Investigation of efficacy and acquired resistance for EGFR-TKI plus bevacizumab as first-line treatment in patients with EGFR sensitive mutant non-small cell lung cancer in a Real world population.
Adenocarcinoma of Lung
/ drug therapy
Adolescent
Adult
Aged
Antineoplastic Combined Chemotherapy Protocols
/ therapeutic use
Bevacizumab
/ administration & dosage
Carcinoma, Non-Small-Cell Lung
/ drug therapy
Carcinoma, Squamous Cell
/ drug therapy
Drug Resistance, Neoplasm
/ genetics
ErbB Receptors
/ genetics
Erlotinib Hydrochloride
/ administration & dosage
Female
Follow-Up Studies
Gefitinib
/ administration & dosage
Humans
Lung Neoplasms
/ drug therapy
Male
Middle Aged
Mutation
Prognosis
Protein Kinase Inhibitors
/ pharmacology
Retrospective Studies
Survival Rate
Young Adult
Bevacizumab plus EGFR-TKI
NSCLC
PFS
Resistance mechanism
Journal
Lung cancer (Amsterdam, Netherlands)
ISSN: 1872-8332
Titre abrégé: Lung Cancer
Pays: Ireland
ID NLM: 8800805
Informations de publication
Date de publication:
03 2020
03 2020
Historique:
received:
14
07
2019
revised:
22
10
2019
accepted:
10
01
2020
pubmed:
27
1
2020
medline:
7
4
2021
entrez:
27
1
2020
Statut:
ppublish
Résumé
We aimed to investigate the clinical efficacy of EGFR tyrosine kinase inhibitor (TKI, T) plus bevacizumab (an antiangiogenic therapy, A) in a real-world population and to provide insights into their mechanism of resistance. This study included 256 NSCLC patients harboring EGFR sensitizing mutations (EGFR 19del and L858R) who underwent nextgeneration sequencing (NGS) with 168-gene panel prior to treatment between Jan 2015 to Aug 2018. Cohort A included 60 patients treated with A + T; while cohort B consisted of 120 patients treated with EGFR-TKI monotherapy with the patients identified using Propensity Score Matching (Ratio of 1:2). Clinical outcomes and potential resistance mechanism were evaluated. Baseline clinical characteristics were not significantly different between Cohort A and B. Compared with cohort B, cohort A had significantly better overall response rate (95% vs 74.2%, p = 0.001) and longer median progression-free survival (PFS, 16.5m vs.12.0 m, HR = 0.7, p = 0.001). Until Jan 2019, 31 and 103 patients in cohort A and B, respectively, were evaluated with progressive disease and underwent tissue re-biopsy and NGS profiling with 168-gene panel. In cohort B, T790M was the predominant acquired resistance mechanism, detected in 51.5% (53/103) of progressive tumors, followed by amplifications in EGFR (15.5%, 16/103) and MET (6.8%, 7/103). Contrastingly, cohort A had a significantly lower rate of T790 M mutation (35.5%, 11/31, p = 0.0003), followed by mutations in TP53 (29.0%, 9/31), RB1 (9.7%, 3/31), SMAD4 (3.2%, 1/31) and EGFR V834 L (3.2%, 1/31) and amplifications in EGFR (9.7%, 3/31), and MET(6.5%, 2/31). Treatment with first-line A + T significantly extends the time to progression and increases the response rate with acceptable safety profile. T790 M was the most common acquired resistance mechanism but it was less common in patients who received A + T.
Identifiants
pubmed: 31982639
pii: S0169-5002(20)30020-9
doi: 10.1016/j.lungcan.2020.01.009
pii:
doi:
Substances chimiques
Protein Kinase Inhibitors
0
Bevacizumab
2S9ZZM9Q9V
Erlotinib Hydrochloride
DA87705X9K
EGFR protein, human
EC 2.7.10.1
ErbB Receptors
EC 2.7.10.1
Gefitinib
S65743JHBS
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
82-88Informations de copyright
Copyright © 2020 Elsevier B.V. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of Competing Interest All authors declare no conflict of interest.