Comparison of atezolizumab,durvalumab, pembrolizumab,and nivolumab as first-line treatment in patients with extensive-stage small cell lung cancer: A systematic review and network meta-analysis

Background:In recent years, immune checkpoint inhibitors (ICIs) including atezolizumab, durvalumab, pembrolizumab, and nivolumab have reported their efficacy and safety profile in patients with extensive-stage small cell lung cancer (ES-SCLC). However, given the diverse efficacy and inconsistent safety among the ICIs, with the absence of head-to-head researches designed to evaluate the efficacy among them, it might bring with confusion on selection in clinical practice.Objectives:The present systematic review and network meta-analysis was performed to conduct indirect comparisons on efficacy and safety profile among ICIs, including atezolizumab, durvalumab, pembrolizumab, and nivolumab as first-line treatment in patients with ES-SCLC.Design:Several databases were retrieved with established criteria until June 20, 2020, with the main MeSH Terms and their similarities. Hazard ratios of overall survival (OS) and progression-free survival (PFS), odds ratios (ORs) of disease control rate (DCR), objective response rate (ORR), and adverse events (AEs) were compared indirectly with network meta-analysis.Data sources:Medline, Cochrane library, and Embase.Eligibility criteria:Prospective, randomized, controlled clinical studies, which reported PFS, OS, and AEs.Data extraction and synthesis:Clinical characteristics were extracted by the 2 authors independently. Comparisons of HRs were calculated for PFS and OS by random effect model. ORR, DCR, and AEs were presented with ORs. Based on surface under the cumulative ranking curve, and forest plots, efficacy and safety of the treatments were ranked, with predicted histogram described.Results:In total, there were 4 studies including 1547 patients who met the eligibility criteria and enrolled. For indirect comparisons, no significant difference on PFS was observed between atezolizumab and durvalumab (HR 0.96, 95% CI, 0.72–1.29), or between atezolizumab and pembrolizumab (HR 1.05, 95% CI, 0.78–1.43), or between atezolizumab and nivolumab (HR 1.18, 95% CI, 0.79–1.79), or between durvalumab and pembrolizumab (HR 1.10, 95% CI, 0.84–1.43). or between durvalumab and nivolumab (HR 1.23, 95% CI, 0.83–1.82), or between pembrolizumab and nivolumab (HR 1.12, 95% CI, 0.76–1.66), nor significant difference on OS observed between atezolizumab and durvalumab (HR 0.93, 95% CI, 0.67–1.30), or between atezolizumab and pembrolizumab (HR 0.88, 95% CI, 0.62–1.24), or between atezolizumab and nivolumab (HR 1.04, 95% CI, 0.66–1.66), or between durvalumab and pembrolizumab (HR 0.94, 95% CI, 0.70–1.25), or between durvalumab and nivolumab (HR 1.12, 95% CI, 0.73–1.71), or between pembrolizumab and nivolumab (HR 1.19, 95% CI, 0.77–1.84). However, durvalumab was shown statistical superiority on ORR when compared with atezolizumab (HR 0.79, 95% CI, 0.64–0.98), also with significantly higher risk on immune-related AEs when compared with atezolizumab (OR 0.22, 95% CI, 0.10–0.50), and pembrolizumab (OR 3.12, 95% CI, 1.27–7.64).Conclusions:Results of the study revealed that there was no statistical difference on PFS or OS among agents of atezolizumab, durvalumab, pembrolizumab, and nivolumab as first-line treatment in patients with ES-SCLC. However, durvalumab was shown superiority on ORR when compared with atezolizumab, also with significantly higher risk on immune-related AEs.     

Navigating the new landscape of second‐line treatment in advanced hepatocellular carcinoma

Sorafenib and lenvatinib are approved for first‐line treatment of patients with advanced hepatocellular carcinoma (HCC), and the efficacy of atezolizumab plus bevacizumab has been demonstrated versus sorafenib. Over time, first‐line treatment frequently fails, and regorafenib, cabozantinib, ramucirumab (for patients with alpha fetoprotein ≥400 ng/mL), nivolumab, pembrolizumab and ipilimumab plus nivolumab are approved for use after sorafenib (but not lenvatinib) treatment in advanced HCC. Given the considerable complexity in the therapeutic landscape, the objective of this review was to summarize the clinical evidence for second‐line agents and provide practical guidance for selecting the best sequential treatment approach. The timing and sequencing of treatment switches are key to optimizing patient outcomes in advanced HCC, and decisions should be informed by reasons for discontinuation of previous therapy and disease progression. It is important not to switch too soon, because sequential treatment benefit may then be lost, nor should switching be delayed too long. Effectiveness, safety and tolerability, patient quality of life, route of administration, dosing regimen, drug class, molecular target and individual patients’ characteristics, including comorbidities, inform the selection of second‐line systemic treatment, independently of the aetiology of HCC, tumour stage and the response to previous treatment. Biomarkers predictive of treatment effectiveness are of great value, but currently biomarker‐driven patient selection is possible only in the case of ramucirumab. The approval of new combination therapies for advanced HCC in the first‐line setting will further increase the complexity of decision‐making. However, the important factors will remain the individual patient’s characteristics and preferences.     

Effect of pembrolizumab on T lymphocyte subsets in patients with advanced oral cancer and its therapeutic effect

Background:The aim of this study is to investigate changes of peripheral blood lymphocyte subsets before and after treatment with pembrolizumab for advanced oral cancer and its clinical sig-nificance.Methods:32 patients with advanced oral cancer who received pembrolizumab treatment were selected as observation group, 30 healthy people during the same period were selected as control group. Before treatment and in cycles 1, 2, 3 and 4 after treatment, fluid cytometry was used to detect changes in levels of lymphocyte subsets in peripheral blood of patients.Results:CD3⁺, CD4⁺, CD4⁺/CD8⁺indexes of patients with advanced oral cancer before treatment were significantly lower than those in control group (P < .05), CD8⁺level was significantly increased (P < .05); After 1 cycle of pembrolizumab treatment, there was no significant difference in changes of lymphocyte subsets compared with before immunotherapy; After 2 and 3 cycles of treatment, CD3⁺, CD4⁺, CD4⁺/CD8⁺values were higher than before the treatment (P > .05), CD8⁺index was slightly lower than before treatment (P < .05); After fourth cycle of treatment, CD3⁺, CD4⁺, CD4⁺/CD8⁺values were significantly improved compared to before treatment (P < .05), CD8⁺index was significantly lower than before treatment (P < .05); In treatment process of patients with stable disease (SD)/partial response (PR), the CD3⁺, CD4⁺, CD4⁺/CD8⁺values of fourth cycles were higher than before treatment (P < .05), CD8⁺index was lower than before treatment (P < .05); During treatment of progressive disease (PD) patients, changes of lymphocyte subsets in fourth cycles were not significantly different from those before treatment (P > .05). This article shows through analysis that expression of programmed cell death ligand 1 (PD-L1) and pathological types have no obvious influence on effect of immunotherapy. Multi-factor analysis shows that it is more meaningful to observe the changes of CD3⁺, CD4⁺and CD8⁺at the same time to predict effect of immunotherapy.Conclusion:Pembrolizumab can regulate changes of T lymphocyte subsets in patients with advanced oral cancer, improve immune status of patients, there is no obvious adverse reaction. Monitoring changes of lymphocyte subsets during treatment can predict effect of immunotherapy.     

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特异性免疫治疗主要包括皮下免疫治疗(SCIT)和舌下免疫治疗(SLIT),经全世界各国医生临床研究表明是安全的。它的不良反应主要是过敏反应,常见为局部表现,但严重全身性不良反应可以威胁患者生命甚至死亡。不良反应常见于剂量递增阶段,SCIT注射后短时间内出现手心和脚底烧灼感、痒感和热感,全身荨麻疹是严重全身不良反应的前驱症状,应立即肌注或静注抗阻胺药,出现低血压症状立即肌注肾上腺素;在治疗前与患者做好沟通,遵守其说明书的要求,注意其危险因素,同时在治疗早期联合药物治疗控制患者过敏性疾病的症状,可以有效减少免疫治疗的不良反应。     

Safe and effective IV regional anesthesia for use in the emergency department

The mini-dose Bier block, a technique of intravenous (IV) regional anesthesia that uses low-dose lidocaine and provides safe and effective anesthesia for outpatient closed reductions of upper extremity fractures and dislocations, is presented. This procedure was evaluated in two hospital emergency departments in 105 patients (ages 2 to 86). Ninety-five percent achieved adequate anesthesia (minimal or no pain on closed reduction). No significant complications were noted. Full neurologic function returned in ten minutes in all cases. Both patient and physician satisfaction with the procedure were high. The mini-dose Bier block creates the potential for significant cost savings in cases previously treated in the operating room by providing a safe, effective technique of IV regional anesthesia for outpatient use.     

Safe and effective IV regional anesthesia for use in the emergency department

The mini-dose Bier block, a technique of intravenous (IV) regional anesthesia that uses low-dose lidocaine and provides safe and effective anesthesia for outpatient closed reductions of upper extremity fractures and dislocations, is presented. This procedure was evaluated in two hospital emergency departments in 105 patients (ages 2 to 86). Ninety-five percent achieved adequate anesthesia (minimal or no pain on closed reduction). No significant complications were noted. Full neurologic function returned in ten minutes in all cases. Both patient and physician satisfaction with the procedure were high. The mini-dose Bier block creates the potential for significant cost savings in cases previously treated in the operating room by providing a safe, effective technique of IV regional anesthesia for outpatient use.     

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特异性免疫治疗(SIT)是变态反应疾病特有的病因治疗方法,是除避免接触变应原外能够影响变态反应疾病自然进程的惟一治疗手段。针对目前SIT特别是皮下注射免疫治疗(SCIT)存在的问题,国内外变态反应学者进行了大量研究,文章对SIT新的给药途径、新的适应证、变应原提取液制剂的改进、合并应用Anti-IgE治疗及cDNA免疫治疗等方面的研究进展进行了简要综述并对其临床应用前景进行了展望。     

Nationwide questionnaire-based survey of oral immunotherapy in Japan

Background

Clinical trials on oral immunotherapy (OIT) have been increasing for nearly a decade; however, several national guidelines do not recommend OIT as a standardized procedure. The aim of this study was to obtain insights into the current use and practice of OIT in Japan.

变应性疾病特异性免疫治疗机制研究进展

特异性免疫治疗是特异性Ⅰ型变态反应性疾病的惟一有效的可以改变其自然病程的方法.虽然其机制不十分清楚,但已有很大进展.随着变应原疫苗的标准化及治疗方案的改进,使其疗效和安全性不断提高.本文综述了近几年来对特异性免疫治疗机制方面的研究进展.     

吸烟与支气管哮喘研究进展

吸烟是支气管哮喘(简称哮喘)发病的危险因素之一。吸烟的哮喘患者在临床表型、影像学表现和气道炎症方面与普通哮喘患者不同。吸烟可加速肺功能下降,加重哮喘病情。吸烟哮喘患者气道重塑更严重。吸烟降低哮喘患者激素治疗敏感性。     

肝细胞癌免疫治疗的现状与挑战

免疫疗法是目前肿瘤治疗的一种新方法,应用前景广阔,在治疗相关毒性和疗效方面较传统疗法均具有明显优势。免疫检查点抑制、克服肿瘤免疫逃逸和重建抗肿瘤免疫机制是肿瘤免疫治疗的关键。在肝细胞癌中,免疫治疗尚处于初级阶段,免疫治疗单独或联合其他治疗方法可能有利于控制肿瘤进展,但总体疗效仍然有限。本文结合免疫治疗在肿瘤中的研究和应用进展,分析了肝细胞癌免疫治疗研究现状以及面临的挑战。     

支气管哮喘和变应性鼻炎的舌下特异性免疫疗法进展

舌下特异性免疫疗法在支气管哮喘和变应性鼻炎的治疗方面发挥了重要作用,它提供了一种可以替代传统皮下免疫疗法的变应原免疫治疗方法.目前已经有两种制剂(滴剂和片剂)可以用于舌下特异性免疫疗法.研究表明舌下特异性免疫疗法是安全、有效的.     

Role of sublingual immunotherapy in the treatment of asthma: An updated systematic review

Background

The purpose of the systematic review is to evaluate the efficacy and safety of sublingual immunotherapy (SLIT) for the treatment of allergic asthma.

Methods

PubMed, Embase, and CENTRAL databases were searched, updating an earlier review (January 1, 2005 through May 8, 2017). Randomized, controlled studies (RCTs) were included, which reported one of the prespecified outcomes: asthma symptoms measured by control composite scores; quality of life; medication use; pulmonary physiology; and health‐care utilization. For safety outcomes, RCTs and observational studies were included. Two independent reviewers extracted data, assessed risk of bias, and graded strength of evidence (SOE) for each outcome.

Results

Fourteen RCTs (n = 2585) assessed the efficacy of SLIT for asthma. The RCTs utilized house dust mite (HDM), birch, or grass allergen. SLIT improved asthma symptoms (high SOE), decreased use of long‐term control medication, and improved forced expiratory volume in 1 second (FEV₁) (moderate SOE). SLIT may decrease quick‐relief medication use, and improve disease‐specific quality of life (low SOE). For safety, 20 RCTs and 10 observational studies (n = 3621) were identified. Local (risk differences ranged from ?0.03 to +0.765) and systemic allergic reactions (risk differences ranged from ?0.03 to +0.06) were a common occurrence in SLIT and control groups. Life‐threatening reactions were uncommon, with 3 cases of anaphylaxis and no deaths reported.

Conclusion

There is moderate‐to‐high strength evidence that SLIT improves allergic asthma symptoms, reduces long‐term control medication use, and improves FEV₁ based on studies of HDM, birch, and grass. SLIT rarely is associated with life‐threatening adverse events.