Bevacizumab plus chemotherapy in nonsquamous non-small cell lung cancer patients with malignant pleural effusion uncontrolled by tube drainage or pleurodesis: A phase II study North East Japan Study group trial NEJ013B.
Adenocarcinoma of Lung
/ drug therapy
Aged
Antineoplastic Combined Chemotherapy Protocols
/ therapeutic use
Bevacizumab
/ administration & dosage
Carboplatin
/ administration & dosage
Carcinoma, Non-Small-Cell Lung
/ drug therapy
Docetaxel
/ administration & dosage
Erlotinib Hydrochloride
/ administration & dosage
Female
Follow-Up Studies
Humans
Lung Neoplasms
/ drug therapy
Male
Middle Aged
Neoplasm Recurrence, Local
/ drug therapy
Pemetrexed
/ administration & dosage
Pleural Effusion, Malignant
/ complications
Pleurodesis
/ adverse effects
Prognosis
Survival Rate
Bevacizumab plus chemotherapy
non-small cell lung cancer
unsuccessful management of malignant pleural effusion
vascular endothelial growth factor
Journal
Thoracic cancer
ISSN: 1759-7714
Titre abrégé: Thorac Cancer
Pays: Singapore
ID NLM: 101531441
Informations de publication
Date de publication:
07 2020
07 2020
Historique:
received:
14
02
2020
revised:
18
04
2020
accepted:
19
04
2020
pubmed:
19
5
2020
medline:
12
3
2021
entrez:
19
5
2020
Statut:
ppublish
Résumé
Pleurodesis is the standard of care for non-small cell lung cancer (NSCLC) patients with symptomatic malignant pleural effusion (MPE). However, there is no standard management for MPE uncontrolled by pleurodesis. Most patients with unsuccessful MPE control are unable to receive effective chemotherapy. Vascular endothelial growth factor (VEGF) plays an important role in the pathogenesis of MPE. This multicenter, phase II study investigated the effects of bevacizumab plus chemotherapy in nonsquamous NSCLC patients with unsuccessful management of MPE. Nonsquamous NSCLC patients with MPE following unsuccessful tube drainage or pleurodesis received bevacizumab (15 mg/kg) plus chemotherapy every three weeks. The primary endpoint was pleural effusion control rate (PECR), defined as the percentage of patients without reaccumulation of MPE at eight weeks. Secondary endpoints included pleural progression-free survival (PPFS), safety, and quality of life (QoL). A total of 20 patients (median age: 69 years; 14 males; 20 adenocarcinomas; six epidermal growth factor receptor mutations) were enrolled in nine centers. The PECR was 80% and the primary end point was met. The PPFS and the overall survival (OS) were 16.6 months and 19.6 months, respectively. Patients with high levels of VEGF in the MPE had shorter PPFS (P = 0.010) and OS (P = 0.002). Toxicities of grade ≥ 3 included neutropenia (50%), thrombocytopenia (10%), proteinuria (10%), and hypertension (2%). The cognitive QoL score improved after treatment. Bevacizumab plus chemotherapy is highly effective with acceptable toxicities in nonsquamous NSCLC patients with uncontrolled MPE, and should be considered as a standard therapy in this setting. SIGNIFICANT FINDINGS OF THE STUDY: Bevacizumab plus chemotherapy is highly effective with acceptable toxicities in nonsquamous NSCLC patients with uncontrolled MPE. Bevacizumab plus chemotherapy should be considered as a standard treatment option for patients with uncontrolled MPE. UMIN000006868 was a phase II study of efficacy of bevacizumab plus chemotherapy for the management of malignant pleural effusion (MPE) in nonsquamous non-small cell lung cancer patients with MPE unsuccessfully controlled by tube drainage or pleurodesis (North East Japan Study Group Trial NEJ-013B) (http://umin.sc.jp/ctr/).
Sections du résumé
BACKGROUND
Pleurodesis is the standard of care for non-small cell lung cancer (NSCLC) patients with symptomatic malignant pleural effusion (MPE). However, there is no standard management for MPE uncontrolled by pleurodesis. Most patients with unsuccessful MPE control are unable to receive effective chemotherapy. Vascular endothelial growth factor (VEGF) plays an important role in the pathogenesis of MPE. This multicenter, phase II study investigated the effects of bevacizumab plus chemotherapy in nonsquamous NSCLC patients with unsuccessful management of MPE.
METHODS
Nonsquamous NSCLC patients with MPE following unsuccessful tube drainage or pleurodesis received bevacizumab (15 mg/kg) plus chemotherapy every three weeks. The primary endpoint was pleural effusion control rate (PECR), defined as the percentage of patients without reaccumulation of MPE at eight weeks. Secondary endpoints included pleural progression-free survival (PPFS), safety, and quality of life (QoL).
RESULTS
A total of 20 patients (median age: 69 years; 14 males; 20 adenocarcinomas; six epidermal growth factor receptor mutations) were enrolled in nine centers. The PECR was 80% and the primary end point was met. The PPFS and the overall survival (OS) were 16.6 months and 19.6 months, respectively. Patients with high levels of VEGF in the MPE had shorter PPFS (P = 0.010) and OS (P = 0.002). Toxicities of grade ≥ 3 included neutropenia (50%), thrombocytopenia (10%), proteinuria (10%), and hypertension (2%). The cognitive QoL score improved after treatment.
CONCLUSIONS
Bevacizumab plus chemotherapy is highly effective with acceptable toxicities in nonsquamous NSCLC patients with uncontrolled MPE, and should be considered as a standard therapy in this setting.
KEY POINTS
SIGNIFICANT FINDINGS OF THE STUDY: Bevacizumab plus chemotherapy is highly effective with acceptable toxicities in nonsquamous NSCLC patients with uncontrolled MPE.
WHAT THIS STUDY ADDS
Bevacizumab plus chemotherapy should be considered as a standard treatment option for patients with uncontrolled MPE.
CLINICAL TRIAL REGISTRATION
UMIN000006868 was a phase II study of efficacy of bevacizumab plus chemotherapy for the management of malignant pleural effusion (MPE) in nonsquamous non-small cell lung cancer patients with MPE unsuccessfully controlled by tube drainage or pleurodesis (North East Japan Study Group Trial NEJ-013B) (http://umin.sc.jp/ctr/).
Identifiants
pubmed: 32421226
doi: 10.1111/1759-7714.13472
pmc: PMC7327672
doi:
Substances chimiques
Pemetrexed
04Q9AIZ7NO
Docetaxel
15H5577CQD
Bevacizumab
2S9ZZM9Q9V
Carboplatin
BG3F62OND5
Erlotinib Hydrochloride
DA87705X9K
Types de publication
Clinical Trial, Phase II
Journal Article
Multicenter Study
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1876-1884Subventions
Organisme : Kyoto University
Pays : International
Organisme : Department of Pulmonary Medicine and Oncology, Graduate School of Medicine, Nippon Medical School
Pays : International
Organisme : Saitama Medical University
Pays : International
Informations de copyright
© 2020 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.
Références
Lung Cancer. 2016 Sep;99:131-6
pubmed: 27565928
Anticancer Res. 2016 Jun;36(6):2939-44
pubmed: 27272808
Neoplasma. 2018;65(1):132-139
pubmed: 29322797
Chest. 2005 Sep;128(3):1431-5
pubmed: 16162739
Gan To Kagaku Ryoho. 2011 Apr;38(4):524-7
pubmed: 21498978
Chest. 2005 Aug;128(2):684-9
pubmed: 16100154
Am J Pathol. 2000 Dec;157(6):1893-903
pubmed: 11106562
Med Oncol. 2013;30(3):676
pubmed: 23925664
Respirology. 2018 Jun;23(6):613-617
pubmed: 29320805
Clin Cancer Res. 1999 Nov;5(11):3364-8
pubmed: 10589746
J Clin Oncol. 2002 Nov 1;20(21):4368-80
pubmed: 12409337
Eur J Cancer. 1998 May;34(6):810-5
pubmed: 9797690
Thorax. 1999 Aug;54(8):707-10
pubmed: 10413724
Respir Med. 2008 Jul;102(7):939-48
pubmed: 18356033
Eur J Cardiothorac Surg. 2006 Dec;30(6):827-32
pubmed: 17113008
Cancer Chemother Pharmacol. 2013 Feb;71(2):457-61
pubmed: 23178954
J Clin Oncol. 2004 Apr 1;22(7):1228-33
pubmed: 15051770
BMC Pulm Med. 2015 Mar 28;15:29
pubmed: 25887349
J Biol Chem. 2016 Dec 23;291(52):26750-26761
pubmed: 27756837
Oncology. 2002;63(1):70-5
pubmed: 12187074
J Thorac Oncol. 2012 Oct;7(10):1485-9
pubmed: 22982649
Chest. 2005 Sep;128(3):1790-7
pubmed: 16162788
Chest. 2007 Sep;132(3):1036-41
pubmed: 17873197
Lung Cancer. 2010 Dec;70(3):233-46
pubmed: 20888062
Chest. 2005 Mar;127(3):909-15
pubmed: 15764775
Lung Cancer. 2007 Dec;58(3):362-8
pubmed: 17716779
Angiogenesis. 2004;7(4):335-45
pubmed: 15886877
Lung Cancer. 2011 Dec;74(3):392-5
pubmed: 21616551
EXS. 1997;79:233-69
pubmed: 9002222
Lung Cancer. 2006 Oct;54(1):51-5
pubmed: 16920219
Respirology. 2009 Nov;14(8):1188-93
pubmed: 19818055
Postgrad Med J. 2005 Nov;81(961):702-10
pubmed: 16272233
Chest. 1994 Dec;106(6 Suppl):363S-366S
pubmed: 7988265
Clin Cancer Res. 1997 Jan;3(1):47-50
pubmed: 9815536
Curr Oncol Rep. 2013 Jun;15(3):207-16
pubmed: 23568600
Eur Respir J. 2005 Apr;25(4):600-4
pubmed: 15802331