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

Autor: Tamar Zhamurashvili, Martin Witzenrath, Matthias Brunn, Matthias Raspe, Sebastian Ochsenreither, Norbert Suttorp, Christoph Ruwwe-Glösenkamp, Frederick Klauschen, Christian Grohé, Maximilian von Laffert, Bettina Temmesfeld-Wollbrück, Nikolaj Frost
Rok vydání: 2020
Předmět:
Male
0301 basic medicine
Oncology
Cancer Research
Lung Neoplasms
Deoxycytidine
Carboplatin
0302 clinical medicine
Antineoplastic Combined Chemotherapy Protocols
Anaplastic Lymphoma Kinase
Gene Rearrangement
Hazard ratio
Middle Aged
respiratory system
Prognosis
Chemotherapy regimen
DNA-Binding Proteins
ErbB Receptors
Survival Rate
Pemetrexed
030220 oncology & carcinogenesis
Adenocarcinoma
Female
medicine.drug
Pulmonary and Respiratory Medicine
endocrine system
medicine.medical_specialty
Matched-Pair Analysis
Adenocarcinoma of Lung
03 medical and health sciences
Internal medicine
medicine
Humans
Propensity Score
Lung cancer
Aged
Retrospective Studies
Proportional hazards model
business.industry
Cancer
medicine.disease
Gemcitabine
Regimen
030104 developmental biology
Mutation
Cisplatin
business
Follow-Up Studies
Transcription Factors
Zdroj: Clinical Lung Cancer. 21:e607-e621
ISSN: 1525-7304
DOI: 10.1016/j.cllc.2020.05.014
Popis: 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.
Databáze: OpenAIRE
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