Τίτλος:
Single-arm, open label prospective trial to assess prediction of the role of ERCC1/XPF complex in the response of advanced NSCLC patients to platinum-based chemotherapy
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
Background: Platinum-based therapy, combined or not with immune checkpoint inhibitors, represents a front-line choice for patients with non-small-cell lung cancer (NSCLC). Despite the improved outcomes in the last years for this malignancy, only a sub-group of patients have long-term benefit. Excision repair cross-complementation group 1 (ERCC1) has been considered a potential biomarker to predict the outcome of platinum-based chemotherapy in NSCLC. However, the ERCC1 gene is transcribed in four splice variants where the isoform 202 was described as the only one active and able to complex Xeroderma pigmentosum group F-complementing protein (XPF). Here, we prospectively investigated if the active form of ERCC1, as assessed by the ERCC1/XPF complex (ERCC1/XPF), could predict the sensitivity to platinum compounds. Patients and methods: Prospectively enrolled, patients with advanced NSCLC treated with a first-line regimen containing platinum were centrally evaluated for ERCC1/XPF by a proximity ligation assay. Overall survival (OS), progression-free survival (PFS) and objective response rate (ORR) were analyzed. Results: The absence of the ERCC1/XPF in the tumor suggested a trend of worst outcomes in terms of both OS [hazard ratio (HR) 1.41, 95% confidence interval (CI) 0.67-2.94, P = 0.373] and PFS (HR 1.61, 95% CI 0.88-3.03, P = 0.123). ORR was marginally influenced in ERCC1/XPF-negative and -positive groups [odds ratio (stable disease + progressive disease versus complete response + partial response) 0.87, 95% CI 0.25-3.07, P = 0.832]. Conclusion: The lack of ERCC1/XPF complex in NSCLC tumor cells might delineate a group of patients with poor outcomes when treated with platinum compounds. ERCC1/XPF absence might well identify patients for whom a different therapeutic approach could be necessary. © 2020 The Authors
Συγγραφείς:
Ganzinelli, M.
Linardou, H.
Alvisi, M.F.
Caiola, E.
Lo Russo, G.
Cecere, F.L.
Bettini, A.C.
Psyrri, A.
Milella, M.
Rulli, E.
Fabbri, A.
De Maglie, M.
Romanelli, P.
Murray, S.
Broggini, M.
Marabese, M.
Garassino, M.C.
Λέξεις-κλειδιά:
carboplatin; cisplatin; excision repair cross complementing protein 1; gemcitabine; immunological antineoplastic agent; nucleic acid binding protein; pemetrexed; polylysine; transcription factor; tumor marker; unclassified drug; vinorelbine tartrate; Xeroderma pigmentosum group F complementing protein; DNA binding protein; endonuclease; ERCC1 protein, human; platinum, adult; advanced cancer; aged; Article; cancer chemotherapy; cancer combination chemotherapy; cancer immunotherapy; cancer survival; clinical outcome; comparative study; controlled clinical trial; controlled study; current smoker; ex-smoker; female; follow up; human; lung adenocarcinoma; major clinical study; male; multicenter study; national health organization; never smoker; non small cell lung cancer; open study; overall response rate; overall survival; prediction; progression free survival; prospective study; sensitivity and specificity; squamous cell lung carcinoma; treatment response time; genetics; lung tumor, Carcinoma, Non-Small-Cell Lung; DNA-Binding Proteins; Endonucleases; Humans; Lung Neoplasms; Platinum; Prospective Studies
DOI:
10.1016/j.esmoop.2020.100034
