Search

Background: Malignant esophageal mediastinal fistula is a severe complication that occurs in both the advanced stages of esophageal cancer and after radiotherapy for esophageal cancer. Esophageal mediastinal fistula is very susceptible to complications such as mediastinitis and mediastinal abscess, resulting in a significantly elevated mortality rate for patients. We reported a rare case of esophageal mediastinal fistula after immunotherapy for non-small cell lung cancer (NSCLC)., Case Presentation: A 74-year-old male patient with NSCLC was hospitalized in July 2023. About one week after Tislelizumab immunotherapy, the patient suddenly developed high fever accompanied by coughing and choking on water, chest tightness, shortness of breath, and hemoptysis. Following the completion of bronchial artery computed tomography angiography (CTA), imaging suggested the presence of esophageal mediastinal fistula. We opted for a conservative medical treatment instead of surgery. The patient was discharged without any complications., Conclusions: This is the first case of NSCLC accompanied by an esophageal mediastinal fistula after treatment with tislelizumab. The occurrence of malignant esophageal mediastinal fistula is very uncommon and poses a high level of hazard. In addition, this paper provides a concise overview of cases of lung cancer complicated with esophageal fistula in the past 10 years. It offers valuable insights for diagnosis and treatment, serving as a resource for clinicians., Competing Interests: Declarations. Ethics approval and consent to participate: The protocol for this study was examined by the Ethics Committee of the First Affiliated Hospital of Zhejiang University School of Medicine. The participants expressed full knowledge of this report and signed an informed consent form, agreeing to publicly publish their personal clinical data, but not for any other purposes. Consent for publication: Written informed consent was obtained from the patient for publication of this case report and any accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Background: Since the imported PD-1 inhibitor pembrolizumab was listed in China in 2018, China has opened up the era of immunotherapy for malignant tumors, with several domestically produced PD-1 inhibitors coming onto the market one after another. To find out whether there are differences in the efficacy and safety of domestic and imported PD-1 inhibitors in patients with advanced non-small cell lung cancer, we conducted this retrospective study in two tertiary hospitals in China., Methods: Patients with advanced NSCLC treated with tislelizumab or camrelizumab or pembrolizumab who met the inclusion criteria were screened through the electronic medical record system. A total of 259 patients were screened, but due to the unbalanced baseline, we performed propensity score matching and finally included 149 patients in three groups: pembrolizumab (n = 38), tislelizumab (n = 38), and camrelizumab (n = 73), which had very balanced baseline characteristics in each group after propensity score matching treatment., Results: The results showed that the median progression-free period was 11.3 m vs 10.1 m vs 8.9 m; p = 0.754; and the objective response rate was 63.2% vs 50% vs 57.5%; P = 0.510 for pembrolizumab, tislelizumab, and carrelizumab, respectively. There was no significant difference in median PFS between PD-L1 expression subgroups. In terms of safety, only skin toxicity of any grade of carrelizumab was higher than that of the other two groups (p = 0.034), and the incidence of grade ≥ 3 adverse reactions was not statistically significant among the three groups., Conclusion: In this real-world study, the efficacy and safety of the domestically produced tislelizumab, camrelizumab, and the imported pembrolizumab were comparable., Competing Interests: Declarations. Conflict of interest: All the authors declare that they have no conflict of interest. Ethical approval: The study was approved by the Ethical Review Committee of the First Hospital of Guangdong Pharmaceutical University., (© 2024. The Author(s), under exclusive licence to Federación de Sociedades Españolas de Oncología (FESEO).)

The Phase 3 RATIONALE-312 trial (NCT04005716) showed that tislelizumab plus chemotherapy led to a noteworthy enhancement resulted in a significant improvement in overall survival among patients diagnosed with extensive-stage small-cell lung cancer (ES-SCLC) compared to chemotherapy alone. The treatment also had an acceptable level of safety. Nevertheless, the debate over the efficacy of implementing several treatment plans in competition continues due to the significant expenses involved. Therefore, we aimed to evaluate the potential efficacy and cost of tislelizumab treatment as a first-line treatment for the ES-SCLC patient population in China. The study assessed primary health outcomes by measuring life years (LYs), quality-adjusted life years (QALYs), and incremental cost-effectiveness ratios (ICERs). This was done using a Markov model considering three health states with a 15-year horizon. To assess its model resilience, we conducted one-way sensitivity analyses with probability. In addition, subgroup analyses of some pre-specified patients was performed. Compared to chemotherapy alone, tislelizumab plus chemotherapy resulted in an additional 0.34 ($8,028) QALYs, leading to an ICER of $23,553 per QALY for the overall patient population. The ICER was lower than the assumed willingness-to-pay threshold of $35,367 per QALY. Approximately 60% of simulations suggested that tislelizumab in combination with chemotherapy was cost-effective, while 40% suggested that chemotherapy alone was cost-effective. The subsequent sensitivity analyses revealed that the health utility value associated with the disease progression parameter had the greatest influence on ICER. Tislelizumab plus chemotherapy was a preferable treatment option for regimens for patients with ES-SCLC in China. This finding is important in guiding the Chinese healthcare system., Competing Interests: Declarations. Competing interests: The authors declare no competing interests. Ethics approval and consent to participate: All the data included in this analysis were derived from published literature and public data. No patient-identifiable data were applied or used. Therefore, the approval of the independent ethics committee was not required., (© 2024. The Author(s).)

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.)

Purpose: First-line tislelizumab plus chemotherapy significantly improved progression-free survival (PFS) versus chemotherapy alone in advanced squamous non-small-cell lung cancer (sq-NSCLC) at the interim analysis of the phase III RATIONALE-307 trial. We present the final analysis of this trial., Patients and Methods: Patients with treatment-naive, stage IIIB/IV, sq-NSCLC were randomized (1 : 1: 1) to 21-day cycles of i.v.: tislelizumab plus paclitaxel and carboplatin (arm A); tislelizumab plus nab-paclitaxel and carboplatin (arm B); or paclitaxel and carboplatin (arm C). The primary endpoint was independent review committee-assessed PFS; overall survival was a secondary endpoint., Results: In total, 360 patients were randomized; 355 received treatment. At the final analysis (median study follow-up: 16.7 months), tislelizumab plus chemotherapy had a manageable safety profile, consistent with that at the interim analysis. Improvement in PFS was maintained for arms A and B versus C {hazard ratio (HR) 0.45 [95% confidence interval (CI) 0.33-0.62] and 0.43 (95% CI 0.31-0.60), respectively}. Overall survival HRs for arms A and B versus C were 0.68 (95% CI 0.46-1.01) and 0.75 (95% CI 0.50-1.12), respectively., Conclusions: The RATIONALE-307 final analysis demonstrated superior clinical benefit with addition of tislelizumab to chemotherapy, and a manageable safety profile, as first-line treatment of advanced sq-NSCLC., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: The purpose of this study was to report an updated, final analysis with longer follow-up for the open-label phase III RATIONALE-304 study of first-line tislelizumab plus chemotherapy versus chemotherapy alone for advanced nonsquamous non-small-cell lung cancer (nsq-NSCLC)., Materials and Methods: Patients with histologically confirmed stage IIIB/IV nsq-NSCLC were randomized (2 : 1) to 4-6 cycles of tislelizumab plus platinum-based chemotherapy and pemetrexed every 3 weeks, followed by maintenance tislelizumab and pemetrexed, or platinum-based chemotherapy and pemetrexed alone every 3 weeks followed by maintenance pemetrexed. The primary endpoint was independent review committee (IRC)-assessed progression-free survival (PFS IRC ). Overall survival (OS), safety, and tolerability were secondary endpoints., Results: Overall, 334 patients were randomized (tislelizumab plus chemotherapy: n = 223; chemotherapy: n = 111). At final analysis (median follow-up 16.1 months), safety/tolerability profiles in both arms were consistent with the interim analysis. Tislelizumab plus chemotherapy continued to demonstrate prolongation of PFS IRC versus chemotherapy alone {stratified hazard ratio (HR) 0.63 [95% confidence interval (CI) 0.47-0.86]; median PFS IRC 9.8 months (95% CI 8.9-11.7 months) versus 7.6 months (95% CI 5.6-8.0 months), respectively}. OS stratified HR for tislelizumab plus chemotherapy versus chemotherapy was 0.90 (95% CI 0.63-1.28), with median OS of 21.4 months (95% CI 17.7 months-not estimable) versus 21.3 months (95% CI 15.6 months-not estimable), respectively. At a subsequent ad hoc analysis (median follow-up 19.3 months), OS HR between arms was 0.85 (95% CI 0.63-1.14); when adjusted for crossover using the two-stage method, the OS HR was 0.68 (95% CI 0.48-0.96)., Conclusions: After longer follow-up, first-line tislelizumab plus chemotherapy continued to demonstrate a manageable safety profile and a favorable PFS benefit over chemotherapy alone in patients with advanced/metastatic nsq-NSCLC., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

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.)

Introduction: Extensive-stage SCLC (ES-SCLC) prognosis remains poor. The phase 3 RATIONALE-312 study aimed to evaluate the efficacy and safety of tislelizumab plus chemotherapy as first-line treatment for ES-SCLC., Methods: RATIONALE-312 is a randomized, double-blind, placebo-controlled trial, conducted in the People's Republic of China. Eligible patients with previously untreated ES-SCLC were randomized 1:1 to receive four cycles of tislelizumab 200 mg or placebo, with etoposide plus carboplatin or cisplatin intravenously every 3 weeks, followed by tislelizumab 200 mg or placebo as maintenance. The primary end point was overall survival (OS). Secondary end points included progression-free survival and safety., Results: Between July 22, 2019 and April 21, 2021, 457 patients were randomized to tislelizumab (n = 227) or placebo (n = 230), plus chemotherapy. Baseline demographics were generally balanced between arms. At the data cutoff (April 19, 2023), the median study follow-up was 14.2 months (interquartile range: 8.6-25.3). Tislelizumab plus chemotherapy exhibited a statistically significant OS benefit versus placebo plus chemotherapy (stratified hazard ratio = 0.75 [95% confidence interval (CI): 0.61-0.93]; one-sided p = 0.0040; median: 15.5 [95% CI: 13.5-17.1] versus 13.5 mo [95% CI: 12.1-14.9], respectively). Progression-free survival was significantly improved in the tislelizumab versus placebo arm (stratified hazard ratio = 0.64 [95% CI: 0.52-0.78]; p < 0.0001; median: 4.7 [95% CI: 4.3-5.5] versus 4.3 mo [95% CI: 4.2-4.4], respectively). Grade greater than or equal to 3 treatment-related adverse events were reported in 86% of patients in each treatment arm and were mostly hematologic., Conclusions: Tislelizumab plus chemotherapy exhibited statistically significant clinical benefit and manageable safety compared with placebo plus chemotherapy as first-line treatment in patients with advanced ES-SCLC., Competing Interests: Disclosure Dr. Zhao reports receiving payment or honoraria for lectures, presentations, speaker bureaus, manuscript writing, or educational events from Roche, AstraZeneca, Merck Sharp & Dohme, Novartis, and Eli Lilly. Drs. Qin and Zheng are employees of BeiGene (Beijing) Co., Ltd. and have stock or stock options with BeiGene (Beijing) Co., Ltd. Dr. Leaw and Ms. Chen are employees of BeiGene (Shanghai) Co., Ltd. and have stock or stock options with BeiGene (Shanghai) Co., Ltd. The remaining authors declare no conflict of interest., (Copyright © 2024 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.)

Background: Targeted therapy with combined dabrafenib and trametinib has been proven to provide clinical benefits in patients with BRAF V600E mutation-positive NSCLC. Nevertheless, the treatment strategy for NSCLC patients with BRAF non-V600E mutations remains limited., Case Presentation: Here, we present a NSCLC patient with a BRAF N581S mutation, which is a class III BRAF mutation, and this patient had a durable response to targeted therapy with combined anlotinib and tislelizumab., Conclusion: We hope to bring more attention to rare non-V600 BRAF mutations by presenting this case of NSCLC., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflict of interest., (Copyright © 2024 Elsevier GmbH. All rights reserved.)

Background: The standard care for resectable non-small cell lung cancer (NSCLC) involves perioperative therapy combining chemotherapy and immune checkpoint inhibitors, typically lasting 6 to 12 months. However, the optimal treatment strategies for potentially resectable squamous cell lung carcinoma (SCC) remain unclear. This Phase 2 trial aimed to assess the efficacy and safety of a condensed four-cycle perioperative treatment regimen with tislelizumab combined with chemotherapy in patients with potentially resectable stage III SCC., Methods: Patients with potentially resectable stage IIIA-IIIB (N2) SCC received intravenous tislelizumab, albumin-bound paclitaxel, and carboplatin for up to four cycles. The primary endpoints were major pathologic response (MPR) and incidence of treatment-related adverse events. Safety and potential biomarkers for efficacy prediction were also assessed., Results: Among 35 enrolled patients, 32 underwent surgery with R0 resection achieved in all cases. MPR was achieved in 24 patients and pathological complete response (pCR) in 14 patients. Radiographic objective response was observed in 31 patients. The 12-month and 24-month event-free survival rate was 85.7 and 61.0%, respectively. Four patients experienced grade 3 or 4 adverse events. Tumor tissue based next-generation sequencing revealed the potential associations between several biomarkers and pathological response, including tumor neoantigen burden score, 18-gene expression profile score, CD8 + T cells, M1/M2 macrophages ratio and interferon-gamma expression level. Besides, circulating tumor DNA (ctDNA) dynamics and concentration were also associated with pathological response and the presence of ctDNA at postoperative month 1 was a strong predictor for disease relapse. Furthermore, metagenomic sequencing in bronchoalveolar lavage fluid demonstrated Streptococcus was the most abundant genus in the pCR group., Conclusions: A condensed four-cycle perioperative treatment regimen of tislelizumab combined with chemotherapy demonstrated promising efficacy and manageable toxicities in potentially resectable stage III SCC. Specific biomarkers showed potential for predicting treatment efficacy and the mechanism of superior antitumor response of pCR patients was preliminarily and indirectly explored., Trial Registration: ClinicalTrials.gov, NCT05024266. Registered August 27, 2021., (© 2024. The Author(s).)

Cytokine release syndrome (CRS) is an uncommon but deadly side effect of immune checkpoint inhibitors (ICIs). ICIs are presently an increasingly important therapy option for malignant tumors, but there are limited treatments available for CRS. We present a case of a 72-year-old man who received one cycle of ICI coupled with cisplatin and albumin-binding paclitaxel therapy for a locally advanced right lung adenocarcinoma. Following an abrupt onset of dyspnea, the patient underwent a quick physical examination, blood tests and was diagnosed with CRS. After prompt initiation of glucocorticoid pulse treatment, the symptoms relieved. The case illustrates the management of severe CRS following ICI therapy while highlighting the uncommon and potentially fatal immune-related side effects.

Objective: This study evaluates the cost-effectiveness of tislelizumab plus chemotherapy as a first-line treatment for locally advanced or metastatic (IIIB/IV) nonsquamous non-small cell lung cancer (nsq-NSCLC) in China., Methods: A Markov model projected health outcomes and costs over a lifetime, with health states including progression-free survival, progressive disease, terminal progressive disease (TPD) and death. Data came from a Chinese phase III trial. The primary outcome was quality-adjusted life years (QALYs), with incremental cost-effectiveness ratios (ICERs) calculated. Using sensitivity analysis to confirm the robustness of the results., Results: The base-case analysis showed that tislelizumab combined chemotherapy group had 1.06 more QALYs (3.967 QALYs VS 2.909 QALYs) than the chemotherapy-alone group at an incremental cost of U.S. dollars ($) 19594.75 ($43390.52 VS $23795.77), resulting in an ICER of $18,512.47/QALY. This ICER is below the willingness-to-pay (WTP) threshold of three times China's 2023 per capita GDP ($36,672.23/QALY), indicating tislelizumab is economically favorable., Conclusion: The conclusion is that tislelizumab combination therapy is a cost-effective first-line treatment option for nsq-NSCLC patients in China.

The RATIONALE-307 study (ClinicalTrials.gov: NCT03594747) demonstrates prolonged progression-free survival (PFS) with first-line tislelizumab plus chemotherapy versus chemotherapy in advanced lung squamous cell carcinoma (LUSC; N = 360). Here we describe an immune-related gene expression signature (GES), composed of genes involved in both innate and adaptive immunity, that appears to differentiate tislelizumab plus chemotherapy PFS benefit versus chemotherapy. In contrast, a tislelizumab plus chemotherapy PFS benefit is observed regardless of programmed death ligand 1 (PD-L1) expression or tumor mutational burden (TMB). Genetic analysis reveals that NRF2 pathway activation is enriched in PD-L1 positive and TMB high patients. NRF2 pathway activation is negatively associated with PFS, which affects efficacy outcomes associated with PD-L1 and TMB status, impairing their predictive potential. Mechanistic studies demonstrate that NRF2 directly mediates PD-L1 constitutive expression independent of adaptive PD-L1 regulation in LUSC. In summary, the GES is an immune signature that might identify LUSC patients likely to benefit from first-line tislelizumab plus chemotherapy., Competing Interests: Declaration of interests S. Lu has received research support from AstraZeneca, BeiGene, BMS, Hansoh, Hengrui, Hutchison MediPharma, and Roche; received speaker fees from AstraZeneca, Hansoh, Hengrui Therapeutics, and Roche; and is an advisor and consultant of AstraZeneca, Boehringer Ingelheim, GenomiCare, Hutchison MediPharma, InventisBio Co. Ltd., Menarini, Pfizer, PriME Oncology, Roche, Simcere, Yuhan Corporation, and ZaiLab. Y.Z., L.L., Y.H., R.H., X.M., S. Leaw., F.B., and Z.S. are employees and stockholders of BeiGene, Ltd., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Tislelizumab is an anti-programmed death-1 (PD-1) monoclonal antibody with a construction that enables it to have a higher affinity to its target. We aimed to evaluate tislelizumab's safety and efficacy for treating non-small cell lung cancer (NSCLC)., Methods: Embase, Scopus, PubMed, Web of Science, and Google Scholar were searched up to December 20, 2022. The review only included randomized controlled trials (RCTs) that evaluated the safety or efficacy of tislelizumab for treating patients with lung cancer. The revised Cochrane risk-of-bias tool (RoB2) was utilized to evaluate study quality., Results: There were four RCTs identified, which included 1565 patients with confirmed locally advanced or metastatic squamous and/or non-squamous types of NSCLC. Treatment with tislelizumab was associated with better progression-free survival (PFS) and objective response rate (ORR), particularly when used in combination with chemotherapy. Almost all patients in both arms reported at least one treatment-emergent adverse event (TEAE). Decreased hematologic indexes accounted for more than 20% of the grade ≥ 3 TEAEs in the tislelizumab plus chemotherapy group. The proportion of TEAE that led to death in the tislelizumab plus chemotherapy arms ranged from 3.2 to 4.2%. Hypothyroidism, pneumonitis, and hyperglycemia were the most frequently noted immune-mediated adverse events in the tislelizumab group., Conclusions: Tislelizumab, whether used alone or in combination with chemotherapy, seems to demonstrate both a safety and efficacy as a treatment for NSCLC., (© 2023. The Author(s).)

Background: Immune checkpoint inhibitor (ICI)-associated cardiotoxicity is a relatively uncommon immune-related adverse effects (irAEs) with a high mortality rate. There are few recommendations for the replacement of different immune checkpoint inhibitors in domestic and international reports., Case Presentation: We report a case of a patient with squamous non-small cell lung carcinoma (squamous NSCLC) who developed cardiotoxicity after being treated with a programmed death-1 (PD-1) inhibitor and then changed to a PD-L1 inhibitor to continue the treatment. A significant benefit was observed after four cycles of immunotherapy, and no further cardiotoxicity occurred after the treatment was started., Conclusion: This case demonstrates that myocardial damage induced by tislelizumab (PD-1 inhibitor) can be improved after switching to sugemalimab (PD-L1 inhibitor) and that antitumor immunotherapy is effective. This result may have important implications for optimizing immunotherapy management regimens in cancer patients., 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 © 2023 Wu, Li, Cui and Zhang.)

Immune checkpoint inhibitors (ICIs) are an integral antitumor therapy for many malignancies. Most patients show very good tolerability to ICIs; however, serious immune-related adverse events (irAEs) with ICIs have been well documented and prevent some patients from continuing ICIs or even become the direct cause of patient death. Cytopenia is a rare irAE but can be life-threatening. Here, we present the case of a 66-year-old male patient with metastatic lung adenocarcinoma who received two doses of chemotherapy + PD-1 antibody tislelizumab and developed pancytopenia after each dose. Although the first episode of pancytopenia resolved with a treatment regimen of granulocyte colony-stimulating factor (G-CSF), thrombopoietin (TPO), and red blood cell and platelet transfusion, the second episode showed extreme resistance to these treatments and improved only after the administration of steroids. His second pancytopenia episode resolved after a long course of treatment with methylprednisolone, G-CSF, TPO, hetrombopag and multiple red blood cell and platelet transfusions. However, he suffered a cerebral infarction when his platelet count was in the normal range and gradually recovered 1 week later. This case highlights the importance of the early recognition and management of hematological irAEs., 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 © 2023 Gu, Zhao, Wang, Meng, Zhu, Wang, Zheng and Wu.)

Esophageal neuroendocrine carcinoma (ENEC) is an extremely rare tumor with highly malignant potential, rapid growth, and a poor prognosis. Advanced extrapulmonary neuroendocrine carcinoma should be treated with chemotherapeutic regimens suitable for small cell lung cancer. However, ENEC has no clear second-line treatment options. The clinical application of immunotherapy and targeted therapy in small cell lung cancer has produced good therapeutic effects. We describe the case of an elderly woman with multiple metastatic advanced ENEC treated with tislelizumab combined with anlotinib as second-line therapy, achieving complete remission in a short period and long-term survival. In total, 21 cycles of tislelizumab combined with anlotinib were given to this patient. After two cycles, the patient's neuron-specific enolase level decreased from 181.8 to 22.9 µg/L and remained at normal levels throughout treatment. Progression-free survival and overall survival were 16 and 21 months, respectively, in this patient. No obvious side effects were observed. Thus, tislelizumab and anlotinib could represent a novel therapeutic option for advanced ENEC.

Objective: To investigate the response characteristics of patients with locally advanced/metastatic non-squamous non-small cell lung cancer (nsq-NSCLC) treated with tislelizumab in combination with chemotherapy in the first line. Methods: Patients with nsq-NSCLC who achieved complete or partial remission after treatment with tislelizumab in combination with chemotherapy or chemotherapy alone in the RATIONALE 304 study, as assessed by an independent review board, were selected to analyze the response characteristics and safety profile of the responders. Time to response (TTR) was defined as the time from randomization to the achievement of first objective response. Depth of response (DpR) was defined as the maximum percentage of tumor shrinkage compared with the sum of the baseline target lesion length diameters. Results: As of January 23, 2020, 128 patients treated with tislelizumab in combination with chemotherapy achieved objective tumor response (responders), representing 57.4%(128/223) of the intention-to-treat population, with a TTR of 5.1 to 33.3 weeks and a median TTR of 7.9 weeks. Of the responders (128), 50.8%(65) achieved first remission at the first efficacy assessment (week 6), 31.3%(40) at the second efficacy assessment (week 12), and 18.0%(23) at the third and subsequent tumor assessments. The percentages of responders who achieved a depth of tumor response of 30% to <50%, 50% to <70% and 70% to 100% were 45.3%(58/128), 28.1%(36/128) and 26.6%(34/128), respectively, with median progression-free survival (PFS) of 9.0 months (95% CI: 7.7 to 9.9 months), 11.5 months (95% CI: 7.7 months to not reached) and not reached (95% CI: 11.8 months to not estimable), respectively. Tislelizumab plus chemotherapy were generally well tolerated in responders with similar safety profile to the overall safety population. Conclusion: Among responders to tislelizumab in combination with chemotherapy for nsq-NSCLC, 82.0%(105/128) achieves response within the first two tumor assessments (12 weeks) and 18.0%(23/128) achieves response at later (18 to 33 weeks) assessments, and there is a trend toward prolonged PFS in responders with deeper tumor response.

Introduction: CTLA-4/PD-1/PD-L1- directed immune checkpoint inhibitors (ICIs) are one of the standard therapies for the treatment of advanced non-small cell lung cancer (NSCLC). However, some new classes of monoclonal antibodies are emerging as promising therapies for advanced NSCLC., Areas Covered: Therefore, this paper aims to provide a comprehensive review of the recently approved as well as emerging monoclonal antibody immune checkpoint inhibitors for the treatment of advanced NSCLC., Expert Opinion: Further and larger studies will be needed to explore the promising emerging data on new ICIs. Future phase III trials could allow us to properly assess the role of each immune checkpoints in the wider context of the tumor microenvironment and thus the best new ICIs to use, the best approach and the most effective subset of patients to select.

Immunotherapy plus chemotherapy has been approved for the first-line treatment of extensive-stage small cell lung cancer (ES-SCLC, stage IV). Recently, the 2023 version of the National Comprehensive Cancer Network Guidelines recommended immunotherapy plus chemotherapy as the neoadjuvant regimen in patients with resectable non-small cell lung cancer (NSCLC). However, it is still unclear whether the combination regimen of immunotherapy plus chemotherapy is also beneficial for SCLC in the neoadjuvant context. Here, we report the case of a patient with stage IIIB SCLC who showed long-term survival and good tolerance to the neoadjuvant chemoimmunotherapy consisting of tislelizumab (an anti-PD-1 monoclonal antibody) plus etoposide-carboplatin. The patient achieved pathological complete response after receiving two cycles of neoadjuvant tislelizumab and chemotherapy followed by surgery. Two courses of post-operative tislelizumab and etoposide-carboplatin treatment were performed. The patient has survived for more than 23 months with no recurrence or metastases after neoadjuvant therapy. Multiplexed immunofluorescence and immunohistochemistry staining showed that the post-treatment specimens had remarkable immune cells infiltration, including CD3+ T cells, CD4+ T cells, and CD8+ T cells, which contrasted with very low levels of these cells in the pre-treatment samples. This study is, to the best of our knowledge, the first attempt to present the neoadjuvant chemoimmunotherapy of tislelizumab in combination with etoposide-carboplatin in SCLC. Our study suggested that neoadjuvant tislelizumab plus chemotherapy may facilitate radical resection and benefit patients with locally advanced (stage IIB-IIIC) SCLC., 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 © 2023 Zhou, Chen, Huang, Jiang, Liao, Gou, Lu, Che and Zhang.)

Background and Objective: Tislelizumab is a programmed cell death protein-1 (PD-1) inhibitor. Tislelizumab plus chemotherapy as first-line option for advanced non-squamous non-small cell lung cancer (NSCLC), compared with chemotherapy alone, resulted in significantly prolonged survival outcomes; however, evidence regarding its relative efficacy and cost is lacking. We aimed to evaluate the cost-effectiveness of tislelizumab plus chemotherapy compared with that of chemotherapy alone, from the health care perspective in China., Methods: A partitioned survival model (PSM) was used for this study. The survival data were obtained from the RATIONALE 304 trial. Cost-effectiveness was defined as incremental cost-effectiveness ratio (ICER) less than the willingness to pay (WTP) threshold. Incremental net health benefits (INHB), incremental net monetary benefits (INMB), and subgroup analyses were also assessed. Sensitivity analyses were further established to assess the model stability., Results: Compared with chemotherapy alone, tislelizumab plus chemotherapy increased by 0.64 quality-adjusted life-years (QALYs) and 1.48 life-years, and yielded an increase of $16,631 in cost per patient. The INMB and INHB were $7,510 and 0.20 QALYs at a WTP threshold of $38,017/QALY, respectively. The ICER was $26,162/QALY. The outcomes were most sensitive to the HR of OS for tislelizumab plus chemotherapy arm. The probability of tislelizumab plus chemotherapy being considered cost-effective was 87.66% and >50% in most of the subgroups at the WTP threshold of $38,017/QALY. At the WTP threshold of $86,376/QALY, the probability achieved 99.81%. Furthermore, the probability of tislelizumab plus chemotherapy being considered cost-effective in subgroups of patients with liver metastases and PD-L1 expression ≥50% were 90.61 and 94.35%, respectively., Conclusion: Tislelizumab plus chemotherapy is likely to be cost-effective as a first-line treatment for advanced non-squamous NSCLC in China., 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 © 2023 Liang, Chen, Li and Li.)

Introduction: The phase 3 RATIONALE-303 trial (NCT03358875) investigated the efficacy and safety of tislelizumab versus docetaxel in pretreated patients with advanced NSCLC. Here, we report the efficacy and safety results and describe the exploratory biomarker analyses., Methods: A total of 805 patients aged more than or equal to 18 years with locally advanced or metastatic squamous or nonsquamous NSCLC were randomized 2:1 to intravenous tislelizumab 200 mg or docetaxel 75 mg/m 2 every 3 weeks. Co-primary end points were overall survival (OS) in the intent-to-treat (ITT) and programmed death-ligand 1 (PD-L1) tumor cell expression greater than or equal to 25% populations. The exploratory biomarker analyses included PD-L1 expression, tumor mutation burden, and gene expression profile., Results: At the prespecified interim analysis (August 10, 2020), the co-primary end point of OS in the ITT population was met, with a statistically significant and clinically meaningful improvement in OS with tislelizumab versus docetaxel (median 17.2 versus 11.9 mo, respectively; hazard ratio [HR] = 0.64, p < 0.0001). At the final analysis (July 15, 2021), the other co-primary end point of OS in the PD-L1 tumor cell greater than or equal to 25% population was further met (median 19.3 versus 11.5 mo, respectively; HR = 0.53, p < 0.0001), and OS continued to improve in the ITT population (median 16.9 versus 11.9 mo, respectively, HR = 0.66). Exploratory biomarker analyses revealed the potential association of NOTCH1-4 mutations with improved tislelizumab efficacy for both OS and progression-free survival, whereas tissue tumor mutation burden correlated with progression-free survival benefit, but not OS benefit. No new safety signals were identified., Conclusions: Tislelizumab was found to have a significantly improved and long-term clinical benefit in OS versus docetaxel in pretreated patients with advanced NSCLC, regardless of PD-L1 expression., (Copyright © 2022 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.)

Background: Pulmonary sarcomatoid carcinoma (PSC) is a rare and aggressive disease without standardized treatment strategies. The efficacy of second-line or beyond immune checkpoint inhibitors (ICIs) has been proven in recent studies, whereas the evidence for first-line immunotherapy for PSC is still limited to case reports and remains poorly understood., Materials and Methods: This was a multicenter, retrospective analysis of 21 patients with a histological diagnosis of PSC who received ICI as first-line therapy from January 2019 to March 2022. The expression of PD-L1 was evaluated by immunohistochemistry (IHC) using the monoclonal antibody 22C3. Low and high PD-L1 expressions were defined using the tumor proportion score (TPS), with cutoffs of 1 and 50%, respectively., Results: All eight patients had PD-L1 positivity who underwent PD-L1 expression assessment, and six patients (6/8, 75.0%) had high PD-L1 expression. Among the 21 PSC patients, seven received tislelizumab, six received camrelizumab, four received sintilimab, three received pembrolizumab, and one received durvalumab. Among them, 18 PSCs received combination therapy, whereas another three PSCs received immunotherapy alone. Out of the 21 PSC patients, 12 (57.1%) achieved a partial response (PR), and five patients had stable disease (SD) as the best response, whereas four PSCs experienced dramatic progressive disease (PD). The median progression-free survival (PFS) was 9.2 (95% CI [4.3, 14.1]) months, and the median OS was 22.8 (95% CI [4.0, 41.5]) months. Among the three treatment groups (immunotherapy alone, immunotherapy combined with anlotinib, and chemoimmunotherapy), the median PFS was 8.0, 9.4, and 9.6 months, and the median OS was 19.0, 22.8, and 30.6 months, respectively. There was no difference in PFS and OS between the three treatment regimen groups ( P = 0.86 and P = 0.34, respectively) and different immunotherapies ( P = 0.10 and P = 0.23, respectively). No serious adverse events (grade ≥ 3) were noted., Conclusion: First-line immunotherapy has promising therapeutic potential in the treatment of PSC. More studies are warranted to confirm these findings., 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 © 2022 Qian, Wang, Liu, Yuan, Fang, Zhang, Yuan, Chen, Yu, Wang, Yin and Li.)

Pulmonary sarcomatoid carcinoma (PSC), characterized by poor differentiation, aggressive progression, and early metastasis, is a rare type of non-small cell lung carcinoma (NSCLC), which shows a low response rate to conventional antitumor therapies and has a poor prognosis. With the achievements in gene sequencing, targeted therapy, and immunotherapy, several new approaches have recently been explored in PSC treatment. A small case series of PSC patients were found to have programmed death-ligand 1 (PD-L1) overexpression, a prerequisite for PD-1 inhibiting therapy, which made immunotherapy possible. However, anti-PD-1 treatment for PSCs was still at a preliminary stage. Here, we report the successful outcome of tislelizumab monotherapy in a patient with advanced PSC with pleural invasion, thus providing a novel promising approach for PSC patients with PD-L1 overexpression., (© 2021 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.)

Tislelizumab is an anti-programmed death receptor 1 (PD-1) monoclonal immunoglobulin G 4 antibody developed by BeiGene. The structure of tislelizumab has been modified to maximally inhibit the binding of PD-1 to programmed death ligand 1 (PD-L1) and minimize the binding of tislelizumab to Fcγ receptors. In clinical studies, tislelizumab has shown preliminary anti-tumor effects in various solid tumors, such as Hodgkin's lymphoma, urothelial carcinoma, lung cancer, gastric and esophageal cancer, liver cancer, nasopharyngeal carcinoma, colorectal cancer, and microsatellite instability-high/mismatch repair-deficient tumors. In addition, it also showed new promise in solid tumor treatment in combination with ociperlimab. Due to its satisfactory anti-tumor effects, tislelizumab has received approvals in China for the treatment of classical Hodgkin's lymphoma, urothelial carcinoma, squamous non-small cell lung cancer, non-squamous non-small cell lung cancer, and hepatocellular carcinoma, and it is now under investigation for a new indication in microsatellite instability-high/mismatch repair-deficient tumors. Moreover, it has been granted orphan designations in hepatocellular carcinoma, esophageal cancer, and gastric cancer, including cancer of the gastroesophageal junction, by the US Food and Drug Administration. Tislelizumab has an acceptable safety profile; the most common adverse effects include fatigue, anemia, and decreased neutrophil count, while the most fatal events have been related to respiratory infection or failure, and hepatic injury. Tislelizumab has an economic advantage compared with other well-studied PD-1/PD-L1 inhibitors; thus, the introduction of it could provide clinical oncologists with an effective weapon against tumors and may alleviate the burden of cancer patients.

Introduction: Tislelizumab, an anti-programmed cell death protein-1 antibody, was specifically engineered to minimize FcɣR macrophage binding to abrogate antibody-dependent phagocytosis. Compared with chemotherapy alone, tislelizumab plus chemotherapy may improve clinical outcomes in patients with advanced nonsquamous NSCLC (nsq-NSCLC)., Methods: In this open-label phase 3 trial (RATIONALE 304; NCT03663205), patients with histologically confirmed stage IIIB or IV nsq-NSCLC were randomized (2:1) to receive either arm A: tislelizumab plus platinum (carboplatin or cisplatin) and pemetrexed every 3 weeks (Q3Ws) or arm B: platinum and pemetrexed alone Q3W during induction treatment, followed by intravenous maintenance pemetrexed Q3W. The primary end point was progression-free survival (PFS) assessed by an independent review committee; clinical response and safety and tolerability were secondary end points., Results: Overall, 332 patients (n = 222 [A]; n = 110 [B]) received treatment. With a median study follow-up of 9.8 months, PFS was significantly longer with tislelizumab plus chemotherapy compared with chemotherapy alone (median PFS: 9.7 versus 7.6 mo; hazard ratio = 0.645 [95% confidence interval: 0.462-0.902], p = 0.0044). In addition, response rates were higher and response duration was longer with combination therapy versus chemotherapy alone. Hematologic adverse events (AEs) were common in both treatment arms; the most reported AEs were grades 1 to 2 in severity. The most common grade greater than or equal to 3 AEs were associated with chemotherapy and included neutropenia (44.6% [A]; 35.5% [B]) and leukopenia (21.6% [A]; 14.5% [B])., Conclusions: Addition of tislelizumab to chemotherapy resulted in significantly prolonged PFS, higher response rates, and longer response duration compared with chemotherapy alone, identifying a new potential option for first-line treatment of advanced nsq-NSCLC irrespective of disease stage., (Copyright © 2021 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.)

Introduction: Non-small cell lung cancer (NSCLC) accounts for most lung cancers worldwide and has a poor prognosis at later stages; programmed cell death protein-1 (PD-1) and programmed death-ligand 1 (PD-L1) inhibitors have provided promising new treatment approaches for these patients. Tislelizumab, an anti-PD-1 monoclonal antibody, was engineered to minimize binding to FcγR on macrophages to abrogate antibody-dependent phagocytosis, a mechanism of T-cell clearance and potential resistance to anti-PD-1 therapy. Tislelizumab has demonstrated clinical activity and is approved in China for treatment of previously treated classical Hodgkin lymphoma and previously treated metastatic PD-L1-high urothelial carcinoma., Areas Covered: This review summarizes the clinical efficacy, safety, and tolerability of tislelizumab in patients with NSCLC and examines the mechanism of action, pharmacokinetic, and pharmacodynamic profiles of tislelizumab., Expert Opinion: Tislelizumab has higher affinity to PD-1 than pembrolizumab and nivolumab, potentially due to its differential PD‑1 binding orientation. Tislelizumab demonstrated encouraging efficacy results, long duration of response, and a manageable safety profile across multiple clinical trials in advanced NSCLC. Ongoing trials of drug combinations (e.g. tislelizumab plus angiogenesis inhibitors, immune checkpoint inhibitors, or immune agonists) and examining efficacy across the severity of disease will provide opportunities to understand and feature tislelizumab in clinical practice.

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.)