Search

Background: Immune checkpoint inhibitors (ICIs) have demonstrated superior clinical efficacy in prolonging overall survival (OS) as the second-line treatment for advanced or metastatic esophageal squamous cell carcinoma (ESCC), and were recommended by the guidelines. However, it remains uncertain which ICI is the most cost-effective. This study assessed the cost-effectiveness of ICIs as the second-line treatment for ESCC based on the perspective of the Chinese healthcare system. Methods: A network meta-analysis (NMA) was performed to obtain the Hazard ratios (HRs) for indirect comparisons. A three-state Markov model with a 10-year time horizon was conducted to assess the cost-effectiveness. The state transition probabilities were calculated with Kaplan-Meier (KM) curves data from clinical trial and HRs from the NMA. Utilities and costs were derived from local charges or previously published studies. Univariate and probabilistic sensitivity analyses (PSA) were performed to examine model robustness. The results were assessed based on the total costs, quality-adjusted life years (QALYs), and incremental cost-effectiveness ratios (ICERs). Results: Five clinical trials (ATTRACTION-3, ESCORT, KEYNOTE-181, ORIENT-2, RATIONALE-302) with a total of 1797 patients were included in the NMA. The NMA showed that both camrelizumab and tislelizumab received relatively high rankings for progression-free survival (PFS) and OS. Compared with sintilimab, treatment with tislelizumab and camrelizumab gained 0.018 and 0.034 additional QALYs, resulting in incremental ICERs of $75,472.65/QALY and $175,681.9/QALY, respectively. Nivolumab and pembrolizumab produced lower QALYs and greater costs, suggesting that both were dominated in comparison to sintilimab. HRs and health state utilities were the most influential parameters in most univariate sensitivity analyses of paired comparisons. PSA results suggested that sintilimab had an 84.4% chance of being the most cost-effective treatment regimen at the WTP threshold of $38,223.34/QALY. In the scenario analysis, sintilimab would no longer be cost-effective, if the price of camrelizumab was assumed to decrease by 64.6% or the price of tislelizumab was assumed to decrease by 16.9%. Conclusions and relevance: Among the five potential competing ICIs, sintilimab was likely to be the most cost-effective regimen as the second-line treatment for locally advanced or metastatic ESCC in China. Key points: Question: Which immune checkpoint inhibitor (ICI) is the most cost-effective for the second-line treatment of the patients with metastatic esophageal squamous cell carcinoma (ESCC)? Findings: At a willingness-to-pay threshold of $38,223.34/QALY, sintilimab was cost-effective in 84.4% of the simulations, the highest of the ICIs. Meaning: Sintilimab was the most cost-effective option compared to other ICIs as the second-line therapy for ESCC in China. [ABSTRACT FROM AUTHOR]

Background: The regimen of nivolumab plus ipilimumab (NI) has been recommended by the National Comprehensive Cancer Network Clinical Practice Guidelines in Oncology-Malignant Pleural Mesothelioma (Version 1.2022) and Chinese Guidelines for the Clinical Diagnosis and Treatment of Malignant Pleural Mesothelioma (2021 edition) as the first-line treatment for Malignant Pleural Mesothelioma (MPM). But whether immunotherapy has a financial advantage over conventional chemotherapy (pemetrexed plus cisplatin/carboplatin, C) is uncertain. Methods: Based on survival and safety data from the CheckMate 743 clinical trial (NCT02899299), a partitioned survival model was constructed using TreeAge Pro2022 software. The model cycle was set to 1 month and the study period was 10 years. The output indicators included total cost, quality-adjusted life year (QALY) and incremental cost-effectiveness ratio (ICER). One-way and probabilistic sensitivity analyses were used to assess the robustness of the results, considering only direct medical costs. Results and discussion: The ICER for group NI versus Group C was $375,656/QALY in all randomized patients, $327,943/QALY in patients with epithelioid histology, and $115,495/QALY in patients with non-epithelioid histology. The ICERs of all three different populations all exceeded the willingness-to-pay threshold (three times the per capita gross domestic product of China in 2021). The results of univariate sensitivity analysis showed that the price of pemetrexed and nivolumab had great influence on the analysis results. The results of the probabilistic sensitivity analysis show that the probability of the NI scheme being more economical in all three different populations was 0. What is new and conclusion: From the perspective of the Chinese healthcare system, in patients with unresectable MPM, NI has no economic advantage over C. [ABSTRACT FROM AUTHOR]

Background: The aim of the study was to evaluate the cost-effectiveness of nivolumab plus chemotherapy as first-line treatment for patients with advanced gastric, gastroesophageal junction (GEJ), or esophageal adenocarcinoma from the perspective of Chinese and US society. Methods: To conduct the analysis, a state-transitioned Markov model, which included three mutually exclusive health states (progression-free survival (PFS), progressive disease (PD), and death), was developed. Cycle length was set at 3 weeks and lifetime horizon was set at 10 years. Costs, quality-adjusted life years (QALYs), and incremental cost-effectiveness ratio (ICER) were calculated in the analysis. Willingness-to-pay (WTP) thresholds in the model were set at $37,653.00/QALY in China and $100,000.00/QALY in the US, respectively. Meanwhile, one-way sensitivity analyses and probabilistic sensitivity analyses were conducted to investigate the robustness of the model. Results: Over a lifetime horizon, the ICERs of nivolumab plus chemotherapy versus chemotherapy alone were $430,185.04/QALY and $944,089.78/QALY in China and the US, respectively. Cost of nivolumab and utility for the PFS state had the most significant impact on ICERs both in the US and China based on the results of the one-way sensitivity analyses. In the probabilistic sensitivity analyses, the proportions of nivolumab plus chemotherapy being cost-effective compared with chemotherapy alone were 0%. Conclusions: In conclusion, nivolumab plus chemotherapy is unlikely to be a cost-effective treatment option compared with chemotherapy alone in the first-line setting of advanced gastric, GEJ, or esophageal adenocarcinoma. [ABSTRACT FROM AUTHOR]

Background: Anti-PD-1 antibodies have been approved for treating several cancer. However, data regarding the safety and efficacy of these agents in HIV-infected patients with cancer is lacking, because these patients are frequently omitted from clinical trials. Objectives: The primary aim of our research is to assess the safety, activity, and long-term outcomes of PD-1 inhibitors in the treatment of HIV-infected patients with advanced cancer. Method: We retrospectively analyzed data from HIV-infected patients with advanced cancers who were treated with PD-1 inhibitors at Shanghai Public Health Clinical Center, Shanghai, China. Results: Fifteen HIV-infected patients (all are men; asian; median age, 44) with cancer who were treated with chemotherapy and/or combined the other oncology treatments [along with combined antiretroviral therapy (cART)] prior to Sintilimab (12 out of 15) or Nivolumab (1 out of 11) or Camrelizumab (2 out of 11) injection were identified. Eight patients responded to treatment (disease control rate 53.3%), with 1 got partial response (PR) and 7 were stable. Most treatment-emergent adverse events (TEAEs) were grade 1 or 2 including anemia, leukopenia, hyperglycemia, granulocytopenia, and thrombocytopenia. Eight patients (53.3%) experienced treatment-related AEs (TRAEs) with grades 3/4including myelosuppression, infection, and neurological disorders. CD4+ T cell count and plasma HIV RNA remained stable throughout the treatment. Conclusions: When used in HIV-infected patients with advanced malignancies, PD-1 inhibitors tend to have favorable efficacy, manageable side effects, and no deteriorated impacts on plasma HIV-RNA and CD4+ T cell count. [ABSTRACT FROM AUTHOR]

Background and Objective: The programmed death 1 and ligand (PD‐1/PD‐L1) inhibitors have significantly altered therapeutic perspectives on non‐small‐cell lung cancer (NSCLC). However, their efficacy and safety are unknown since direct clinical trials have not yet been performed on them. It is also necessary to determine the economics of PD‐1/PD‐L1 inhibitors due to their high cost. The aim was to evaluate the efficacy, safety, and cost‐effectiveness of PD‐1/PD‐L1 inhibitor monotherapy for advanced NSCLC patients in China with high PD‐L1 expression as first‐line treatment. Methods: From the PubMed, Cochrane, and Web of Science databases, we retrieved survival, progression, and safety data on PD‐1/PD‐L1 inhibitor monotherapy for advanced NSCLC patients. A network meta‐analysis (NMA) was performed to consider PD‐1/PD‐L1 inhibitors in efficacy and safety. A Markov model with a full‐lifetime horizon was adopted. Clinical and utility data were collected through the trial. The cost per quality‐adjusted life year (QALY) was as incremental cost‐effectiveness ratio (ICER). Sensitivity analyses were performed. Results: This study included five phase III clinical trials using four drugs: nivolumab, pembrolizumab, atezolizumab, and durvalumab. The NMA demonstrated that the four drugs had similar efficacy and safety, while pembrolizumab and atezolizumab were better for than for nivolumab (hazard ratio (HR) = 0.66, 95% confidence intervals (CIs): 0.46–0.95 and HR = 0.59, 95%CI: 0.37–0.94) in progression‐free survival (PFS), and the risk of a severe adverse event was higher for atezolizumab than for nivolumab and pembrolizumab. Compared with nivolumab, durvalumab, pembrolizumab, and atezolizumab had QALY of 0.19, 0.38, and 0.53, respectively, which induced ICERs of $ 197,028.8/QALY, $ 111,859.0/QALY, and $ 76,182.3/QALY, respectively. Conclusion: The efficacy and safety are similar among types of PD‐1/PD‐L1‐inhibitor monotherapy. The cost‐effectiveness of nivolumab appears optimal, but the other PD‐1/PD‐L1 inhibitors are not as cost‐effective for the first‐line treatment of advanced NSCLC in China. [ABSTRACT FROM AUTHOR]

Nivolumab 240 mg every 2 weeks is approved in China by the National Medical Product Agency for squamous cell carcinoma of the head and neck and gastric cancer, based on population pharmacokinetic (PPK) analyses and benefit‐risk assessment of safety/efficacy in solid tumors, including Chinese and global populations. The aim of this assessment was to investigate exposure and risk for adverse events (AEs) with flat dosing compared with weight‐based dosing. Nivolumab 240‐mg and 3‐mg/kg every‐2‐week exposures in Chinese patients were simulated using PPK modeling, and AEs in Chinese and pooled global populations were compared by dosing regimen, exposure, and weight. The 10‐mg/kg every‐2‐week regimen was included because it is known to be well tolerated. Predicted nivolumab exposure in Chinese patients receiving 240 mg every 2 weeks was ∼25% higher versus 3 mg/kg every 2 weeks, but ∼60% lower versus 10 mg/kg every 2 weeks. Grade 3/4 AE incidence in Chinese patients receiving nivolumab 3 mg/kg every 2 weeks was similar with 240‐mg every‐2‐week dosing and with patients from global populations treated with 3 or 10 mg/kg every 2 weeks. There was no trend toward increased AE incidence with high versus low nivolumab exposure or in global patients of varying body weight receiving 3 or 10 mg/kg every 2 weeks. Objective response rates were similar in Chinese and global patients with squamous and nonsquamous NSCLC. Results showed that benefit‐risk profiles with nivolumab 240 mg every 2 weeks were similar to those of the 3‐mg/kg every‐2‐week regimen in Chinese patients and global populations, providing an alternative treatment option to Chinese patients. [ABSTRACT FROM AUTHOR]

• Nivolumab improves overall survival in advanced HCC. • The study evaluated the cost-effectiveness of the new strategy. • The new strategy is not cost-effective from Chinese perspective. • The HR for OS and cost of nivolumab have great effects on the results. • It would become cost-effective when the cost of nivolumab was discounted by 70%. Nivolumab improves overall survival (OS) and is associated with less adverse events (AE) compared with sorafenib in the first-line treatment of advanced hepatocellular carcinoma (HCC). But which approach is the most cost-effective remains uncertain. This study aimed to evaluate the cost-effectiveness of nivolumab vs sorafenib as first-line therapy for patients with advanced HCC from the perspective of Chinese healthcare system. A partitioned survival mode was constructed to evaluate the health and economic outcomes of nivolumab vs sorafenib as first-line treatment for advanced HCC. The clinical data and outcomes were obtained from CheckMate 459 trial. Medical costs and utilities were collected from published sources. Quality-adjusted life-years (QALYs) and incremental cost-effectiveness ratio (ICER) were calculated. One-way and probabilistic sensitivity analyses were used to examine model uncertainty. Additional subgroup and scenario analyses were performed. Treatment with nivolumab yielded an additional 0.27 QALYs with an incremental cost of $65,579.19 compared with sorafenib, leading to an ICER of $236,765.93/QALY in China. One-way sensitivity analysis found the model outputs to be most affected for hazard ratio (HR) of OS and the cost of nivolumab. Probabilistic sensitivity analysis showed that the probability of nivolumab being cost-effective was 0% at the willingness-to-pay (WTP) threshold of $38,201.19/QALY. The scenario analyses indicated altering the time horizon of the model did not reverse the economic results. Nivolumab as first-line treatment could gain more health benefits for advanced HCC compared with sorafenib, but was estimated not to be cost-effective at the commonly adopted WTP threshold of China. [ABSTRACT FROM AUTHOR]

The outcome of small cell lung cancer (SCLC) patients is poor because rapid metastasis develops after first‐line chemotherapy and few drugs are available for second‐line chemotherapy. The median survival rate has not significantly changed in recent years. In this report, we discuss the case of a 71‐year‐old Chinese female non‐smoker diagnosed with extensive‐stage SCLC who was treated with nivolumab for a short period and obtained a prolonged clinical benefit. We report the clinical history, clinical features, potential mechanism, benefits, and the best therapeutic window. The patient was treated with transcatheter arterial chemoembolization because of liver metastasis and then with four doses of nivolumab as third‐line systemic treatment. There was no disease progression for 15 months. The lesions became larger than before, suggesting disease progression, thus nivolumab treatment was ceased. Immunotherapy has the capacity to turn combined therapy into a feature that may be exploited for clinical benefit. Further research is required to evaluate whether combined treatment is beneficial for patients, affecting the efficacy of immunotherapy, and to determine the best therapeutic window for clinical treatment. [ABSTRACT FROM AUTHOR]

Background: Nivolumab is a new standard of care for patients with metastatic renal cell carcinoma (mRCC) and provides an overall survival benefit of 5.40 months in comparison with everolimus. This study evaluated the cost-effectiveness of nivolumab for the second-line treatment of mRCC from the perspective of US payers and identified the range of drug costs for which the addition of nivolumab to standard therapy could be considered cost-effective from a Chinese perspective.Methods: A partitioned survival model was constructed to estimate lifetime costs, life-years, and quality-adjusted life-years (QALYs). Costs were estimated for the US and Chinese health care systems. One-way and probabilistic sensitivity analyses were performed.Results: Nivolumab provided an additional 0.29 QALYs at a cost of $151,676/QALY in the United States. The probabilistic sensitivity analysis showed that at a willingness-to-pay threshold of $100,000/QALY, at the current cost of nivolumab, the chance of nivolumab being cost-effective was 3.10%. For China, when nivolumab cost less than $7.90 or $9.70/mg, there was a nearly 90% likelihood that the incremental cost-effectiveness ratio for nivolumab would be less than $22,785 or $48,838/QALY, respectively.Conclusions: For the United States, nivolumab is unlikely to be a high-value treatment for mRCC at the current price, and a price reduction appears to be justified. In China, value-based prices for nivolumab are $7.90 and $9.70/mg for the country and Beijing City, respectively. This study could and should inform the multilateral drug-price negotiations in China that may be upcoming for nivolumab. Cancer 2017;123:2634-41. © 2017 American Cancer Society. [ABSTRACT FROM AUTHOR]

• Nivolumab plus ipilimumab showed great efficacy in NSCLC. • The study evaluated the cost-effectiveness of the new strategy. • The new strategy is not cost-effective from Chinese perspective. • The HR for OS and patient weight have great effects on the results. • It would become cost-effective when the costs of two ICIs were discounted by 70%. First-line treatment with nivolumab plus ipilimumab has been shown to improve overall survival (OS) and progression-free survival (PFS) for patients with advanced non-small cell lung cancer (NSCLC). The current study evaluated the cost-effectiveness of nivolumab plus ipilimumab versus chemotherapy in advanced NSCLC from the perspective of Chinese healthcare system. A three state-transition Markov model was employed to evaluate the cost and effectiveness of nivolumab plus ipilimumab versus chemotherapy in the first-line treatment of advanced NSCLC. Key clinical data in the model were derived from Part 1 of the phase 3 CheckMate 227 trial (NCT02477826). Costs and utilities were obtained from published literatures. The main endpoints of the model were costs, quality-adjusted life-years (QALYs) and incremental cost-effectiveness ratio (ICER). One-way and probabilistic sensitivity analyses were performed to assess the model uncertainty. Nivolumab plus ipilimumab was associated with an increase in overall cost of $95,867.82 and improved effectiveness of 0.98 QALYs compared with chemotherapy, yielding an ICER of $97,676.24 per QALY. In one-way sensitivity analysis, the variables that had the greatest influence on the ICER were hazard ratio for OS and body weight. In probabilistic analysis, nivolumab plus ipilimumab had a 0% probability of being cost-effective at a willingness-to-pay (WTP) threshold of $37,663.26/QALY in China. However, the combination therapy would become cost-effective when the cost of nivolumab and ipilimumab were discounted by 65%. First-line nivolumab plus ipilimumab treatment for advanced NSCLC was found to be not cost-effective compared with chemotherapy at a WTP threshold of $37,663.26/QALY in China. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma (HCC) has an increasing incidence worldwide, and the global 5-year survival rate ranges from 5–30%. In China, HCC seriously threatens the nation's health; the incidence of HCC ranks fourth among all theriomas, and the mortality rate is the third highest worldwide. The main therapies for HCC are surgical treatment or liver transplantation; however, most patients with HCC will experience postoperative recurrence or metastasis, eventually resulting in mortality. As for advanced or unresectable HCC, the current appropriate treatment strategy is transarterial chemoembolization; however, limited therapeutic effect and natural or acquired drug resistance affect the efficacy of this approach. Previous studies have demonstrated that PD-L1 expression on host cells and myeloid cells plays an important role in PD-L1 blocked-mediated tumor regression. Thus, further research on programmed cell death protein 1 (PD-1) and programmed death-ligand 1 (PD-L1) is required. Countries including the United States, France, Britain and China have developed PD-1/PD-L1 blockers, including nivolumab, pembrolizumab, cemiplimab, atezolizumab, avelumab, durvalumab, toripalimab, sintilimab and camrelizumab. Notably, all of these blockers have therapeutic effect and influencing factors in HCC. Factors that influence the clinical outcome of PD-1 have also been discovered, such as inflammatory genes, specific receptors and signaling pathways. The discovery of these factors will help to identify novel methods, such as combination treatment, to decrease the influence of other factors on the efficacy of PD-1/PD-L1. Sorafenib and lenvatinib have been approved for first-line treatment for patients with advanced HCC. When first-line treatment frequently fails, pembrolizumab and ipilimumab plus nivolumab are used following sorafenib (but not lenvatinib) treatment in advanced HCC. Thus, tumor immunotherapy using PD-1/PD-L1 blockers exhibits promising outcomes for the treatment of HCC, and more novel PD-1/PD-L1 inhibitors are being developed to fight against this disease. The present review discusses the clinical results and influencing factors of PD-1/PD-L1 inhibitors in HCC to provide insight into the development and optimization of PD-1/PD-L1 inhibitors in the treatment of HCC. [ABSTRACT FROM AUTHOR]

Background HLX10, a fully humanized IgG4 monoclonal antibody against the programmed death-1 (PD-1) receptor blocking PD-1, increased functional activities of human T-cells and showed in-vitro antitumour activity in xenograft models. The combined inhibition of PD-1 and VEGFR pathways may enhance a sustained suppression of cancer-related angiogenesis and tumour growth. Here, we present the phase 1 study data of HLX10 and the development of HLX10 as targeted combination immunotherapy. Methods We conducted an open-label, dose-finding with Bayesian optimal interval adaptive design study to evaluate safety, maximum tolerated dose, PK and clinical activity of HLX10 in patients with advanced or metastatic solid tumours refractory to standard therapy. Patients (pts) received biweekly i.v. infusions of HLX10 at doses of 0.3, 1, 3 and 10 mg/kg until disease progression, intolerable toxicities or withdrawal from the study. The dose-limiting toxicities were observed for 28 days after treatment. Clinical response was evaluated every 8 weeks for the first 24 weeks followed by every 12 weeks. Safety, PK and clinical response evaluations were performed throughout the study. Results As of 27-June-2019, 16 pts were dosed with HLX10 at various doses and maintained >90% PD1 receptor occupancy on the peripheral T-cells. Among 13 pts being evaluated for efficacy, 2 pts each at 0.3 and 3 mg/kg cohorts achieved stable disease; 1 pt at 3 mg/kg cohort achieved partial response with the longest follow-up time of 220 days. No infusionrelated reaction or additional safety signal was observed up to 10 mg/kg. The PK profiles demonstrated dose proportional manner as shown in the table. Table: 324P The PK parameters of 0.3 mg/kg and 3 mg/kg cohorts Dose(mg/kg)  Cmax (μg/mL)   AUC0-t (h* μg/mL)   t1/2 (h)   -  C1D1  C3D1  C1D1  C3D1  C1D1  C3D3  0.3  5.3  6.3  702.1  957.1  183.4  183.0  3  74.8  117.2  10823.6  27750.9  259.7  489.81  Dose(mg/kg)  Cmax (μg/mL)   AUC0-t (h* μg/mL)   t1/2 (h)   -  C1D1  C3D1  C1D1  C3D1  C1D1  C3D3  0.3  5.3  6.3  702.1  957.1  183.4  183.0  3  74.8  117.2  10823.6  27750.9  259.7  489.81  Table: 324P The PK parameters of 0.3 mg/kg and 3 mg/kg cohorts Dose(mg/kg)  Cmax (μg/mL)   AUC0-t (h* μg/mL)   t1/2 (h)   -  C1D1  C3D1  C1D1  C3D1  C1D1  C3D3  0.3  5.3  6.3  702.1  957.1  183.4  183.0  3  74.8  117.2  10823.6  27750.9  259.7  489.81  Dose(mg/kg)  Cmax (μg/mL)   AUC0-t (h* μg/mL)   t1/2 (h)   -  C1D1  C3D1  C1D1  C3D1  C1D1  C3D3  0.3  5.3  6.3  702.1  957.1  183.4  183.0  3  74.8  117.2  10823.6  27750.9  259.7  489.81  Conclusions HLX10 is well tolerated, shows promising antitumour activities with durable objective responses in various cancers, and exhibits similar PK results to pembrolizumab and nivolumab. HLX10 is currently being tested in the first China combo-immunotherapy studies with HLX04 (a bevacizumab biosimilar) in advanced solid tumours with the longest follow-up time of > 200 days as of 20-June-2019 and in first-line treatment of metastatic NSCLC. Clinical trial identification HLX10-001(Registration Number: NCT0346875) monotherapy in advanced solid tumours; HLX10HLX04-001(Registration Number: NCT03757936) combo-immunotherapy in advanced solid tumours; HLX10-002-NSCLC301(Registration Number: NCT03952403) combo-immunotherapy in NSCLC. Legal entity responsible for the study Shanghai Henlius Biotech, Inc; Taiwan Henlix Biotech. Co.LTD. Funding Shanghai Henlius Biotech, Inc. Disclosure T.Y. Chao: Research grant / Funding (institution): Taiwan Henlix Biotech. Co. LTD. C.L. Ho: Research grant / Funding (institution): Taiwan Henlix Biotech. Co. LTD. W.H. Cheng: Research grant / Funding (institution): Taiwan Henlix Biotech. Co. LTD. C.L. Chang: Research grant / Funding (institution): Taiwan Henlix Biotech. Co. LTD. Y.Y. Hsieh: Research grant / Funding (institution): Taiwan Henlix Biotech. Co. LTD. W. Jiang: Full / Part-time employment: Shanghai Henlius Biotech, Inc. S. Liu: Full / Part-time employment: Shanghai Henlius Biotech,Inc. A. LUK: Full / Part-time employment: Shanghai Henlius Biotech, Inc. S.F. Lin: Full / Part-time employment: Taiwan Henlix Biotech. Co. LTD. T.C. Hsieh: Full / Part-time employment: Taiwan Henlix Biotech. Co. LTD. E. Liu: Full / Part-time employment: Taiwan Henlix Biotech. Co. LTD. [ABSTRACT FROM AUTHOR]