ORR, objective response rate

  • 文章类型: Editorial
    UNASSIGNED:先前报道的结果显示新辅助免疫疗法对可切除的非小细胞肺癌(NSCLC)具有良好的疗效。然而,目前尚无比较新辅助免疫治疗和化疗的随机对照试验报道.本研究的目的是评估新辅助免疫治疗与标准新辅助化疗相比,在可切除的非小细胞肺癌的短期临床结局和手术结局方面的优越性。
    未经授权:我们搜索了PubMed,Embase,Cochrane中央受控试验登记册,ClinicalTrials.gov数据库,WebofScience,以及截至2020年3月1日的多个主要癌症会议的摘要。短期临床结果(包括客观缓解率[ORR],主要病理反应,和病理完全缓解[pCR])和手术结果(包括手术切除率和R0切除率)。数据汇总为每个评估指标的估计合并值。使用标准方法评估纳入研究的偏倚风险。
    UNASSIGNED:本系统综述和荟萃分析了21项关于NSCLC新辅助免疫治疗和新辅助化疗的试验,包括1795名患者。仅接受程序性死亡配体1(PD-1/PD-L1)抑制剂(NeoIO)的患者(13.3%;95%置信区间[CI],9.0%-19.3%)与接受NeoIO联合化疗(CT)(62.5%;95%CI,54.4%-70.0%)或单独使用CT(41.6%;95%CI,36.8%-46.7%)(NeoIO与CT,P<.001;NeoIO+CT与CT,P<.001)。与单独接受NeoIO(10.6%;95%CI,6.5%-16.9%;P<.001)或标准CT(7.5%;95%CI,5.7%-9.8%;P<.001)相比,接受NeoIO+CT(36.2%;95%CI,19.2%-57.6%)与pCR率升高相关。新辅助CT(87.2%;95%CI,74.9%-94.0%)与单独NeoIO(92.7%;95%CI,83.4%-97.0%;P=.360)或NeoIO+CT(91.6%;95%CI,84.3%-95.7%;P=.409)相比,R0切除率较低。Meta回归显示,III期患者的比例较高与手术切除率和R0切除率降低相关,而新辅助免疫疗法未观察到影响.
    UNASSIGNED:目前的数据表明,与新辅助化疗相比,以免疫治疗为基础的方案可以提供优异的病理反应以及更高的完全切除率.新辅助化疗中免疫联合化疗可能是更有利的临床选择。需要进一步的随机对照试验来提供局部NSCLC新辅助免疫治疗的长期结果,并有助于指导临床实践。
    UNASSIGNED: Previously reported results have shown promising efficacy of neoadjuvant immunotherapy for resectable non-small cell lung cancer (NSCLC). However, no randomized control trials comparing neoadjuvant immunotherapy with chemotherapy have yet been reported. The aim of the present study was to evaluate the superiority of neoadjuvant immunotherapy compared with standard neoadjuvant chemotherapy in resectable NSCLC in terms of short-term clinical outcomes and surgical outcomes.
    UNASSIGNED: We searched PubMed, Embase, the Cochrane Central Register of Controlled Trials, the ClinicalTrials.gov database, Web of Science, and abstracts derived from multiple major cancer meetings up to March 1, 2020. Short-term clinical outcomes (including objective response rate [ORR], major pathologic response, and pathologic complete response [pCR]) and surgical outcomes (including surgical resection rate and R0 resection rate) were reported. Data were summarized as the estimated pooled value of each evaluated index. The risk of bias of included studies was assessed using standard methods.
    UNASSIGNED: This systematic review and meta-analysis of 21 trials on neoadjuvant immunotherapy and neoadjuvant chemotherapy for NSCLC included 1795 patients. Patients who received Programmed death ligand 1 (PD-1/PD-L1) inhibitors (NeoIO) alone (13.3%; 95% confidence interval [CI], 9.0%-19.3%) had the lowest ORR compared with those who received NeoIO plus chemotherapy (CT) (62.5%; 95% CI, 54.4%-70.0%) or CT alone (41.6%; 95% CI, 36.8%-46.7%) (NeoIO vs CT, P < .001; NeoIO + CT vs CT, P < .001). Receipt of NeoIO + CT (36.2%; 95% CI, 19.2%-57.6%) was associated with an elevated pCR rate compared with receipt of NeoIO alone (10.6%; 95% CI, 6.5%-16.9%; P < .001) or standard CT (7.5%; 95% CI, 5.7%-9.8%; P < .001). Neoadjuvant CT (87.2%; 95% CI, 74.9%-94.0%) was associated with a lower R0 resection rate compared with NeoIO alone (92.7%; 95% CI, 83.4%-97.0%; P = .360) or NeoIO + CT (91.6%; 95% CI, 84.3%-95.7%; P = .409). Meta-regression showed that a higher proportion of stage III patients was correlated with decreased surgical resection and R0 resection rates, whereas no impact was observed with neoadjuvant immunotherapy.
    UNASSIGNED: Current data suggest that compared with neoadjuvant chemotherapy, immunotherapy-based regimens may provide superior pathological response along with a higher rate of complete resection. Immunotherapy combined with chemotherapy in neoadjuvant chemotherapy may be a more favorable clinical option. Further randomized controlled trials are warranted to provide long-term results of neoadjuvant immunotherapy for localized NSCLC and help guide clinical practice.
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  • 文章类型: Journal Article
    患有非小细胞肺癌(NSCLC)的患者的死亡率相当高。这种类型的癌症主要是由于间变性淋巴瘤激酶(ALK)基因的重排而发生的,该重排导致形成融合基因NPM-ALK的癌基因。Brigatinib最近于2017年4月被FDA批准为用于NSCLC治疗的有效酪氨酸激酶抑制剂(TKI)。在目前的情况下,它不亚于一种神奇的药物,因为它适用于治疗晚期转移性ALK阳性NSCLC,一种致命的疾病,以克服各种其他ALK抑制剂如克唑替尼的耐药性,ceritinib和alectinib。除了ALK,它还对多种类型的激酶如ROS1,胰岛素样生长因子-1受体和EGFR具有活性。它可以通过分别使用N-[2-甲氧基-4-[4-(二甲基氨基)哌啶-1-基]苯胺]胍和2,4,5-三氯嘧啶以两种不同的方式合成。其结构主要由负责其药理活性的二甲基氧化膦基团组成。它对各种细胞系如HCC78、H2228、H23、H358、H838、U937、HepG2和Karpas-299具有活性。ALTA(AP26113肺癌试验中的ALK)1/2期试验的结果表明,90mg布格替尼7天,然后180mg第二天有效治疗NSCLC。布吉替尼已被证明具有有利的风险益处,并且是比可用的细胞毒性化学治疗剂更安全的药物。与其他FDA批准的相同条件的药物相比,它引起的轻微不良反应较少,可以通过改变剂量或提供良好的支持治疗来轻松管理。本文旨在为读者提供化学概述,药代动力学,布格替尼的药效学和安全性,解决了未满足的医疗需求。
    The mortality rate in patients suffering from non-small cell lung cancer (NSCLC) is quite high. This type of cancer mainly occurs due to rearrangements in the anaplastic lymphoma kinase (ALK) gene which leads to form an oncogene of fused gene NPM-ALK. Brigatinib is recently approved by FDA in April 2017 as a potent tyrosine kinase inhibitor (TKI) for the NSCLC therapy. In the present scenario, it is no less than a wonder drug because it is indicated for the treatment of advanced stages of metastatic ALK positive NSCLC, a fatal disease to overcome the resistance of various other ALK inhibitors such as crizotinib, ceritinib and alectinib. In addition to ALK, it is also active against multiple types of kinases such as ROS1, Insulin like growth factor-1Receptor and EGFR. It can be synthesized by using N-[2-methoxy-4-[4-(dimethylamino) piperidin-1-yl] aniline] guanidine and 2,4,5-trichloropyrimidine respectively in two different ways. Its structure consists of mainly dimethylphosphine oxide group which is responsible for its pharmacological activity. It is active against various cell lines such as HCC78, H2228, H23, H358, H838, U937, HepG2 and Karpas- 299. Results of ALTA (ALK in Lung Cancer Trial of AP26113) phase ½ trial shows that 90 mg of brigatinib for 7 days and then 180 mg for next days is effective in the treatment of NSCLC. Brigatinib has been shown to have favorable risk benefit profile and is a safer drug than the available cytotoxic chemotherapeutic agents. In comparison to other FDA approved drugs for the same condition, it causes fewer minor adverse reactions which can be easily managed either by changing the dose or by providing good supportive care. This article is intended to provide readers with an overview of chemistry, pharmacokinetic, pharmacodynamic and safety profile of brigatinib, which addresses an unmet medical need.
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