Crizotinib

克唑替尼
  • 文章类型: English Abstract
    Anaplastic lymphoma kinase (ALK) fusion gene is one of the most common driver gene in non-small cell lung cancer (NSCLC). Epidemiological data showed that ALK gene fusion is detected in 9.06% of Chinese advanced NSCLC patients. ALK-tyrosine kinase inhibitors (TKIs) have become the standard treatment for advanced NSCLC patients with ALK gene fusion. Seven different ALK-TKIs have been approved by the National Medical Products Administration (NMPA) of China, including crizotinib, ceritinib, alectinib, ensartinib, brigatinib, lorlatinib, and iruplinalkib. Iruplinalkib is a novel new-generation ALK-TKI independently developed in China. On June 27, 2023, the NMPA approved iruplinalkib for the treatment of locally advanced or metastatic ALK-positive NSCLC patients whose disease has progressed after previous treatment with crizotinib or who are intolerant to crizotinib. On January 16, 2024, the NMPA approved iruplinalkib for the first-line treatment of locally advanced or metastatic ALK-positive NSCLC patients. In order to better understand the efficacy and safety of iruplinalkib, and facilitate more rationally clinical application of iruplinalkib, the Medical Oncology Branch of China International Exchange and Promotive Association for Medical and Health Care and the Chinese Association for Clinical Oncologists co-organized experts to compile the \"Chinese expert consensus on iruplinalkib for the treatment of locally advanced or metastatic ALK-positive non-small cell lung cancer (2024 edition)\".
    间变性淋巴瘤激酶(ALK)融合基因是非小细胞肺癌(NSCLC)常见的驱动基因之一。流行病学数据显示,在中国晚期NSCLC患者中ALK融合基因的阳性率为9.06%。ALK酪氨酸激酶抑制剂(TKIs)已经成为ALK融合基因阳性晚期NSCLC患者的标准治疗选择。目前中国国家药品监督管理局已经批准7种ALK-TKIs上市,分别是克唑替尼、塞瑞替尼、阿来替尼、恩沙替尼、布格替尼、洛拉替尼和伊鲁阿克。伊鲁阿克是中国自主研发的新型ALK-TKI,2023年6月27日,国家药品监督管理局批准伊鲁阿克上市,用于既往接受过克唑替尼治疗后疾病进展或对克唑替尼不耐受的ALK融合基因阳性局部晚期或转移性NSCLC患者的治疗,2024年1月16日,国家药品监督管理局批准伊鲁阿克用于ALK融合基因阳性局部晚期或转移性NSCLC患者的一线治疗。为了帮助广大医师更好地了解伊鲁阿克的疗效和安全性,使伊鲁阿克得到更合理的临床应用,中国医疗保健国际交流促进会肿瘤内科学分会和中国医师协会肿瘤医师分会组织专家编写了《伊鲁阿克治疗间变性淋巴瘤激酶融合基因阳性局部晚期或转移性非小细胞肺癌中国专家共识(2024版)》。.
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  • 文章类型: Journal Article
    提供基于证据的建议,更新2021ASCO和安大略省健康(安大略省癌症护理)指南,以治疗具有驱动改变的IV期非小细胞肺癌(NSCLC)患者的全身治疗。
    ASCO根据对2020年至2021年随机对照试验的持续系统评价更新了建议。
    本指南更新反映了自上次更新以来证据的变化。两项研究提供了证据基础。感兴趣的结果包括疗效和安全性。
    对于有间变性淋巴瘤激酶重排的患者,性能状态(PS)为0-2,以前未治疗的非小细胞肺癌,临床医生应提供阿来替尼或布格替尼或洛拉替尼.对于有间变性淋巴瘤激酶重排的患者,PS为0-2,以前未经治疗的非小细胞肺癌,如果阿列替尼,布加替尼,或洛拉替尼不可用,临床医生应提供色瑞替尼或克唑替尼.对于RET重排的患者,PS为0-2,以前未经治疗的非小细胞肺癌,临床医生可提供selpercatinib或pralsetinib.在第二行,对于没有接受RET靶向治疗的RET重排患者,临床医生可提供selpercatinib或pralsetinib.其他信息可在www上获得。asco.org/胸癌指南。
    To provide evidence-based recommendations updating the 2021 ASCO and Ontario Health (Cancer Care Ontario) guideline on systemic therapy for patients with stage IV non-small-cell lung cancer (NSCLC) with driver alterations.
    ASCO updated recommendations on the basis of an ongoing systematic review of randomized control trials from 2020 to 2021.
    This guideline update reflects changes in evidence since the previous update. Two studies provide the evidence base. Outcomes of interest include efficacy and safety.
    For patients with an anaplastic lymphoma kinase rearrangement, a performance status (PS) of 0-2, and previously untreated NSCLC, clinicians should offer alectinib or brigatinib or lorlatinib. For patients with an anaplastic lymphoma kinase rearrangement, a PS of 0-2, and previously untreated NSCLC, if alectinib, brigatinib, or lorlatinib are not available, clinicians should offer ceritinib or crizotinib. For patients with a RET rearrangement, a PS of 0-2, and previously untreated NSCLC, clinicians may offer selpercatinib or pralsetinib. In second line, for patients with a RET rearrangement who have not received RET-targeted therapy, clinicians may offer selpercatinib or pralsetinib.Additional information is available at www.asco.org/thoracic-cancer-guidelines.
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  • 文章类型: Editorial
    肺癌是全球最常见的恶性肿瘤,也是癌症死亡的主要原因。晚期非小细胞肺癌(NSCLC)的诊断与3.2%的5年相对生存率相关。ROS原癌基因1(ROS1)是NSCLC的致癌驱动因素,发生在多达2%的病例中,通常与年龄较小和从不吸烟或吸烟的历史有关。酪氨酸激酶抑制剂(TKI)克唑替尼抑制具有ROS1重排的肿瘤的早期试验结果显示,客观缓解率(ORR)为72%(95%CI58-83%),中位无进展生存期(PFS)为19.3个月(95%CI15.2~39.1个月),中位总生存期(OS)为51.4个月(95%CI29.3个月未达到).因此,随着高效ROS1靶向TKI治疗的可用性,建议对所有NSCLC患者进行前期的ROS1状态分子检测以及EGFR和ALK检测.我们回顾了通过免疫组织化学(IHC)和荧光原位杂交(FISH)进行ROS1测试的组织要求,并提出了一种用于晚期NSCLC的测试算法,并考虑了ROS1病理学测试的未来可能会如何发展。
    Lung cancer is the most commonly diagnosed malignancy and the leading cause of death from cancer globally. Diagnosis of advanced non-small cell lung cancer (NSCLC) is associated with 5-year relative survival of 3.2%. ROS proto-oncogene 1 (ROS1) is an oncogenic driver of NSCLC occurring in up to 2% of cases and commonly associated with younger age and a history of never or light smoking. Results of an early trial with the tyrosine kinase inhibitor (TKI) crizotinib that inhibits tumours that harbour ROS1 rearrangements have shown an objective response rate (ORR) of 72% (95% CI 58-83%), median progression free survival (PFS) of 19.3 months (95% CI 15.2-39.1 months) and median overall survival (OS) of 51.4 months (95% CI 29.3 months to not reached). Therefore, with the availability of highly effective ROS1-targeted TKI therapy, upfront molecular testing for ROS1 status alongside EGFR and ALK testing is recommended for all patients with NSCLC. We review the tissue requirements for ROS1 testing by immunohistochemistry (IHC) and fluorescent in situ hybridisation (FISH) and we present a testing algorithm for advanced NSCLC and consider how the future of pathology testing for ROS1 may evolve.
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  • DOI:
    文章类型: Journal Article
    BACKGROUND: The SCAN lung cancer workgroup aimed to develop Singapore Cancer Network (SCAN) clinical practice guidelines for the use of systemic therapy in advanced non-small cell lung cancer (NSCLC) in Singapore.
    METHODS: The workgroup utilised a modified ADAPTE process to calibrate high quality international evidence-based clinical practice guidelines to our local setting.
    RESULTS: Five international guidelines were evaluated- those developed by the National Comprehensive Cancer Network (2014), the European Society of Medical Oncology (2014), the National Institute of Clinical Excellence (2012), the Scottish Intercollegiate Guidelines Network (2014) and Cancer Care Council Australia (2012). Recommendations on systemic treatment for advanced NSCLC were produced.
    CONCLUSIONS: These adapted guidelines form the SCAN guidelines 2015 for systemic therapy of advanced or metastatic NSCLC.
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  • 文章类型: News
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  • 文章类型: Journal Article
    在非小细胞肺癌(NSCLC)中发现间变性淋巴瘤激酶(ALK)重排的4年内,ALK抑制剂克唑替尼获得美国和欧洲批准用于治疗晚期ALK阳性NSCLC.这是由于克唑替尼在ALK阳性NSCLC患者的I期和II期试验中观察到的惊人反应数据,以及观察到的良好耐受性和安全性。最近发表的III期数据确立了克唑替尼作为该NSCLC分子亚群的新治疗标准。如此迅速批准的结果,然而,是有限的临床经验和有关最佳治疗管理的信息相对匮乏。在这次审查中,我们讨论了克唑替尼的发展及其安全性的临床相关性,详细检查克唑替尼相关不良事件,并提出具体的管理建议.在临床研究中,克唑替尼相关不良事件的严重程度大多为轻度至中度,在大多数情况下,适当的监测和支持疗法被认为可有效避免中断或减少剂量。还讨论了疾病进展后患者使用克唑替尼后的治疗管理。根据现有的临床数据,很明显,在实体瘤定义的疾病进展的反应评估标准后,患者可能从克唑替尼获得延长的益处,只要患者获益,克唑替尼应继续治疗。
    Within 4 years of the discovery of anaplastic lymphoma kinase (ALK) rearrangements in non-small cell lung cancer (NSCLC), the ALK inhibitor crizotinib gained US and European approval for the treatment of advanced ALK-positive NSCLC. This was due to the striking response data observed with crizotinib in phase I and II trials in patients with ALK-positive NSCLC, as well as the favorable tolerability and safety profile observed. Recently published phase III data established crizotinib as a new standard of care for this NSCLC molecular subset. A consequence of such rapid approval, however, is the limited clinical experience and relative paucity of information concerning optimal therapy management. In this review, we discuss the development of crizotinib and the clinical relevance of its safety profile, examining crizotinib-associated adverse events in detail and making specific management recommendations. Crizotinib-associated adverse events were mostly mild to moderate in severity in clinical studies, and appropriate monitoring and supportive therapies are considered effective in avoiding the need for dose interruption or reduction in most cases. Therapy management of patients following disease progression on crizotinib is also discussed. Based on available clinical data, it is evident that patients may have prolonged benefit from crizotinib after Response Evaluation Criteria in Solid Tumors-defined disease progression, and crizotinib should be continued for as long as the patient derives benefit.
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  • 文章类型: Evaluation Study
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