Pemetrexed-Based Chemotherapy Is Inferior to Pemetrexed-Free Regimens in Thyroid Transcription Factor 1 (TTF-1)-Negative, EGFR/ALK-Negative Lung Adenocarcinoma: A Propensity Score Matched Pairs Analysis.
Adenocarcinoma of Lung
/ drug therapy
Aged
Anaplastic Lymphoma Kinase
/ genetics
Antineoplastic Combined Chemotherapy Protocols
/ therapeutic use
Carboplatin
/ administration & dosage
Cisplatin
/ administration & dosage
DNA-Binding Proteins
/ genetics
Deoxycytidine
/ administration & dosage
ErbB Receptors
/ genetics
Female
Follow-Up Studies
Gene Rearrangement
Humans
Lung Neoplasms
/ drug therapy
Male
Matched-Pair Analysis
Middle Aged
Mutation
Pemetrexed
/ administration & dosage
Prognosis
Propensity Score
Retrospective Studies
Survival Rate
Transcription Factors
/ genetics
Gemcitabine
Non–small-cell lung cancer
Pemetrexed
Platinum-based chemotherapy
Predictive factor
Propensity-score matching
Journal
Clinical lung cancer
ISSN: 1938-0690
Titre abrégé: Clin Lung Cancer
Pays: United States
ID NLM: 100893225
Informations de publication
Date de publication:
11 2020
11 2020
Historique:
received:
17
01
2020
revised:
02
04
2020
accepted:
14
05
2020
pubmed:
6
7
2020
medline:
12
10
2021
entrez:
5
7
2020
Statut:
ppublish
Résumé
Thyroid transcription factor 1 (TTF-1) is a prognostic biomarker in lung adenocarcinoma; however, TTF-1-positive patients also display more favorable factors like actionable target mutations. In contrast, TTF-1-negative cancer is a poorly described entity. We performed a retrospective study to characterize a TTF-1-negative phenotype and to evaluate outcome depending on the chemotherapy regimen applied in the EGFR/ALK-negative population. Phenotypic traits were analyzed in 741 patients with evaluable TTF-1 expression status, among them 529 patients with platinum-based first-line chemotherapy, with disease diagnosed between 2009 and 2016 at a tertiary referral university hospital. The influence of TTF-1 and several cofactors on progression-free survival and overall survival (OS) were analyzed using a 1:1 propensity score matching model, depending on the platinum doublet chemotherapy's incorporating pemetrexed or not, with subsequent Cox regression. TTF-1 negativity implied a distinct cancer phenotype with the predominance of male sex, worse Eastern Cooperative Oncology Group performance status, greater metastatic burden at primary diagnosis, and more adrenal gland metastases. These patients had improved progression-free survival (hazard ratio, 0.42; P = .001) and OS (hazard ratio, 0.40; P < .001) when gemcitabine-, taxane-, or vinorelbine-based regimens were provided instead of pemetrexed. None of the regimens was superior in TTF-1-positive patients with regard to OS. Overall, TTF-1 expression was strongly prognostic with a substantial increase in progression-free survival (hazard ratio, 0.54; P < .001) and OS (hazard ratio, 0.53; P < .001). TTF-1 negativity is associated with a distinct cancer phenotype. Incorporation of this biomarker may be helpful when choosing an appropriate therapy regimen.
Identifiants
pubmed: 32620471
pii: S1525-7304(20)30154-6
doi: 10.1016/j.cllc.2020.05.014
pii:
doi:
Substances chimiques
DNA-Binding Proteins
0
TTF1 protein, human
0
Transcription Factors
0
Pemetrexed
04Q9AIZ7NO
Deoxycytidine
0W860991D6
Carboplatin
BG3F62OND5
ALK protein, human
EC 2.7.10.1
Anaplastic Lymphoma Kinase
EC 2.7.10.1
EGFR protein, human
EC 2.7.10.1
ErbB Receptors
EC 2.7.10.1
Cisplatin
Q20Q21Q62J
Gemcitabine
0
Types de publication
Clinical Trial
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
e607-e621Informations de copyright
Copyright © 2020 Elsevier Inc. All rights reserved.