe the stability of the model and data source. Results: In the Markov model, compared with RTX, rhTPO+RTX yielded an additional 0.04 QALYs, with an incremental cost of 2,802 USD. The ICER was 69,097 USD/QALY. According to the results from the one-way sensitivity analysis, complete response of rhTPO+RTX, utility of complete response and response of RTX were the main drivers in the model. The results from the probabilistic sensitivity analysis demonstrated that there was a 100% probability that rhTPO+RTX was not cost-effective vs. RTX alone at a threshold of $10,805/QALY and an 84% probability at a threshold of $32,415/QALY. Conclusion: RTX+rhTPO was not more cost-effective than RTX alone as second-line treatment for adult patients with immunologic thrombocytopenic purpura in China.

Will the Markov model and partitioned survival model lead to different results? A review of recent economic evidence of cancer treatments.

Introduction: Balancing the high cost of treatment brought about by new therapies has become a problem that needs to be considered. Cost-effectiveness analysis (CEA) is a commonly used method that provides information on the potential value of new cancer treatments. The Markov and partitioned survival (PS) models are commonly used. Whether the results differ between the models in empirical research and the methodological differences remain unclear.Areas covered: A review was conducted to identify Canadian Agency for Drugs and Technologies in Health (CADTH) reports and papers published during the past 5 years that reported full economic evaluations of cancer treatments and used both models. In the included studies, most results except one obtained using the two models did not significantly differ.Expert opinion: Not enough evidence could support that there existed relevant bias in empirical studies about the PS model, and more methodological research and application of empirical research should be performed. We recommended that when individual data are available and the model structure is not complicated, the PS model is more appropriate. Both the PS and Markov models are recommended to assess model structure uncertainty.