|Table of Contents|

Efficacy and safety of vascular endothelial growth factor (VEGF) inhibitors combined with tyrosine kinase inhibitors in the first-line treatment of epidermal growth factor receptor (EGFR)-mutant advanced non-small cell lung cancer

Journal Of Modern Oncology[ISSN:1672-4992/CN:61-1415/R]

Issue:
2022 06
Page:
1011-1016
Research Field:
Publishing date:

Info

Title:
Efficacy and safety of vascular endothelial growth factor (VEGF) inhibitors combined with tyrosine kinase inhibitors in the first-line treatment of epidermal growth factor receptor (EGFR)-mutant advanced non-small cell lung cancer
Author(s):
CHENG Long1; ZENG Qianglin2; DU Guobo1; GUI Yan1; LI Qiumei1; ZENG Beilei1; TAN Bangxian1; MA Daiyuan1
1.Department of Oncology,Affiliated Hospital of North Sichuan Medical College,Sichuan Nanchong 637000,China;2.Department of Respiratory Medicine,Affiliated Hospital of Chengdu University,Sichuan Chengdu 610000,China.
Keywords:
EGFR-TKI; anti-VEGF; non-small cell lung cancer; the first-line treatment; Meta-analysis
PACS:
R734.2
DOI:
10.3969/j.issn.1672-4992.2022.06.012
Abstract:
Objective:To investigate the efficacy and safety of vascular endothelial growth factor (VEGF) inhibitors combined with tyrosine kinase inhibitors (TKI) in the first-line treatment of epidermal growth factor receptor (EGFR)-mutant advanced non-small cell lung cancer (NSCLC).Methods:The efficacy and side effects of anti-VEGF drugs combined with EGFR-TKI and EGFR-TKI alone as the first-line treatment for patients with EGFR-mutant advanced NSCLC were compared.Results:This study included 5 randomized controlled trials (RCTs) involving a total of 1 230 patients with NSCLC,1 042 (85%) of whom were Asian.PFS was chosen as the primary end point,with a secondary endpoint of OS.Our results showed that the combination of EGFR-TKI with anti-VEGF drugs significantly improved PFS (HR=0.59,95%CI:0.51~0.69) compared with EGFR-TKI alone for patients with EGFR mutations,including the exon 19 deletion (HR=0.59,95%CI:0.50~0.70) and exon 21 L858R mutation (HR=0.58,95%CI:0.48~0.72).However,it did not improve OS (HR=0.93,95%CI:0.74~1.17).The more incidence of grade Ⅲ hypertension,proteinuria and rash were observed in the combination group,and the incidence of proteinuria was higher.Conclusion:The combination of EGFR-TKI with anti-VEGF drugs resulted in a significant benefit in PFS compared with EGFR-TKI alone,but it failed to provide any long-term survival benefits in patients with EGFR mutation-positive advanced NSCLC.

References:

[1]MIDHA A,DEARDEN S,MCCORMACK R.EGFR mutation incidence in non-small-cell lung cancer of adenocarcinoma histology:a systematic review and global map by ethnicity (mutMapII)［J］.Am J Cancer Res,2015,5:2892-2911.
[2]AKAMATSU H,KOH Y,OZAWA Y,et al.Osimertinib with Ramucirumab in EGFR-mutated,T790M-positive patients with progression during EGFR-TKI therapy:phase Ib study［J］.Clin Lung Cancer，2018,19(6):e871-e874.
[3]MOK TS,WU YL,AHN MJ,et al.Osimertinib or platinum-pemetrexed in EGFR T790M-positive lung cancer［J］.N Engl J Med,2017,376(7):629-640.
[4]SORIA JC,OHE Y,VANSTEENKISTE J,et al.Osimertinib in untreated EGFR-mutated advanced non-small-cell lung cancer［J］.N Engl J Med,2018,378(2):113-125.
[5]HERBST RS,ANSARI R,BUSTIN F,et al.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［J］.Lancet,2011,377(9780):1846-1854.
[6]RECKAMP KL.Targeted therapy for patients with metastatic nonsmall cell lung cancer［J］.J Natl Compr Canc Netw,2018,16:601-604.
[7]PLANCHARD D,POPAT S,KERR K,et al.Metastatic non-small cell lung cancer:ESMO clinical practice guidelines for diagnosis,treatment and follow-up［J］.Ann Oncol,2018,29(suppl 4):iv192-247.
[8]CAVANNA L,CITTERIO C,ORLANDI E.Immune checkpoint inhibitors in EGFR-mutation positive TKI-treated patients with advanced non-small-cell lung cancer network meta-analysis［J］.Oncotarget,2019，10:209-215.
[9]NAKAGAWA K,GARON EB,SETO T,et al.Ramucirumab plus erlotinib in patients with untreated,EGFR-mutated,advanced non-small-cell lung cancer (RELAY):a randomised,double-blind,placebo-controlled,phase 3 trial［J］.Lancet Oncol,2019,20(12):1655-1669.
[10]YOSHIDA K,YAMADA Y.Erlotinib alone or with bevacizumab as first-line therapy in patients with advanced non-squamous non-small-cell lung cancer harboring EGFR mutations (JO25567):an open-label,randomized,multicenter,phase II study［J］.Transl Lung Cancer Res,2015,4(3):217-219.
[11]ZHOU Q,WU YL,CHENG Y,et al.CTONG 1509:Phase III study of bevacizumab with or without erlotinib in untreated Chinese patients with advanced EGFR-mutated NSCLC［J］.Annals of Oncology,2019,30(Supplement_5):v603.
[12]SAITO H,FUKUHARA T,FURUYA N,et al.Erlotinib plus bevacizumab versus erlotinib alone in patients with EGFR-positive advanced non-squamous non-small-cell lung cancer (NEJ026):interim analysis of an open-label,randomised,multicentre,phase 3 trial［J］.Lancet Oncol,2019,20(5):625-635.
[13]STINCHCOMBE TE,JNNE PA,WANG X,et al.Effect of erlotinib plus bevacizumab vs erlotinib alone on progression-free survival in patients with advanced EGFR-mutant non-small cell lung cancer:a phase 2 randomized clinical trial ［J］.JAMA Oncol,2019,5(10):1448-1455.
[14]GRIDELLI C,ROSSI A,CIARDIELLO F,et al.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［J］.Clin Lung Cancer,2016,17(5):461-465.
[15]YU HA,SCHOENFELD AJ,MAKHNIN A,et al.Effect of osimertinib and bevacizumab on progression-free survival for patients with metastatic EGFR-mutant lung cancers:a phase 1/2 single-group open-label trial［J］.JAMA Oncol,2020,6(7):1048-1054.
[16]VILORIAPETIT A，CROMBET T，JOTHY S，et a1．Acquired resistance to the antitumor effect of epidermal growth factor receptor-blocking antibodies in vivo：a role for altered tumor angiogenesis［J］．Cancer Res J,2001，61(13)：5090-5101.
[17]WU YL,CHENG Y,ZHOU X,et al.Dacomitinib versus gefitinib as first-line treatment for patients with EGFR-mutation-positive non-small-cell lung cancer (ARCHER 1050):a randomised,open-label,phase 3 trial［J］.Lancet Oncol,2017,18(11):1454-1466.
[18]ROSELL R,CARCERENY E,GERVAIS R,et al.Spanish Lung Cancer Group in collaboration with Groupe Francais de Pneumo-Cancérologie and Associazione Italiana Oncologia Toracica: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［J］.Lancet Oncol,2012,13:239-246.
[19]DWIVEDI P,MUENCH DE,WAGNER M,et al.Phospho serine and threonine analysis of normal and mutated granulocyte colony stimulating factor receptors［J］.Scientific Data,2019,6(1):21.
[20]GRIDELLI C,CIARDIELLO F,GALLO C,et al.First-line erlotinib followed by second-line cisplatin-gemcitabine chemotherapy in advanced non-small-cell lung cancer:the TORCH randomized trial［J］.J Clin Oncol,2012,30:3002-3011.
[21]TAKESHITA J.Erlotinib plus bevacizumab is effective in EGFR-mutant NSCLC［J］.Cancer Discov,2014,4(11):OF18.

Memo

Memo:
四川省卫计委科研课题(编号：18PJ405)
Last Update: 1900-01-01