[Efficacy and Safety of Crizotinib in Advanced or Recurrent ALK-positive Non-small Cell Lung Cancer].
Journal: 2019/August - Chinese Journal of Lung Cancer
ISSN: 1999-6187
Abstract:
Anaplastic lymphoma kinase (ALK) positive in non-small cell lung cancer (NSCLC) was about 5%-7% and ALK tyrosine kinase inhibitor (TKI) was the standard treatment in NSCLC. The aim of this study is to evaluate the efficacy and safety of crizotinib in patients with advanced ALK gene-positive or recurrent NSCLC.Three methods were used to screen patients with advanced or recurrent NSCLC harboring ALK gene fusion/translocation. The patients with ALK positive tested by flourescence in situ hybridization (FISH) was given orally crizotinib, 250 mg, bid. The objective response rate (ORR), progression-free survival (PFS) and safety were evaluated.A total of 226 patients were screened, 39 of whom had ALK fusion or translocation, and 37 were enrolled in the study. 35 patients were evaluated for objective response, ORR was 70.3%, and disease control rate (DCR) was 94.6%, and median PFS was 11.8 mon. The main adverse reactions were elevated transaminase (Grade 1, 91.7%), elevated transaminases (Grade 2, 23.4%), nausea (Grade 1, 75.6%), anemia (Grade 1-2, 62.3%), visual impairment (Grade 1, 21.8%), weight loss (Grade 1, 31.4%), pneumonia (Grade 2, 3.5%).Crizotinib can be used for the treatment of advanced NSCLC with ALK fusion/translocation. It is highly effective and well tolerated.
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Zhongguo Fei Ai Za Zhi 22(8): 488-493

克唑替尼治疗晚期或复发性ALK阳性非小细胞肺癌的疗效和安全性

背景与目的

间变性淋巴瘤激酶(anaplastic lymphoma kinase, ALK)基因在晚期非小细胞肺癌(non-small cell lung cancer, NSCLC)中的阳性比例约为5%-7%,ALK酪氨酸激酶抑制剂(tyrosine kinase inhibitor, TKI)为ALK阳性NSCLC患者的标准治疗。本研究拟评价克唑替尼在ALK阳性的晚期或复发性NSCLC患者中的疗效和安全性。

方法

用三种方法筛选携带ALK基因融合/倒位的晚期或复发NSCLC患者,免疫荧光原位杂交(flourescence in situ hybridization, FISH)显示阳性者给予克唑替尼口服,250 mg,2次/d。评价客观有效率(objective response rate, ORR)、无进展生存期(progression-free survival, PFS)及安全性。

结果

共筛选226例患者,其中39例出现ALK融合或倒位,37例入组,35例患者可评价客观疗效,ORR为70.3%,疾病控制率(disease control rate, DCR)为94.6%,中位PFS为11.8个月,主要不良反应为转氨酶升高(1级,91.7%)、转氨酶升高(2级,23.4%)、恶心(1级,75.6%)、贫血(1级-2级,62.3%)、视物障碍(1级,21.8%)、体重减轻(1级,31.4%)、肺炎(2级,3.5%)。

结论

克唑替尼单药可用于治疗ALK融合/倒位的晚期NSCLC患者,有效率高,耐受性较好。

Background and objective

Anaplastic lymphoma kinase (ALK) positive in non-small cell lung cancer (NSCLC) was about 5%-7% and ALK tyrosine kinase inhibitor (TKI) was the standard treatment in NSCLC. The aim of this study is to evaluate the efficacy and safety of crizotinib in patients with advanced ALK gene-positive or recurrent NSCLC.

Methods

Three methods were used to screen patients with advanced or recurrent NSCLC harboring ALK gene fusion/translocation. The patients with ALK positive tested by flourescence in situ hybridization (FISH) was given orally crizotinib, 250 mg, bid. The objective response rate (ORR), progression-free survival (PFS) and safety were evaluated.

Results

A total of 226 patients were screened, 39 of whom had ALK fusion or translocation, and 37 were enrolled in the study. 35 patients were evaluated for objective response, ORR was 70.3%, and disease control rate (DCR) was 94.6%, and median PFS was 11.8 mon. The main adverse reactions were elevated transaminase (Grade 1, 91.7%), elevated transaminases (Grade 2, 23.4%), nausea (Grade 1, 75.6%), anemia (Grade 1-2, 62.3%), visual impairment (Grade 1, 21.8%), weight loss (Grade 1, 31.4%), pneumonia (Grade 2, 3.5%).

Conclusion

Crizotinib can be used for the treatment of advanced NSCLC with ALK fusion/translocation. It is highly effective and well tolerated.

100070 北京,首都医科大学附属北京天坛医院肿瘤综合治疗病区, Department of Oncologic Comprehensive Therapy, Beijing Tiantan Hospital, Capital Medical University, Beijing 100070, China,
100071 北京,解放军总医院第五医学中心肺部肿瘤科, Department of Lung Cancer, The Fifth Medical Center, General Hospital of People's Liberation Army, Beijing 100071, China,
李 晓燕 (Xiaoyan LI): moc.621@ahrerahs; 刘 晓晴 (Xiaoqing LIU): nc.moc.liamdem@qxuil
李晓燕, Xiaoyan LI, E-mail: moc.621@ahrerahs
刘晓晴, Xiaoqing LIU, E-mail: nc.moc.liamdem@qxuil
李 晓燕 (Xiaoyan LI): moc.621@ahrerahs; 刘 晓晴 (Xiaoqing LIU): nc.moc.liamdem@qxuil
Received 2019 Jun 20; Revised 2019 Jul 21; Accepted 2019 Jul 29.

Abstract

背景与目的

间变性淋巴瘤激酶(anaplastic lymphoma kinase, ALK)基因在晚期非小细胞肺癌(non-small cell lung cancer, NSCLC)中的阳性比例约为5%-7%,ALK酪氨酸激酶抑制剂(tyrosine kinase inhibitor, TKI)为ALK阳性NSCLC患者的标准治疗。本研究拟评价克唑替尼在ALK阳性的晚期或复发性NSCLC患者中的疗效和安全性。

方法

用三种方法筛选携带ALK基因融合/倒位的晚期或复发NSCLC患者,免疫荧光原位杂交(flourescence in situ hybridization, FISH)显示阳性者给予克唑替尼口服,250 mg,2次/d。评价客观有效率(objective response rate, ORR)、无进展生存期(progression-free survival, PFS)及安全性。

结果

共筛选226例患者,其中39例出现ALK融合或倒位,37例入组,35例患者可评价客观疗效,ORR为70.3%,疾病控制率(disease control rate, DCR)为94.6%,中位PFS为11.8个月,主要不良反应为转氨酶升高(1级,91.7%)、转氨酶升高(2级,23.4%)、恶心(1级,75.6%)、贫血(1级-2级,62.3%)、视物障碍(1级,21.8%)、体重减轻(1级,31.4%)、肺炎(2级,3.5%)。

结论

克唑替尼单药可用于治疗ALK融合/倒位的晚期NSCLC患者,有效率高,耐受性较好。

Keywords: 肺肿瘤, EML4-ALK, 克唑替尼
Abstract

Abstract

Background and objective

Anaplastic lymphoma kinase (ALK) positive in non-small cell lung cancer (NSCLC) was about 5%-7% and ALK tyrosine kinase inhibitor (TKI) was the standard treatment in NSCLC. The aim of this study is to evaluate the efficacy and safety of crizotinib in patients with advanced ALK gene-positive or recurrent NSCLC.

Methods

Three methods were used to screen patients with advanced or recurrent NSCLC harboring ALK gene fusion/translocation. The patients with ALK positive tested by flourescence in situ hybridization (FISH) was given orally crizotinib, 250 mg, bid. The objective response rate (ORR), progression-free survival (PFS) and safety were evaluated.

Results

A total of 226 patients were screened, 39 of whom had ALK fusion or translocation, and 37 were enrolled in the study. 35 patients were evaluated for objective response, ORR was 70.3%, and disease control rate (DCR) was 94.6%, and median PFS was 11.8 mon. The main adverse reactions were elevated transaminase (Grade 1, 91.7%), elevated transaminases (Grade 2, 23.4%), nausea (Grade 1, 75.6%), anemia (Grade 1-2, 62.3%), visual impairment (Grade 1, 21.8%), weight loss (Grade 1, 31.4%), pneumonia (Grade 2, 3.5%).

Conclusion

Crizotinib can be used for the treatment of advanced NSCLC with ALK fusion/translocation. It is highly effective and well tolerated.

Keywords: Lung neoplasms, EML4-ALK, Crizotinib
Abstract

非小细胞肺癌(non-small cell lung cancer, NSCLC)是国内乃至全球死亡率最高的恶性肿瘤之一1],尽管5年生存率仍低于20%,但是近10年来,NSCLC的治疗有了突破性的进展,酪氨酸激酶抑制剂(tyrosine kinase inhibitors, TKIs)的出现并用于临床是其中之一。多项临床研究2-4]已经证实,表皮生长因子受体(epithelial growth factor receptor, EGFR)敏感突变型NSCLC患者接受TKIs(如吉非替尼、厄洛替尼等)治疗,其中位无进展生存期(progression-free survival, PFS)可达10个月-12个月,中位总生存期(overall survival, OS)超过36个月,可谓是“里程碑式的进步”。继EGFR-TKI之后,棘皮动物微管相关蛋白样4-间变性淋巴瘤激酶(echinoderm microtubule associated protein like 4 gene-anaplastic lymphoma kinase, EML4-ALK)融合基因的发现及ALK抑制剂(如克唑替尼)的研究是NSCLC治疗的又一重要进展。

EML4-ALK最初在淋巴瘤中发现,其2号染色体的11号外显子发生断裂,并与ALK发生重组、融合5]。陆续有报道在肺癌患者的肿瘤组织中发现ALK融合6, 7]。2009年的美国临床肿瘤协会(American Society of Clinical Oncology, ASCO)年会上,Shaw5]报告了Ⅰ期临床研究的结果:患有ALK融合或基因倒位的晚期NSCLC患者,给予ALK抑制剂——克唑替尼,其有效率达73%,中位PFS达9个月。基于这样良好的疗效和安全性,美国食品药品监督管理局(Food and Drug Administration, FDA)批准其直接进入Ⅲ期临床研究,其中A8081005研究在中国招募患者。解放军总医院第五医学中心南院区肺部肿瘤科为研究中心之一参加了005研究。本文将总结分析ALK融合患者经克唑替尼治疗后的客观有效率(objective response rate, ORR)、PFS及安全性。

Competing interests

The authors declare that they have no competing interests.

Competing interests
Competing interests

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