吉非替尼联合贝伐单抗对比单用吉非替尼治疗突变型非鳞状非小细胞肺癌
Gefitinib Plus Bevacizumab . Gefitinib Alone for Mutant Non-squamous Non-small Cell Lung Cancer.
作者信息
Kitagawa Chiyoe, Mori Masahide, Ichiki Masao, Sukoh Noriaki, Kada Akiko, Saito Akiko M, Ichinose Yukito
机构信息
Department of Respiratory Medicine, National Hospital Organization Nagoya Medical Center, Nagoya, Japan
Department of Thoracic Oncology, National Hospital Organization Toneyama National Hospital, Toyonaka, Japan.
出版信息
In Vivo. 2019 Mar-Apr;33(2):477-482. doi: 10.21873/invivo.11498.
Abstract
BACKGROUND/AIM: A phase II trial was conducted to assess the efficacy and safety of gefitinib plus bevacizumab for EGFR mutation-positive non-small cell lung cancer (NSCLC).
PATIENTS AND METHODS
Patients were randomly assigned to receive either gefitinib at 250 mg/day alone or with bevacizumab at 15 mg/kg every 3 weeks.
RESULTS
Ten patients were allocated to the gefitinib group (group A) and 6 to the gefitinib plus bevacizumab group (group B). Median survival time (80%CI) for progression-free survival (PFS) was 15.1 months for group A, and 5.4 months for group B. Overall survival probability at 1 year (95%CI) was 0.750 for group A, and 0.667 for group B. The response rate was 44 % for group A and 50 % for group B. Adverse events occurred at a similar frequency in both groups.
CONCLUSION
PFS was shorter in group B than group A, and therefore there was no basis to proceed to a phase III trial.
摘要
背景/目的：开展一项II期试验，以评估吉非替尼联合贝伐单抗治疗表皮生长因子受体（EGFR）突变阳性的非小细胞肺癌（NSCLC）的疗效和安全性。
患者与方法
患者被随机分配，分别接受每日250毫克吉非替尼单药治疗，或每3周接受吉非替尼联合15毫克/千克贝伐单抗治疗。
结果
10例患者被分配至吉非替尼组（A组），6例患者被分配至吉非替尼联合贝伐单抗组（B组）。A组无进展生存期（PFS）的中位生存时间（80%CI）为15.1个月，B组为5.4个月。A组1年总生存概率（95%CI）为0.750，B组为0.667。A组缓解率为44%，B组为50%。两组不良事件发生频率相似。
结论
B组PFS短于A组，因此没有依据开展III期试验。
相似文献
1
Gefitinib Plus Bevacizumab . Gefitinib Alone for Mutant Non-squamous Non-small Cell Lung Cancer.吉非替尼联合贝伐单抗对比单用吉非替尼治疗突变型非鳞状非小细胞肺癌
In Vivo. 2019 Mar-Apr;33(2):477-482. doi: 10.21873/invivo.11498.
2
Rationale and Design of a Randomized Phase 2 Trial of Gefitinib Plus Bevacizumab vs Gefitinib Alone in Patients with Epidermal Growth Factor Receptor Mutant Non-Squamous Non-Small-Cell Lung Cancer: Study Protocol.吉非替尼联合贝伐单抗对比吉非替尼单药治疗表皮生长因子受体突变的非鳞状非小细胞肺癌患者的随机2期试验的原理与设计：研究方案
Kurume Med J. 2019 May 16;65(2):77-81. doi: 10.2739/kurumemedj.MS652001. Epub 2018 Nov 15.
3
EGFR-TKI rechallenge with bevacizumab in EGFR-mutant non-small cell lung cancer.表皮生长因子受体 - 酪氨酸激酶抑制剂（EGFR-TKI）联合贝伐单抗用于表皮生长因子受体（EGFR）突变的非小细胞肺癌的再挑战治疗
Cancer Chemother Pharmacol. 2015 Oct;76(4):835-41. doi: 10.1007/s00280-015-2867-8. Epub 2015 Sep 8.
4
Erlotinib alone or with bevacizumab as first-line therapy in patients with advanced non-squamous non-small-cell lung cancer harbouring EGFR mutations (JO25567): an open-label, randomised, multicentre, phase 2 study.厄洛替尼单药或联合贝伐珠单抗作为 EGFR 突变的晚期非鳞状非小细胞肺癌患者的一线治疗（JO25567）：一项开放标签、随机、多中心、Ⅱ期研究。
Lancet Oncol. 2014 Oct;15(11):1236-44. doi: 10.1016/S1470-2045(14)70381-X. Epub 2014 Aug 27.
5
Phase II trial of gefitinib in combination with bevacizumab as first-line therapy for advanced non-small cell lung cancer with activating EGFR gene mutations: the Okayama Lung Cancer Study Group Trial 1001.表皮生长因子受体基因突变阳性的晚期非小细胞肺癌患者一线应用吉非替尼联合贝伐珠单抗治疗的 II 期临床研究：冈山县肺癌研究组 1001 期临床研究
J Thorac Oncol. 2015 Mar;10(3):486-91. doi: 10.1097/JTO.0000000000000434.
6
Gefitinib plus chemotherapy versus placebo plus chemotherapy in EGFR-mutation-positive non-small-cell lung cancer after progression on first-line gefitinib (IMPRESS): a phase 3 randomised trial.吉非替尼联合化疗对比安慰剂联合化疗用于一线吉非替尼治疗后进展的 EGFR 突变阳性非小细胞肺癌（IMPRESS）：一项 3 期随机试验。
Lancet Oncol. 2015 Aug;16(8):990-8. doi: 10.1016/S1470-2045(15)00121-7. Epub 2015 Jul 6.
7
Randomized Phase II Trial of Gefitinib With and Without Pemetrexed as First-Line Therapy in Patients With Advanced Nonsquamous Non-Small-Cell Lung Cancer With Activating Epidermal Growth Factor Receptor Mutations.表皮生长因子受体激活突变的晚期非鳞状非小细胞肺癌患者一线应用吉非替尼联合或不联合培美曲塞的随机 II 期临床试验。
J Clin Oncol. 2016 Sep 20;34(27):3258-66. doi: 10.1200/JCO.2016.66.9218. Epub 2016 Aug 9.
8
Final overall survival results of WJTOG3405, a randomized phase III trial comparing gefitinib versus cisplatin with docetaxel as the first-line treatment for patients with stage IIIB/IV or postoperative recurrent EGFR mutation-positive non-small-cell lung cancer.WJTOG3405 随机 III 期临床试验的最终总生存结果，比较吉非替尼与顺铂联合多西他赛作为 IIIB/IV 期或术后复发 EGFR 突变阳性非小细胞肺癌患者的一线治疗。
Ann Oncol. 2019 Dec 1;30(12):1978-1984. doi: 10.1093/annonc/mdz399.
9
BEVERLY: Rationale and Design of a Randomized Open-Label Phase III Trial Comparing Bevacizumab Plus Erlotinib Versus Erlotinib Alone as First-Line Treatment of Patients With EGFR-Mutated Advanced Nonsquamous Non-Small-Cell Lung Cancer.贝弗利：一项随机开放标签III期试验的原理与设计，该试验比较了贝伐单抗联合厄洛替尼与单纯厄洛替尼作为表皮生长因子受体（EGFR）突变的晚期非鳞状非小细胞肺癌患者一线治疗方案的疗效。
Clin Lung Cancer. 2016 Sep;17(5):461-465. doi: 10.1016/j.cllc.2016.04.001. Epub 2016 Apr 22.
10
Gefitinib with or without Transarterial Infusion Chemotherapy (Cisplatin) for Large Nonsmall Cell Lung Cancer with Epidermal Growth Factor Receptor Mutations.表皮生长因子受体突变的大型非小细胞肺癌患者接受吉非替尼联合或不联合经动脉灌注化疗（顺铂）的效果。
J Vasc Interv Radiol. 2019 Jul;30(7):1004-1012. doi: 10.1016/j.jvir.2018.12.705. Epub 2019 Jun 4.
引用本文的文献
1
The Current State of Tumor Microenvironment-Specific Therapies for Non-Small Cell Lung Cancer.非小细胞肺癌肿瘤微环境特异性疗法的现状
Cancers (Basel). 2025 May 22;17(11):1732. doi: 10.3390/cancers17111732.
2
Dose Reduction of -TKIs for -positive Non-small Cell Lung Cancer: A Retrospective Study.针对EGFR阳性非小细胞肺癌的酪氨酸激酶抑制剂剂量减少：一项回顾性研究
Cancer Diagn Progn. 2025 Mar 3;5(2):207-215. doi: 10.21873/cdp.10431. eCollection 2025 Mar-Apr.
3
The incidence of drug-induced interstitial lung disease caused by epidermal growth factor receptor tyrosine kinase inhibitors or immune checkpoint inhibitors in patients with non-small cell lung cancer in presence and absence of vascular endothelial growth factor inhibitors: a systematic review.在有和没有血管内皮生长因子抑制剂的情况下，非小细胞肺癌患者中由表皮生长因子受体酪氨酸激酶抑制剂或免疫检查点抑制剂引起的药物性间质性肺病的发生率：一项系统评价
Front Oncol. 2024 Jun 11;14:1419256. doi: 10.3389/fonc.2024.1419256. eCollection 2024.
4
Osimertinib combined with bevacizumab as the first-line treatment in non-small cell lung cancer patients with brain metastasis harboring epidermal growth factor receptor mutations.奥希替尼联合贝伐珠单抗作为携带表皮生长因子受体突变的非小细胞肺癌脑转移患者的一线治疗。
Thorac Cancer. 2023 May;14(15):1355-1361. doi: 10.1111/1759-7714.14880. Epub 2023 Apr 5.
5
Successful neoadjuvant treatment of EGFR exon 19 deletion combined with TP53 mutation in non-small cell lung cancer using aumolertinib after osimertinib-induced myocardial damage: a case report and literature review.奥希替尼诱导心肌损伤后使用阿美替尼成功治疗 EGFR 外显子 19 缺失合并 TP53 突变的非小细胞肺癌：一例病例报告及文献复习。
Anticancer Drugs. 2023 Sep 1;34(8):954-961. doi: 10.1097/CAD.0000000000001496. Epub 2023 Jan 4.
6
Efficacy and safety of antiangiogenic agents or chemotherapy plus EGFR-TKIs in advanced non-small cell lung cancer: A systematic review and network meta-analysis.抗血管生成药物或化疗联合 EGFR-TKIs 治疗晚期非小细胞肺癌的疗效和安全性：系统评价和网络荟萃分析。
Thorac Cancer. 2023 Feb;14(6):535-543. doi: 10.1111/1759-7714.14783. Epub 2023 Jan 2.
7
Angiogenesis and epidermal growth factor receptor inhibitors in non-small cell lung cancer.非小细胞肺癌中的血管生成与表皮生长因子受体抑制剂
Explor Target Antitumor Ther. 2020;1(2):117-130. doi: 10.37349/etat.2020.00008. Epub 2020 Apr 28.
8
Impact of Smoking Status in Combination Treatment with EGFR Tyrosine Kinase Inhibitors and Anti-Angiogenic Agents in Advanced Non-Small Cell Lung Cancer Harboring Susceptible EGFR Mutations: Systematic Review and Meta-Analysis.吸烟状态对携带敏感表皮生长因子受体（EGFR）突变的晚期非小细胞肺癌患者联合使用EGFR酪氨酸激酶抑制剂和抗血管生成药物治疗的影响：系统评价与荟萃分析
J Clin Med. 2022 Jun 12;11(12):3366. doi: 10.3390/jcm11123366.
9
FAK in Cancer: From Mechanisms to Therapeutic Strategies.FAK 在癌症中的作用：从机制到治疗策略。
Int J Mol Sci. 2022 Feb 2;23(3):1726. doi: 10.3390/ijms23031726.
10
Prospects for the future of epidermal growth factor receptor-tyrosine kinase inhibitors in combination with bevacizumab.表皮生长因子受体-酪氨酸激酶抑制剂与贝伐单抗联合应用的未来前景
Transl Cancer Res. 2020 Mar;9(3):1307-1310. doi: 10.21037/tcr.2020.01.24.
本文引用的文献
1
Randomized Phase III Study Comparing Gefitinib With Erlotinib in Patients With Previously Treated Advanced Lung Adenocarcinoma: WJOG 5108L.曾接受治疗的晚期肺腺癌患者中吉非替尼对比厄洛替尼的随机 III 期研究：WJOG5108L
J Clin Oncol. 2016 Sep 20;34(27):3248-57. doi: 10.1200/JCO.2015.63.4154. Epub 2016 Mar 28.
2
Cancer incidence and incidence rates in Japan in 2009: a study of 32 population-based cancer registries for the Monitoring of Cancer Incidence in Japan (MCIJ) project.2009年日本的癌症发病率及发生率：针对日本癌症发病率监测（MCIJ）项目的32个基于人群的癌症登记处的研究。
Jpn J Clin Oncol. 2015 Sep;45(9):884-91. doi: 10.1093/jjco/hyv088. Epub 2015 Jul 3.
3
Erlotinib alone or with bevacizumab as first-line therapy in patients with advanced non-squamous non-small-cell lung cancer harbouring EGFR mutations (JO25567): an open-label, randomised, multicentre, phase 2 study.厄洛替尼单药或联合贝伐珠单抗作为 EGFR 突变的晚期非鳞状非小细胞肺癌患者的一线治疗（JO25567）：一项开放标签、随机、多中心、Ⅱ期研究。
Lancet Oncol. 2014 Oct;15(11):1236-44. doi: 10.1016/S1470-2045(14)70381-X. Epub 2014 Aug 27.
4
Erlotinib versus standard chemotherapy as first-line treatment for European patients with advanced EGFR mutation-positive non-small-cell lung cancer (EURTAC): a multicentre, open-label, randomised phase 3 trial.厄洛替尼对比标准化疗用于治疗欧洲晚期 EGFR 突变阳性非小细胞肺癌患者的一线治疗（EURTAC）：一项多中心、开放标签、随机、3 期临床试验。
Lancet Oncol. 2012 Mar;13(3):239-46. doi: 10.1016/S1470-2045(11)70393-X. Epub 2012 Jan 26.
5
Erlotinib versus chemotherapy as first-line treatment for patients with advanced EGFR mutation-positive non-small-cell lung cancer (OPTIMAL, CTONG-0802): a multicentre, open-label, randomised, phase 3 study.厄洛替尼对比化疗用于治疗晚期 EGFR 突变阳性非小细胞肺癌患者的一线治疗（OPTIMAL、CTONG-0802）：一项多中心、开放标签、随机、III 期研究。
Lancet Oncol. 2011 Aug;12(8):735-42. doi: 10.1016/S1470-2045(11)70184-X. Epub 2011 Jul 23.
6
Efficacy of bevacizumab plus erlotinib versus erlotinib alone in advanced non-small-cell lung cancer after failure of standard first-line chemotherapy (BeTa): a double-blind, placebo-controlled, phase 3 trial.贝伐珠单抗联合厄洛替尼对比厄洛替尼单药治疗标准一线化疗失败的晚期非小细胞肺癌的疗效（BeTa）：一项双盲、安慰剂对照、III 期临床试验。
Lancet. 2011 May 28;377(9780):1846-54. doi: 10.1016/S0140-6736(11)60545-X.
7
Upregulated stromal EGFR and vascular remodeling in mouse xenograft models of angiogenesis inhibitor-resistant human lung adenocarcinoma.血管生成抑制剂耐药的人肺腺癌在鼠异种移植模型中上调的基质 EGFR 和血管重塑。
J Clin Invest. 2011 Apr;121(4):1313-28. doi: 10.1172/JCI42405. Epub 2011 Mar 23.
8
First-line erlotinib and bevacizumab in patients with locally advanced and/or metastatic non-small-cell lung cancer: a phase II study including molecular imaging.一线厄洛替尼联合贝伐珠单抗治疗局部晚期和/或转移性非小细胞肺癌的Ⅱ期研究：包含分子影像学的研究。
Ann Oncol. 2011 Mar;22(3):559-566. doi: 10.1093/annonc/mdq391. Epub 2010 Aug 11.
9
Gefitinib or chemotherapy for non-small-cell lung cancer with mutated EGFR.吉非替尼或化疗用于治疗具有突变型 EGFR 的非小细胞肺癌。
N Engl J Med. 2010 Jun 24;362(25):2380-8. doi: 10.1056/NEJMoa0909530.
10
Gefitinib versus cisplatin plus docetaxel in patients with non-small-cell lung cancer harbouring mutations of the epidermal growth factor receptor (WJTOG3405): an open label, randomised phase 3 trial.吉非替尼对比顺铂联合多西他赛用于治疗表皮生长因子受体突变的非小细胞肺癌患者（WJTOG3405）：一项开放标签、随机对照 3 期临床试验。
Lancet Oncol. 2010 Feb;11(2):121-8. doi: 10.1016/S1470-2045(09)70364-X. Epub 2009 Dec 18.
Zotero 插件