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Programmed death receptor‐1 monoclonal antibodies (PD‐1 mAbs) have been applied in the treatment of different kinds of malignant tumors. However, a streamlined and expedited evaluation method for certain tumor types without approved indications is currently lacking in terms of their expandable applications. In this study, a novel evaluation method for the expandability of PD‐1 mAb was established for the first time. Clinical trial data of PD‐1 mAb in first‐line treatment for advanced gastric cancer were collected for comparison. For the first time, the clinical trial outcomes were analyzed through the entropy weight method and the technique for order preference by similarity to ideal solution (TOPSIS) method to evaluate the effectiveness and safety. The accessibility was assessed using the World Health Organization/Health Action International (WHO/HAI) standard survey method. Combining the results of effectiveness, safety, and accessibility, the recommendation for expandability of PD‐1 mAb was provided. Tislelizumab ranks seventh in effectiveness, higher than the chemotherapy group and the pembrolizumab group, and ranks fourth in safety evaluation and first in the combination chemotherapy groups. The annual drug cost of tislelizumab is 0.497 times the annual household income for urban residents of Shaanxi Province. 56.67% of medical institutions are equipped with tislelizumab in Shaanxi Province. These results indicate the promising efficacy and safety profile of tislelizumab in combination with chemotherapy as a first‐line treatment option for advanced gastric cancer. Notably, tislelizumab emerges as a more accessible alternative to sintilimab and boasts greater affordability compared to nivolumab and pembrolizumab. Consequently, tislelizumab should be considered a viable option for expandable application in first‐line treatment of advanced gastric cancer, contingent upon clinical necessity. [ABSTRACT FROM AUTHOR]

Background: Several economic studies have assessed the cost-effectiveness of programmed cell death protein-1 (PD-1) inhibitors compared to second-line chemotherapy in treating esophageal squamous cell carcinoma (ESCC). However, there is a lack of economic comparisons among the different PD-1 inhibitors. Aim: This study aimed to assess the cost-effectiveness of PD-1 inhibitors (nivolumab, pembrolizumab, camrelizumab, and tislelizumab) in second-line treatment for advanced or metastatic ESCC within the Chinese healthcare system. Method: The clinical trials were systematically retrieved from PubMed, Embase, Web of Science, and the Cochrane Library. We established a fractional polynomials model to conduct a network meta-analysis, enabling the calculation of hazard ratios and expected survival rates. Economic outcomes were estimated using a partitioned survival model. The costs and utilities were gathered from published sources. The threshold for willingness-to-pay (WTP) for a quality-adjusted life year (QALY) was set at three times China's per capita gross domestic product in 2022. Sensitivity analyses (SA) were performed to address uncertainties in the model. Results: Four phase III randomized controlled trials were included, evaluating the cost-effectiveness of four PD-1 inhibitors, camrelizumab, nivolumab, tislelizumab, and pembrolizumab, compared to chemotherapy for the second-line treatment of advanced or metastatic ESCC. For camrelizumab, nivolumab, tislelizumab, and pembrolizumab, the corresponding incremental cost-effectiveness ratios were $27,375.43/QALY, $205,312.19/QALY, $9,266.73/QALY, and $220,368.10/QALY, respectively. The SA results indicated the robustness of the base analysis findings. Conclusion: From the Chinese healthcare system, under the WTP of $38,253.48/QALY, tislelizumab is a cost-effective treatment option for the second-line treatment of advanced or metastatic ESCC. [ABSTRACT FROM AUTHOR]

This work was designed to assess the cost-effectiveness of front-line tislelizumab plus chemotherapy (TIS+Chemo) in advanced gastric cancer (GC) or gastroesophageal junction cancer (GEJC) with positive expression of programmed cell death ligand 1 (PD-L1) from the perspective of Chinese healthcare system. A 10-year partitioned survival model was undertaken utilizing clinical data from RATIONALE 305. Costs and utilities were both discounted at an annual rate of 5%. The primary outcome was incremental cost-effectiveness ratios (ICERs) and calculated as the cost per quality-adjusted life years (QALYs). The willingness-to-pay (WTP) threshold was set as $18,625/QALY. Only direct medical costs were considered. Sensitivity analyses and subgroup analyses were performed to evaluate the robustness of the model. In the base-case analysis, the incremental cost and effectiveness associated with TIS+Chemo vs Chemo was 7,361 and 0.38 QALYs, respectively, leading to an ICER of 19,371/QALY. At the WTP threshold of $18,625/QALY, the TIS+Chemo was not a cost-effective first-line treatment option. The model outcomes were robust. TIS+Chemo did not provide a cost-effective approach for PD-L1 positive advanced GC/GEJC in China setting. However, TIS+Chemo might be cost-effective in provinces with higher WTP threshold. RATIONALE 305, , identifier is NCT03777657. [ABSTRACT FROM AUTHOR]

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: 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. [ABSTRACT FROM AUTHOR]

Introduction: First-line treatment with tislelizumab plus chemotherapy has shown clinical benefits for patients with advanced or metastatic esophageal squamous cell carcinoma (OSCC) in China, while its economic burden is unknown. This study aimed to evaluate the cost-effectiveness of tislelizumab plus chemotherapy from the perspective of the Chinese healthcare system. Methods: We constructed a partitioned survival model to compare the costeffectiveness of tislelizumab plus chemotherapy with chemotherapy in patients with advanced OSCC. Patient characteristics and clinical outcomes were extracted from RATIONALE-306. Costs, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios (ICERs) were selected as the study outcomes. Sensitivity analysis and subgroup analysis were conducted to test the stability of the results. Results: Tislelizumab plus chemotherapy provided additional 0.48 QALYs with the incremental cost of $16,587.2 than chemotherapy, of which ICER was $34,699.72 per QALY. When the willingness-to-pay threshold was set as $37,260, the novel therapy had a probability of 77% to be cost-effective. Our base-case analysis results were sensitive to utilities of progression-free survival and progression of disease. Our subgroup analysis showed that the novel therapy was associated with cost-effectiveness in patients with a high expression of PD-L1. Conclusion: Tislelizumab plus chemotherapy was likely to be more costeffective compared with chemotherapy in the first-line therapy of advanced OSCC from the perspective of the Chinese healthcare system. Our findings can provide clinicians and decision-makers with evidence of the cost-effectiveness of tislelizumab. [ABSTRACT FROM AUTHOR]

Background: Tislelizumab, a humanized IgG4 anti-PD-1 monoclonal antibody has been approved in China and Europe. According to the published clinical research, tislelizumab shows satisfactory safety profile. No severe hepatotoxicity or acute kidney injury were reported. Case presentation: We presented a case study of a 74-year-old man who developed acute kidney injury (grade 3) and acute liver injury (grade 4) after being administered tislelizumab for the treatment of esophageal squamous cell carcinoma. We reviewed the patient's history, physical examination, and laboratory findings and provided comprehensive differentials of the possible causes of the toxicities. Immune Checkpoint Inhibitors (ICI) hepatotoxicity and nephrotoxicity were confirmed clinically. We also discussed the management of toxicities associated with ICIs and the need for a multidisciplinary approach to care. Conclusions: The case highlights the importance of close monitoring and prompt management of toxicities associated with ICIs and the need for further research to better understand the risk factors for these toxicities and to identify effective treatments for them. [ABSTRACT FROM AUTHOR]

Background: The combination of tislelizumab and gemcitabine plus cisplatin (GP) in the first‐line treatment of patients with recurrent or metastatic nasopharyngeal carcinoma (R/M NPC) has yielded significant results. However, it is not clear whether this treatment option is cost‐effective in China. The purpose of this study is to evaluate the cost‐effectiveness of tislelizumab plus GP for the first‐line treatment of R/M NPC from the perspective of the Chinese healthcare system. Methods: A partitioned survival model with three discrete health states was constructed to evaluate the cost‐effectiveness of tislelizumab plus GP versus GP in patients with R/M NPC. The target population enrolled in the RATIONALE‐309 trial had previously not treated for R/M NPC. Drug costs were obtained from relevant databases, and the remaining cost and health utility data were collected from the literature. The main outcomes include the expected life years, quality‐adjusted life years (QALYs), total cost, and incremental cost–benefit ratio (ICER). Results: The tislelizumab plus GP regimen produced an additional cost ($18392.76) and additional 1.57 QALYs compared with GP used alone. The ICER was $18392.75/QALYs. Sensitivity analysis showed that the analysis was robust and the utility of PD status was most sensitive to the model results. The possibility of tislelizumab plus GP being cost‐effective at the willingness‐to‐pay (WTP) threshold of $37 653/QALY was 99.8%. Subgroup analysis showed that high PD‐L1 expression had little impact on the ICER of this regimen. Conclusion: In patients with R/M NPC, the regimen of tislelizumab plus GP, as the first‐line treatment, is more cost‐effective than the GP regimen in China. [ABSTRACT FROM AUTHOR]

Introduction: The RATIONALE-309 trial confirmed the significant efficacy and safety of tislelizumab plus chemotherapy in patients with recurrent or metastatic nasopharyngeal carcinoma (R/M NPC). However, the economic benefits of this regimen are unclear. Therefore, this study aimed to evaluate the cost-effectiveness of adding tislelizumab to chemotherapy for R/M NPC from the perspective of the Chinese healthcare system. Methods: A Markov model was established to simulate the costs and outcomes of tislelizumab plus chemotherapy versus chemotherapy. The survival data came from the RATIONALE-309 trial. Only direct medical costs were considered, and utility values were referred to the literature. The incremental cost-effectiveness ratio (ICER) was used as the main outcome measure. Sensitivity analysis was performed to assess the effect of parameter uncertainty on the model. Additionally, subgroup analyses were performed. Results: The basic analysis showed that the cost of tislelizumab plus chemotherapy ($33,693) was $17,711 higher than that of chemotherapy ($15,982), but it also gained 1.05 QALYs more (2.72 QALYs vs. 1.67 QALYs), with an ICER of $16,859/QALY, which was lower than the willing-to-pay (WTP) of $36,289/QALY. The factors that most influenced the model were the utility of PD, the cost of tislelizumab, and the risk of platelet count decreased in tislelizumab plus chemotherapy group. The subgroup analysis also demonstrated that tislelizumab plus chemotherapy was cost-effective in the whole population regardless of EBV DNA level and PD-L1 expression level. Conclusion: Compared with chemotherapy alone, tislelizumab plus chemotherapy was cost-effective for the treatment of R/M NPC in China. [ABSTRACT FROM AUTHOR]

Objective of the study was to compare the cost-effectiveness of tislelizumab plus chemotherapy as first-line therapy for patients with advanced or metastatic esophageal squamous cell carcinoma (ESCC) versus chemotherapy alone.Methods: A partitioned survival model with three states was constructed based on the RATIONALE-306 trial. The model's time horizon was ten years, and its cycle was three weeks. Only direct medical costs were considered from the healthcare perspective in China. Calculations were performed on total costs, quality-adjusted life years (QALYs), and incremental cost-effectiveness ratios (ICERs). One-way sensitivity and probabilistic sensitivity analysis (PSA) were performed to determine the uncertainty regarding model parameters.Results: Tislelizumab plus chemotherapy provided 1.35 QALYs for $26,450.77, while chemotherapy alone provided 0.89 QALY for $16,687.15. Compared to chemotherapy alone, tislelizumab had an ICER of $21,062.09/QALY. At the threshold of three times the Chinese GDP per capita ($38,253/QALY), the PSA indicated that tislelizumab had a 96.4% likelihood of being designated cost-effective. At the threshold of 1.5 times the Chinese GDP per capita ($19,126.5/QALY), the PSA indicated that tislelizumab had a probability of 48.7% of being designated cost-effective.Conclusion: Tislelizumab plus chemotherapy as the first treatment for patients with advanced or metastatic ESCC may be a cost-effective option compared to chemotherapy alone at 3 times Chinese GDP per capita. [ABSTRACT FROM AUTHOR]

Objective: Domestic PD-1inhibitor tislelizumab has emerged as a promising treatment for Chinese patients with driver-negative advanced or metastatic non-small cell lung cancer (NSCLC). The purpose of our study to evaluate whether tislelizumab is cost-effective as a second- or third-line treatment for this population compared with docetaxel (conventional chemotherapy) and nivolumab (imported PD-1inhibitor), from the perspective of the Chinese healthcare system. Material and Methods: A Markov model with a 3-week Markov cycle and a 30-year time horizon was built to compare the cost-effectiveness of second- or third-line tislelizumab versus docetaxel and nivolumab. Transition probabilities, including disease progression, survival, and adverse events (AEs)-related treatment discontinuation event, were estimated from the clinical trials. Costs and health utilities were collected from local hospitals, public database and published literature. Results: Compared with docetaxel, tislelizumab provided an additional 0.33 quality-adjusted life-years (QALYs) (1.37 vs. 1.04 QALYs) at an incremental cost of $9,286 ($23,646 vs. $14,360) for Chinese patients with driver-negative advanced or metastatic NSCLC, resulting in an incremental cost-effectiveness ratio (ICER) of $27,959/QALY under the WTP threshold of $35,663/QALY used in the model. Compared with nivolumab, tislelizumab was associated with a lower cost ($23,646 vs. $59,447) and higher QALYs (1.37 vs. 1.20 QALYs), resulting in its dominance of nivolumab. Conclusion: From the perspective of the Chinese healthcare system, domestic PD-1inhibitor tislelizumab immunotherapy represents a cost-effective treatment strategy compared with conventional docetaxel chemotherapy and imported PD-1inhibitor nivolumab immunotherapy in the treatment of driver-negative advanced or metastatic NSCLC beyond the first-line setting. In the era of "Universal Medical Insurance System", the rational use of domestic anticancer drugs guided by cost-benefit evidence would be an effective means to balance the limited expenditure of medical insurance fund and the growing demand for cancer treatments. [ABSTRACT FROM AUTHOR]

Background: Tislelizumab, a new high-affinity programmed cell death protein-1 (PD-1) inhibitor, significantly prolonged the overall survival in pretreated non-small-cell lung cancer (NSCLC). This study aimed to assess the cost-effectiveness of tislelizumab versus docetaxel for this population in China. Methods: A three-state partitioned survival model was developed to simulate advanced NSCLC. Efficacy and safety data were based on a global phase 3 clinical trial (RATIONALE 303). Utilities were mainly extracted from previously published resources. Costs were calculated from the Chinese healthcare system's perspective, and only direct medical costs were covered. The main outcomes included total costs, life years (LYs), quality-adjusted life years (QALYs), and incremental cost effectiveness ratio (ICER). One-way and probabilistic sensitivity analyses were carried to test the uncertainty of the modeling results. In addition, several scenarios including tislelizumab price before negotiation, different docetaxel price calculation, 50-year time horizon, and alternative utility values were assessed. Results: The model predicted an average gain of 0.62 LYs and 0.51 QALY for tislelizumab vs. docetaxel, at the additional cost of $9,219. The resulting ICER was $15,033.92/LY and $18,122.04/QALY, both below the cost-effective threshold (CET) of three times gross domestic product (GDP) per capita in China. Sensitivity analyses showed that the results are robust over a plausible range for majority of inputs. Utility of progression-free survival (PFS), followed by the price of tislelizumab, had the greatest impact on the ICER. The probability of being cost-effective for tislelizumab was 96.79% at the CET we set. Conclusion: Tislelizumab improves survival, increases QALYs, and can be considered a cost-effective option at current price compared with docetaxel for pretreated advanced NSCLC in China. [ABSTRACT FROM AUTHOR]

Background: Tislelizumab combined with chemotherapy has shown significant clinical benefits in improving overall survival compared to chemotherapy alone for patients with extensive-stage small-cell lung cancer (ES-SCLC)., Aim: This study aimed to evaluate the cost-effectiveness of tislelizumab plus chemotherapy versus standard chemotherapy as a first-line treatment for ES-SCLC from the US payer perspective and the perspective of the Chinese healthcare system., Method: We conducted an economic evaluation using a Markov state-transition model, reflecting the US payer perspective and the perspective of the Chinese healthcare system. Baseline patient characteristics and essential clinical data were obtained from the RATIONALE-312 trial. The costs and utilities were derived from open-access databases and published literature. The primary outcomes measured included quality-adjusted life years (QALYs), incremental cost-effectiveness ratio (ICER), incremental net health benefit (INHB), and incremental net monetary benefit (INMB). Uncertainties in the model were addressed by probabilistic sensitivity analysis (PSA) and one-way sensitivity analysis (OWSA)., Results: In the base-case analysis, the addition of tislelizumab to chemotherapy provided an incremental gain of 0.16 QALYs at an additional cost of $7430.73, resulting in an ICER of $46,132.33 per QALY. Although above the willingness-to-pay (WTP) threshold of China of $38,042.49 per QALY, the cost-effectiveness was marginal, with an INHB of - 0.03 QALYs and an INMB of $- 1303.06. In the US, despite a slightly higher effectiveness gain of 0.28 QALYs, the increased cost of $45,157.35 resulted in an unfavorable ICER of $163,885.06 per QALY, exceeding the US WTP threshold of $150,000.00. PSA showed probabilities of cost-effectiveness of tislelizumab plus chemotherapy at 17.18% in China and 40.41% in the US., Conclusion: Tislelizumab combined with chemotherapy was not a cost-effective first-line treatment option for ES-SCLC in China or the US; however, the margin of cost-effectiveness was narrow., Competing Interests: Conflicts of interest The authors declare that they have no conflicts of interest., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

The RATIONALE-306 study revealed that patients with advanced or metastatic oesophageal squamous cell carcinoma (OSCC) could benefit from treatment with tislelizumab plus chemotherapy. This study aimed to evaluate the cost-effectiveness of tislelizumab plus chemotherapy for treating OSCC from the perspective of the Chinese healthcare system. Partitioned survival model estimated the cost-effectiveness of tislelizumab plus chemotherapy compared with chemotherapy alone for treating OSCC using RATIONALE-306 data. Costs and utilities were obtained from local databases and published studies. Costs, quality-adjusted life-years (QALYs), life-years, incremental cost-effectiveness ratios (ICER), incremental net health benefits (INHB), and incremental net monetary benefits (INMB) were outcomes. Price simulation were conducted at the willingness-to-pay (WTP) threshold. Sensitivity and subgroup analyses were performed to assess model robustness. Compared with chemotherapy alone, tislelizumab plus chemotherapy yielded an ICER of USD 27,896/QALY, gained an additional 0.414 QALYs and 0.751 life-years, and increased the cost by USD 11,560. Probabilistic sensitivity analysis revealed that tislelizumab plus chemotherapy was cost-effective at the WTP of USD 38,258/QALY with probability of 94.43%. When the price in China was less than USD 3.714 per mg, the price simulation results indicated that tislelizumab plus chemotherapy was cost-effective at a WTP threshold of USD 38,258. Tislelizumab plus chemotherapy yielded an INHB of 0.112 QALYs and an INMB of USD 4,279 compared with chemotherapy alone at a WTP threshold of USD 38,258. Based on the sensitivity analyses, the above results were stable. A general trend was observed for subgroups with better survival benefits related to a higher probability of cost-effectiveness. From the Chinese healthcare perspective, tislelizumab plus chemotherapy is more cost-effective than chemotherapy alone as a first-line therapy for OSCC. These findings can help clinicians make optimal clinical decisions and assist decision-makers in evaluating the cost-effectiveness of tislelizumab in clinical practice., (© 2024. The Author(s).)

Background: Tislelizumab is the first PD-1 inhibitor in China to demonstrate superior efficacy in second-line or third-line treatment of patients with advanced or metastatic non-small-cell lung cancer (NSCLC). This study aimed to evaluate the cost-effectiveness of tislelizumab compared to docetaxel from a Chinese healthcare system perspective., Methods: A dynamic Markov model was developed to evaluate the cost-effectiveness of tislelizumab in comparison to docetaxel in second or third-line treatment. The efficacy data utilized in the model were derived from the RATIONALE-303 clinical trial, while cost and utility values were obtained from the drug data service platform and published studies. The primary outcomes of the model encompassed quality-adjusted life years (QALYs), costs, and incremental cost-effectiveness ratios (ICERs). One-way sensitivity analysis and probabilistic sensitivity analysis were conducted to validate the robustness of the base case analysis results., Results: The tislelizumab group demonstrated a cost increase of CNY 117,473 and a gain of 0.58 QALYs compared to the docetaxel group, resulting in an ICER value of CNY 202,927 per QALY gained., Conclusion: The administration of tislelizumab in patients with advanced or metastatic NSCLC not only extends the progression-free survival (PFS) and overall survival (OS). Moreover, this treatment demonstrates a favorable cost-effectiveness profile across the Chinese population., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Zhang, Fan, Zhang, Jiang, Wu, Yang, Li and Liu.)

• Patient characteristics were associated with treatment patterns in HCC. • Tislelizumab, camrelizumab, and tislelizumab + TACE had similar effectiveness in advanced HCC. • PVTT was an independent risk factor for PFS in advanced HCC patients. Programmed cell death protein-1 (PD-1) inhibitors have shown promising clinical efficacy in treating advanced hepatocellular carcinoma (HCC). However, little evidence exists regarding their treatment patterns and outcomes in real-world practice in China. This study aimed to investigate real-world treatment patterns and outcomes of PD-1 inhibitors as first-line therapies for patients with advanced HCC in China. The study population included adult patients with advanced HCC who were initially treated with PD-1 inhibitors from April 2020 to November 2022 in China. Descriptive statistics were used to report first-line treatment patterns and associations between patient characteristics and the most frequently used treatment patterns. The effectiveness of first-line treatment with PD-1 inhibitors was also evaluated according to survival and tumor response. The analyses enrolled 480 patients. The four most frequently used first-line treatment patterns of camrelizumab, tislelizumab, camrelizumab + TACE, and tislelizumab + TACE showed statistical differences in patient characteristics of gender, HBV infection, liver cirrhosis, BCLC stage, and portal vein tumor thrombus (all P < 0.05). However, there was no significant difference in median progression-free survival among the first-line treatments of tislelizumab, camrelizumab, and tislelizumab + TACE (not reached vs. 4.4 months vs. 3.6 months, P = 0.5178). The three groups had similar objective response rates (25.0 % vs. 28.6 % vs. 28.6 %, P = 0.927), and disease control rates (73.1 % vs. 78.6 % vs. 64.3 %, P = 0.573) with no statistical significance. Our findings provided insights into potential therapeutic strategies of PD-1 inhibitors in first-line settings for advanced HCC in real-world practice in China. It was recommended to consider patient characteristics associated with therapeutic options when making clinical decisions. Prospective randomized controlled studies with larger sample sizes and longer follow-up times were warranted further to verify the potential clinical benefits of PD-1 inhibitors. [ABSTRACT FROM AUTHOR]

Blocking of the interaction between Programmed cell death 1 (PD-1) and its ligand PD-L1 by monoclonal antibodies has elicited unprecedented therapeutic benefits and achieved a major breakthrough in immunotherapy of multiple types of tumors. Here, we determined the crystal structure of PD-1 in complex with the Fab fragment of tislelizumab. This monoclonal antibody was approved in December 2019 by the China National Medical Product Administration for Hodgkin's lymphoma and is under multiple clinical trials in China and the US. While the three complementarity determining regions (CDRs) in the light chain are involved in the target interaction, only CDR3 within the heavy chain interacts with PD-1. Tislelizumab binds the front β-sheet of PD-1 in a very similar way as PD-L1 binds to PD-1, thereby blocking the PD-1/PD-L1 interaction with a higher affinity. A comparative analysis of PD-1 interactions with therapeutic antibodies targeting PD-1 provides a better understanding of the blockade mechanism of PD-1/PD-L1 interaction in addition to useful information for the improvement of therapeutic antibodies capable of diminishing checkpoint signaling for cancer immunotherapy. • The crystal structure of the PD-1/tislelizumab complex was determined. • Tislelizumab blocks the PD-1/PD-L1 interaction by mimicking the PD-L1 binding on PD-1. • Tislelizumab binding does not involve the flexible loops of PD-1, unlike other antibodies. [ABSTRACT FROM AUTHOR]

Background: The promising therapeutic outcomes of neoadjuvant immunotherapy combined with chemotherapy in the treatment of locally advanced esophageal squamous cell carcinoma (ESCC) have been confirmed by several phase II clinical trials and have been widely demonstrated in clinical work. Theoretically, postoperative adjuvant immunotherapy may further improve the therapeutic effect, but there is still lack of evidence. The aim of this study was to analyse the safety and efficacy of perioperative immunotherapy (tislelizumab) in locally advanced resectable thoracic ESCC (PILOT trial)., Methods: Seventy-three eligible patients with pathologically confirmed thoracic ESCC of clinical T1b-3N1-3M0 or T3N0M0 stage were allocated to receive neoadjuvant immunotherapy (tislelizumab 200 mg d1, q3w × 2 cycles) plus chemotherapy (nad-paclitaxel 260 mg/m 2 d1 + carboplatin AUC = 5 d1, q3w × 2 cycles) treatment. Patients with pathologic complete response (pCR) after esophagectomy received adjuvant tislelizumab (200 mg every 3 weeks for up to one year), and patients with non-pCR were assigned adjuvant tislelizumab plus chemotherapy for two cycles and then maintenance tislelizumab (200 mg every 3 weeks for up to 15 cycles). The primary endpoint of this study is 2-year disease-free survival (DFS) in non-pCR patients. The secondary endpoints include pCR rate, major pathological response rate, 2-year DFS in pCR patients, R0 resection rate, adverse events, and overall survival., Discussion: This protocol was reviewed and approved by the Ethics Committee of Shanghai Chest Hospital (IS23059). This is the first prospective clinical trial to investigate the safety and efficacy of perioperative immunotherapy for locally advanced resectable thoracic ESCC. We hypothesize that perioperative immunotherapy could be a promising therapeutic strategy that can provide better 2-year DFS in non-pCR patients., Trial Registration: ClinicalTrial.gov: NCT0605633., (© 2023. The Author(s).)

The utilization of immune checkpoint inhibitors in oncological treatment has increased in recent years. The therapeutic strategy of targeting the programmed death-1 (PD-1)/programmed death-ligand 1 (PD-L1) pathway has altered the management of advanced non-small cell lung carcinoma (NSCLC). Tislelizumab, a novel anti-PD-1 monoclonal antibody developed in China, has demonstrated efficacy in treating advanced NSCLC. However, its potential role as a neoadjuvant therapy for locally advanced NSCLC has not been definitively established. Current guidelines do not specify which patient populations may gain the most benefit from neoadjuvant immunotherapy coupled with chemotherapy, nor do they indicate the optimal timing, dose or duration of adjuvant maintenance therapy post-NSCLC surgery. Similarly, data concerning the safety and practicability of surgical resection following neoadjuvant tislelizumab treatment for NSCLC remain limited. The present study describes the case of a patient diagnosed with stage IIIB NSCLC, which was initially deemed unresectable. A preoperative biopsy of the tumor mass revealed squamous cell carcinoma and a negative PD-L1 gene test. Notably, after two cycles of neoadjuvant tislelizumab treatment coupled with chemotherapy, the tumor exhibited marked shrinkage. This permitted the patient to undergo thoracoscopic radical lung cancer resection, which resulted in a pathological complete response. Postoperative pathology identified a large infiltration of lymphoplasmacytic cells and foamy histiocytes. The patient experienced grade 2 myelosuppression, a condition that was successfully addressed with the administration of recombinant human granulocyte colony-stimulating factor. The present case indicates the safety and feasibility of neoadjuvant immunotherapy integrated with chemotherapy for patients with locally advanced, PD-L1-negative NSCLC prior to surgical intervention. Moreover, the case suggests the potential of this therapeutic combination to alter the tumor microenvironment. However, the generalization of these findings necessitates further validation through randomized multicenter trials. [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]

Objectives: This phase 2 study explored tislelizumab, an anti-PD-1 antibody, in combination with platinum-based chemotherapy as first-line treatment of advanced lung cancer., Material and Methods: Eligible patients had histologically/cytologically confirmed advanced/metastatic nonsquamous non-small cell lung cancer (NSQ), squamous NSCLC (SQ), or extensive-stage small cell lung cancer (SCLC). All patients received tislelizumab 200 mg in combination with 4-6 cycles of platinum-doublet. The NSQ cohort received pemetrexed + platinum Q3W for 4 cycles followed by pemetrexed maintenance, the SQ cohort received paclitaxel + platinum (A) or gemcitabine + platinum (B) Q3W, and the SCLC cohort received etoposide + platinum Q3W. The primary endpoint was investigator-assessed objective response rate (ORR) per RECIST v1.1. Progression-free survival (PFS) and tolerability profile were secondary endpoints; exploratory endpoints included overall survival (OS) and predictive biomarkers., Results: Fifty-four patients (NSQ, n = 16; SQ = 21 [SQ-A, n = 15; SQ-B, n = 6]; SCLC, n = 17) were enrolled; as of February 25, 2019, 14 remained on treatment. Confirmed ORRs were 44% (NSQ), 80% (SQ-A), 67% (SQ-B), and 77% (SCLC). Median PFS were 9.0 months (NSQ), 7.0 months (SQ-A), and 6.9 months (SCLC); PFS in SQ-B are not mature. Median OS was not reached in all cohorts except for SCLC (15.6 months). Common treatment-emergent AEs included anemia (79.6%, n = 43) and decreased white blood cell count (74.1%, n = 40). Gene expression analyses revealed distinct patterns by histology type; lower tumor inflammation signature levels were observed among nonresponding patients with NSQ and SCLC., Conclusions: Tislelizumab plus chemotherapy demonstrated encouraging antitumor activity, was generally well tolerated, and distinct immune- and cell cycle-related gene signatures were associated with efficacy across cohorts., (Copyright © 2020 The Author(s). Published by Elsevier B.V. All rights reserved.)